TY - JOUR A1 - Lin, W. H. A1 - Wang, Y. A1 - Müller-Röber, Bernd A1 - Brearley, C. A. A1 - Xu, Z. H. A1 - Xue, H. W. T1 - At5PTase13 modulates cotyledon vein development through regulating auxin homeostasis N2 - Phosphatidylinositol signaling pathway and the relevant metabolites are known to be critical to the modulation of different aspects of plant growth, development, and stress responses. Inositol polyphosphate 5-phosphatase is a key enzyme involved in phosphatidylinositol metabolism and is encoded by an At5PTase gene family in Arabidopsis thaliana. A previous study shows that At5PTase11 mediates cotyledon vascular development probably through the regulation of intracellular calcium levels. In this study, we provide evidence that At5PTase13 modulates the development of cotyledon veins through its regulation of auxin homeostasis. A T-DNA insertional knockout mutant, At5pt13-1, showed a defect in development of the cotyledon vein, which was rescued completely by exogenous auxin and in part by brassinolide, a steroid hormone. Furthermore, the mutant had reduced auxin content and altered auxin accumulation in seedlings revealed by the DR5:beta-glucuronidase fusion construct in seedlings. In addition, microarray analysis shows that the transcription of key genes responsible for auxin biosynthesis and transport was altered in At5pt13-1. The At5pt13-1 mutant was also less sensitive to auxin inhibition of root elongation. These results suggest that At5PTase13 regulates the homeostasis of auxin, a key hormone controlling vascular development in plants Y1 - 2005 SN - 0032-0889 ER - TY - JOUR A1 - Gomez-Merino, Fernando Carlos A1 - Brearley, C. A. A1 - Ornatowska, Magdalena A1 - Abdel-Haliem, Mahmoud E. F. A1 - Zanor, Maria Ines A1 - Müller-Röber, Bernd T1 - AtDGK2, a novel diacylglycerol kinase from Arabidopsis thaliana, phosphorylates 1-stearoyl-2-arachidonoyl-sn- glycerol and 1,2-dioleoyl-sn-glycerol and exhibits cold-inducible gene expression N2 - Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DAG) to generate phosphatidic acid (PA). Both DAG and PA are implicated in signal transduction pathways. DGKs have been widely studied in animals, but their analysis in plants is fragmentary. Here, we report the cloning and biochemical characterization of AtDGK2, encoding DGK from Arabidopsis thaliana. AtDGK2 has a predicted molecular mass of 79.4 kDa and, like AtDGK1 previously reported, harbors two copies of a phorbol ester/DAG-binding domain in its N-terminal region. AtDGK2 belongs to a family of seven DGK genes in A. thaliana. AtDGK3 to AtDGK7 encode similar to55-kDa DGKs that lack a typical phorbol ester/DAG-binding domain. Phylogenetically, plant DGKs fall into three clusters. Members of all three clusters are widely expressed in vascular plants. Recombinant AtDGK2 was expressed in Escherichia coli and biochemically characterized. The enzyme phosphorylated 1,2-dioleoyl-sn-glycerol to yield PA, exhibiting Michaelis-Menten type kinetics. Estimated K-m and V-max values were 125 muM for DAG and 0.25 pmol of PA min(-1) mug(-1), respectively. The enzyme was maximally active at pH 7.2. Its activity was Mg2+-dependent and affected by the presence of detergents, salts, and the DGK inhibitor R59022, but not by Ca2+. AtDGK2 exhibited substrate preference for unsaturated DAG analogues (i.e. 1-stearoyl-2-arachidonoyl-sn-glycerol and 1,2- dioleoyl-sn-glycerol). The AtDGK2 gene is expressed in various tissues of the Arabidopsis plant, including leaves, roots, and flowers, as shown by Northern blot analysis and promoter-reporter gene fusions. We found that AtDGK2 is induced by exposure to low temperature (4degreesC), pointing to a role in cold signal transduction Y1 - 2004 SN - 0021-9258 ER - TY - JOUR A1 - Xu, J. A1 - Brearley, C. A. A1 - Lin, W. H. A1 - Wang, Y. A1 - Ye, R. A1 - Müller-Röber, Bernd A1 - Xu, Z. H. A1 - Xue, H. W. T1 - A role of Arabidopsis inositol polyphosphate kinase, AtIPK2 alpha, in pollen germination and root growth N2 - Inositol polyphosphates, such as inositol trisphosphate, are pivotal intracellular signaling molecules in eukaryotic cells. In higher plants the mechanism for the regulation of the type and the level of these signaling molecules is poorly understood. In this study we investigate the physiological function of an Arabidopsis (Arabidopsis thaliana) gene encoding inositol polyphosphate kinase (AtIPK2alpha), which phosphorylates inositol 1,4,5-trisphosphate successively at the D-6 and D-3 positions, and inositol 1,3,4,5-tetrakisphosphate at D-6, resulting in the generation of inositol 1,3,4,5,6-pentakisphosphate. Semiquantitative reverse transcription-PCR and promoter-beta-glucuronidase reporter gene analyses showed that AtIPK2alpha is expressed in various tissues, including roots and root hairs, stem, leaf, pollen grains, pollen tubes, the flower stigma, and siliques. Transgenic Arabidopsis plants expressing the AtIPK2alpha antisense gene under its own promoter were generated. Analysis of several independent transformants exhibiting strong reduction in AtIPK2alpha transcript levels showed that both pollen germination and pollen tube growth were enhanced in the antisense lines compared to wild-type plants, especially in the presence of nonoptimal low Ca2+ concentrations in the culture medium. Furthermore, root growth and root hair development were also stimulated in the antisense lines, in the presence of elevated external Ca2+ concentration or upon the addition of EGTA. In addition, seed germination and early seedling growth was stimulated in the antisense lines. These observations suggest a general and important role of AtIPK2alpha, and hence inositol polyphosphate metabolism, in the regulation of plant growth most likely through the regulation of calcium signaling, consistent with the well-known function of inositol trisphosphate in the mobilization of intracellular calcium stores Y1 - 2005 SN - 0032-0889 ER - TY - JOUR A1 - Diluiso, Francesca A1 - Walk, Paula A1 - Manych, Niccolo A1 - Cerutti, Nicola A1 - Chipiga, Vladislav A1 - Workman, Annabelle A1 - Ayas, Ceren A1 - Cui, Ryna Yiyun A1 - Cui, Diyang A1 - Song, Kaihui A1 - Banisch, Lucy A. A1 - Moretti, Nikolaj A1 - Callaghan, Max W. A1 - Clarke, Leon A1 - Creutzig, Felix A1 - Hilaire, Jerome A1 - Jotzo, Frank A1 - Kalkuhl, Matthias A1 - Lamb, William F. A1 - Löschel, Andreas A1 - Müller-Hansen, Finn A1 - Nemet, Gregory F. A1 - Oei, Pao-Yu A1 - Sovacool, Benjamin K. A1 - Steckel, Jan Christoph A1 - Thomas, Sebastian A1 - Wiseman, John A1 - Minx, Jan C. T1 - Coal transitions - part 1 BT - a systematic map and review of case study learnings from regional, national, and local coal phase-out experiences JF - Environmental research letters N2 - A rapid coal phase-out is needed to meet the goals of the Paris Agreement, but is hindered by serious challenges ranging from vested interests to the risks of social disruption. To understand how to organize a global coal phase-out, it is crucial to go beyond cost-effective climate mitigation scenarios and learn from the experience of previous coal transitions. Despite the relevance of the topic, evidence remains fragmented throughout different research fields, and not easily accessible. To address this gap, this paper provides a systematic map and comprehensive review of the literature on historical coal transitions. We use computer-assisted systematic mapping and review methods to chart and evaluate the available evidence on historical declines in coal production and consumption. We extracted a dataset of 278 case studies from 194 publications, covering coal transitions in 44 countries and ranging from the end of the 19th century until 2021. We find a relatively recent and rapidly expanding body of literature reflecting the growing importance of an early coal phase-out in scientific and political debates. Previous evidence has primarily focused on the United Kingdom, the United States, and Germany, while other countries that experienced large coal declines, like those in Eastern Europe, are strongly underrepresented. An increasing number of studies, mostly published in the last 5 years, has been focusing on China. Most of the countries successfully reducing coal dependency have undergone both demand-side and supply-side transitions. This supports the use of policy approaches targeting both demand and supply to achieve a complete coal phase-out. From a political economy perspective, our dataset highlights that most transitions are driven by rising production costs for coal, falling prices for alternative energies, or local environmental concerns, especially regarding air pollution. The main challenges for coal-dependent regions are structural change transformations, in particular for industry and labor. Rising unemployment is the most largely documented outcome in the sample. Policymakers at multiple levels are instrumental in facilitating coal transitions. They rely mainly on regulatory instruments to foster the transitions and compensation schemes or investment plans to deal with their transformative processes. Even though many models suggest that coal phase-outs are among the low-hanging fruits on the way to climate neutrality and meeting the international climate goals, our case studies analysis highlights the intricate political economy at work that needs to be addressed through well-designed and just policies. KW - climate change mitigation KW - coal transitions KW - evidence synthesis KW - political economy KW - systematic map Y1 - 2021 U6 - https://doi.org/10.1088/1748-9326/ac1b58 SN - 1748-9326 VL - 16 IS - 11 PB - Institute of Physics Publishing (IOP) CY - Bristol ER - TY - JOUR A1 - Becker, Dirk A1 - Geiger, D. A1 - Dunkel, M. A1 - Roller, A. A1 - Bertl, Adam A1 - Latz, A. A1 - Carpaneto, Armando A1 - Dietrich, Peter A1 - Roelfsema, M. R. G. A1 - Voelker, C. A1 - Schmidt, D. A1 - Müller-Röber, Bernd A1 - Czempinski, Katrin A1 - Hedrich, R. T1 - AtTPK4, an Arabidopsis tandem-pore K+ channel, poised to control the pollen membrane voltage in a pH- and Ca2+- dependent manner N2 - The Arabidopsis tandem-pore K+ (TPK) channels displaying four transmembrane domains and two pore regions share structural homologies with their animal counterparts of the KCNK family. In contrast to the Shaker-like Arabidopsis channels (six transmembrane domains/one pore region), the functional properties and the biological role of plant TPK channels have not been elucidated yet. Here, we show that AtTPK4 (KCO4) localizes to the plasma membrane and is predominantly expressed in pollen. AtTPK4 (KCO4) resembles the electrical properties of a voltage-independent K+ channel after expression in Xenopus oocytes and yeast. Hyperpolarizing as well as depolarizing membrane voltages elicited instantaneous K+ currents, which were blocked by extracellular calcium and cytoplasmic protons. Functional complementation assays using a K+ transport-deficient yeast confirmed the biophysical and pharmacological properties of the AtTPK4 channel. The features of AtTPK4 point toward a role in potassium homeostasis and membrane voltage control of the growing pollen tube. Thus, AtTPK4 represents a member of plant tandem-pore-K+ channels, resembling the characteristics of its animal counterparts as well as plant-specific features with respect to modulation of channel activity by acidosis and calcium Y1 - 2004 SN - 0027-8424 ER - TY - JOUR A1 - Mehrabi, Pedram A1 - Schulz, Eike C. A1 - Dsouza, Raison A1 - Müller-Werkmeister, Henrike A1 - Tellkamp, Friedjof A1 - Miller, R. J. Dwayne A1 - Pai, Emil F. T1 - Time-resolved crystallography reveals allosteric communication aligned with molecular breathing JF - Science N2 - A comprehensive understanding of protein function demands correlating structure and dynamic changes. Using time-resolved serial synchrotron crystallography, we visualized half-of-the-sites reactivity and correlated molecular-breathing motions in the enzyme fluoroacetate dehalogenase. Eighteen time points from 30 milliseconds to 30 seconds cover four turnover cycles of the irreversible reaction. They reveal sequential substrate binding, covalent-intermediate formation, setup of a hydrolytic water molecule, and product release. Small structural changes of the protein mold and variations in the number and placement of water molecules accompany the various chemical steps of catalysis. Triggered by enzyme-ligand interactions, these repetitive changes in the protein framework’s dynamics and entropy constitute crucial components of the catalytic machinery. Y1 - 2019 U6 - https://doi.org/10.1126/science.aaw9904 SN - 0036-8075 SN - 1095-9203 VL - 365 IS - 6458 SP - 1167 EP - 1170 PB - American Assoc. for the Advancement of Science CY - Washington ER - TY - JOUR A1 - Schulz, Eike C. A1 - Mehrabi, Pedram A1 - Müller-Werkmeister, Henrike A1 - Tellkamp, Friedjof A1 - Jha, Ajay A1 - Stuart, William A1 - Persch, Elke A1 - De Gasparo, Raoul A1 - Diederich, François A1 - Pai, Emil F. A1 - Miller, R. J. Dwayne T1 - The hit-and-return system enables efficient time-resolved serial synchrotron crystallography JF - Nature methods : techniques for life scientists and chemists N2 - We present a ‘hit-and-return’ (HARE) method for time-resolved serial synchrotron crystallography with time resolution from milliseconds to seconds or longer. Timing delays are set mechanically, using the regular pattern in fixed-target crystallography chips and a translation stage system. Optical pump-probe experiments to capture intermediate structures of fluoroacetate dehalogenase binding to its ligand demonstrated that data can be collected at short (30 ms), medium (752 ms) and long (2,052 ms) intervals. KW - Biophysical chemistry KW - Enzymes KW - Molecular biophysics KW - X-ray crystallography Y1 - 2018 U6 - https://doi.org/10.1038/s41592-018-0180-2 SN - 1548-7091 SN - 1548-7105 VL - 15 IS - 11 SP - 901 EP - 904 PB - Nature Publishing Group (London) CY - London ER - TY - JOUR A1 - Wienhold, Sandra-Maria A1 - Macri, Mario A1 - Nouailles, Geraldine A1 - Dietert, Kristina A1 - Gurtner, Corinne A1 - Gruber, Achim D. A1 - Heimesaat, Markus M. A1 - Lienau, Jasmin A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Opitz, Bastian A1 - Suttorp, Norbert A1 - Witzenrath, Martin A1 - Müller-Redetzky, Holger C. T1 - Ventilator-induced lung injury is aggravated by antibiotic mediated microbiota depletion in mice JF - Critical Care N2 - BackgroundAntibiotic exposure alters the microbiota, which can impact the inflammatory immune responses. Critically ill patients frequently receive antibiotic treatment and are often subjected to mechanical ventilation, which may induce local and systemic inflammatory responses and development of ventilator-induced lung injury (VILI). The aim of this study was to investigate whether disruption of the microbiota by antibiotic therapy prior to mechanical ventilation affects pulmonary inflammatory responses and thereby the development of VILI.MethodsMice underwent 6-8weeks of enteral antibiotic combination treatment until absence of cultivable bacteria in fecal samples was confirmed. Control mice were housed equally throughout this period. VILI was induced 3 days after completing the antibiotic treatment protocol, by high tidal volume (HTV) ventilation (34ml/kg; positive end-expiratory pressure=2 cmH(2)O) for 4h. Differences in lung function, oxygenation index, pulmonary vascular leakage, macroscopic assessment of lung injury, and leukocyte and lymphocyte differentiation were assessed. Control groups of mice ventilated with low tidal volume and non-ventilated mice were analyzed accordingly.ResultsAntibiotic-induced microbiota depletion prior to HTV ventilation led to aggravation of VILI, as shown by increased pulmonary permeability, increased oxygenation index, decreased pulmonary compliance, enhanced macroscopic lung injury, and increased cytokine/chemokine levels in lung homogenates.ConclusionsDepletion of the microbiota by broad-spectrum antibiotics prior to HTV ventilation renders mice more susceptible to developing VILI, which could be clinically relevant for critically ill patients frequently receiving broad-spectrum antibiotics. KW - Broad-spectrum antibiotic therapy KW - Ventilator-induced lung injury KW - Microbiota Y1 - 2018 U6 - https://doi.org/10.1186/s13054-018-2213-8 SN - 1466-609X SN - 1364-8535 VL - 22 IS - 282 PB - BMC CY - London ER - TY - JOUR A1 - Gulbins, Anne A1 - Schumacher, Fabian A1 - Becker, Katrin Anne A1 - Wilker, Barbara A1 - Soddemann, Matthias A1 - Boldrin, Francesco A1 - Müller, Christian P. A1 - Edwards, Michael J. A1 - Goodman, Michael A1 - Caldwell, Charles C. A1 - Kleuser, Burkhard A1 - Kornhuber, Johannes A1 - Szabo, Ildiko A1 - Gulbins, Erich T1 - Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide JF - Molecular psychiatry N2 - Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days. Y1 - 2018 U6 - https://doi.org/10.1038/s41380-018-0090-9 SN - 1359-4184 SN - 1476-5578 VL - 23 IS - 12 SP - 2324 EP - 2346 PB - Nature Publ. Group CY - London ER - TY - GEN A1 - Troll, K. A1 - Kulkarni, Amit A1 - Wang, W. A1 - Darko, C. A1 - Koumba, A. M. Bivigou A1 - Laschewsky, André A1 - Müller-Buschbaum, Peter A1 - Papadakis, Christine M. T1 - The collapse transition of poly(styrene-b-(N-isopropyl acrylamide)) diblock copolymers in aqueous solution and in thin films T2 - Colloid and polymer science : official journal of the Kolloid-Gesellschaft Y1 - 2011 U6 - https://doi.org/10.1007/s00396-010-2344-1 SN - 0303-402X VL - 289 IS - 2 SP - 227 EP - 227 PB - Springer CY - New York ER - TY - JOUR A1 - Christakoudi, Sofia A1 - Pagoni, Panagiota A1 - Ferrari, Pietro A1 - Cross, Amanda J. A1 - Tzoulaki, Ioanna A1 - Muller, David C. A1 - Weiderpass, Elisabete A1 - Freisling, Heinz A1 - Murphy, Neil A1 - Dossus, Laure A1 - Turzanski Fortner, Renee A1 - Agudo, Antonio A1 - Overvad, Kim A1 - Perez-Cornago, Aurora A1 - Key, Timothy J. A1 - Brennan, Paul A1 - Johansson, Mattias A1 - Tjonneland, Anne A1 - Halkjaer, Jytte A1 - Boutron-Ruault, Marie-Christine A1 - Artaud, Fanny A1 - Severi, Gianluca A1 - Kaaks, Rudolf A1 - Schulze, Matthias Bernd A1 - Bergmann, Manuela M. A1 - Masala, Giovanna A1 - Grioni, Sara A1 - Simeon, Vittorio A1 - Tumino, Rosario A1 - Sacerdote, Carlotta A1 - Skeie, Guri A1 - Rylander, Charlotta A1 - Borch, Kristin Benjaminsen A1 - Quiros, J. Ramon A1 - Rodriguez-Barranco, Miguel A1 - Chirlaque, Maria-Dolores A1 - Ardanaz, Eva A1 - Amiano, Pilar A1 - Drake, Isabel A1 - Stocks, Tanja A1 - Häggström, Christel A1 - Harlid, Sophia A1 - Ellingjord-Dale, Merete A1 - Riboli, Elio A1 - Tsilidis, Konstantinos K. T1 - Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort JF - International journal of cancer N2 - Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood. KW - BMI change KW - cancer KW - middle adulthood KW - weight gain KW - weight loss Y1 - 2020 U6 - https://doi.org/10.1002/ijc.33339 SN - 0020-7136 SN - 1097-0215 VL - 148 IS - 7 SP - 1637 EP - 1651 PB - Wiley CY - Hoboken ER - TY - GEN A1 - Christakoudi, Sofia A1 - Pagoni, Panagiota A1 - Ferrari, Pietro A1 - Cross, Amanda J. A1 - Tzoulaki, Ioanna A1 - Muller, David C. A1 - Weiderpass, Elisabete A1 - Freisling, Heinz A1 - Murphy, Neil A1 - Dossus, Laure A1 - Turzanski Fortner, Renee A1 - Agudo, Antonio A1 - Overvad, Kim A1 - Perez-Cornago, Aurora A1 - Key, Timothy J. A1 - Brennan, Paul A1 - Johansson, Mattias A1 - Tjonneland, Anne A1 - Halkjaer, Jytte A1 - Boutron-Ruault, Marie-Christine A1 - Artaud, Fanny A1 - Severi, Gianluca A1 - Kaaks, Rudolf A1 - Schulze, Matthias Bernd A1 - Bergmann, Manuela M. A1 - Masala, Giovanna A1 - Grioni, Sara A1 - Simeon, Vittorio A1 - Tumino, Rosario A1 - Sacerdote, Carlotta A1 - Skeie, Guri A1 - Rylander, Charlotta A1 - Borch, Kristin Benjaminsen A1 - Quiros, J. Ramon A1 - Rodriguez-Barranco, Miguel A1 - Chirlaque, Maria-Dolores A1 - Ardanaz, Eva A1 - Amiano, Pilar A1 - Drake, Isabel A1 - Stocks, Tanja A1 - Haggstrom, Christel A1 - Harlid, Sophia A1 - Ellingjord-Dale, Merete A1 - Riboli, Elio A1 - Tsilidis, Konstantinos K. T1 - Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1373 KW - BMI change KW - cancer KW - middle adulthood KW - weight gain KW - weight loss Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-573609 SN - 1866-8372 IS - 7 ER - TY - JOUR A1 - Aich, Valentin A1 - Liersch, Stefan A1 - Vetter, Tobias A1 - Andersson, Jafet C. M. A1 - Müller, Eva Nora A1 - Hattermann, Fred T1 - Climate or Land Use? BT - Attribution of Changes in River Flooding in the Sahel Zone JF - Water N2 - This study intends to contribute to the ongoing discussion on whether land use and land cover changes (LULC) or climate trends have the major influence on the observed increase of flood magnitudes in the Sahel. A simulation-based approach is used for attributing the observed trends to the postulated drivers. For this purpose, the ecohydrological model SWIM (Soil and Water Integrated Model) with a new, dynamic LULC module was set up for the Sahelian part of the Niger River until Niamey, including the main tributaries Sirba and Goroul. The model was driven with observed, reanalyzed climate and LULC data for the years 1950-2009. In order to quantify the shares of influence, one simulation was carried out with constant land cover as of 1950, and one including LULC. As quantitative measure, the gradients of the simulated trends were compared to the observed trend. The modeling studies showed that for the Sirba River only the simulation which included LULC was able to reproduce the observed trend. The simulation without LULC showed a positive trend for flood magnitudes, but underestimated the trend significantly. For the Goroul River and the local flood of the Niger River at Niamey, the simulations were only partly able to reproduce the observed trend. In conclusion, the new LULC module enabled some first quantitative insights into the relative influence of LULC and climatic changes. For the Sirba catchment, the results imply that LULC and climatic changes contribute in roughly equal shares to the observed increase in flooding. For the other parts of the subcatchment, the results are less clear but show, that climatic changes and LULC are drivers for the flood increase; however their shares cannot be quantified. Based on these modeling results, we argue for a two-pillar adaptation strategy to reduce current and future flood risk: Flood mitigation for reducing LULC-induced flood increase, and flood adaptation for a general reduction of flood vulnerability. Y1 - 2015 U6 - https://doi.org/10.3390/w7062796 SN - 2073-4441 VL - 7 IS - 6 SP - 2796 EP - 2820 PB - MDPI CY - Basel ER - TY - GEN A1 - Aich, Valentin A1 - Liersch, Stefan A1 - Vetter, Tobias A1 - Andersson, Jafet C. M. A1 - Müller, Eva Nora A1 - Hattermann, Fred T1 - Climate or land use? BT - Attribution of changes in river flooding in the Sahel Zone N2 - This study intends to contribute to the ongoing discussion on whether land use and land cover changes (LULC) or climate trends have the major influence on the observed increase of flood magnitudes in the Sahel. A simulation-based approach is used for attributing the observed trends to the postulated drivers. For this purpose, the ecohydrological model SWIM (Soil and Water Integrated Model) with a new, dynamic LULC module was set up for the Sahelian part of the Niger River until Niamey, including the main tributaries Sirba and Goroul. The model was driven with observed, reanalyzed climate and LULC data for the years 1950–2009. In order to quantify the shares of influence, one simulation was carried out with constant land cover as of 1950, and one including LULC. As quantitative measure, the gradients of the simulated trends were compared to the observed trend. The modeling studies showed that for the Sirba River only the simulation which included LULC was able to reproduce the observed trend. The simulation without LULC showed a positive trend for flood magnitudes, but underestimated the trend significantly. For the Goroul River and the local flood of the Niger River at Niamey, the simulations were only partly able to reproduce the observed trend. In conclusion, the new LULC module enabled some first quantitative insights into the relative influence of LULC and climatic changes. For the Sirba catchment, the results imply that LULC and climatic changes contribute in roughly equal shares to the observed increase in flooding. For the other parts of the subcatchment, the results are less clear but show, that climatic changes and LULC are drivers for the flood increase; however their shares cannot be quantified. Based on these modeling results, we argue for a two-pillar adaptation strategy to reduce current and future flood risk: Flood mitigation for reducing LULC-induced flood increase, and flood adaptation for a general reduction of flood vulnerability. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 345 KW - simulation-based attribution KW - Sahel KW - Niger River KW - climate variability KW - hydrological modeling KW - flood mitigation KW - flood adaptation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-400115 ER - TY - JOUR A1 - Vishnevetskaya, Natalya S. A1 - Hildebrand, Viet A1 - Nizardo, Noverra Mardhatillah A1 - Ko, Chia-Hsin A1 - Di, Zhenyu A1 - Radulescu, Aurel A1 - Barnsley, Lester C. A1 - Müller-Buschbaum, Peter A1 - Laschewsky, André A1 - Papadakis, Christine M. T1 - All-in-One "Schizophrenic" self-assembly of orthogonally tuned thermoresponsive diblock copolymers JF - Langmuir N2 - Smart, fully orthogonal switching was realized in a highly biocompatible diblock copolymer system with variable trigger-induced aqueous self-assembly. The polymers are composed of nonionic and zwitterionic blocks featuring lower and upper critical solution temperatures (LCSTs and UCSTs). In the system investigated, diblock copolymers from poly(N-isopropyl methacrylamide) (PNIPMAM) and a poly(sulfobetaine methacrylamide), systematic variation of the molar mass of the latter block allowed for shifting the UCST of the latter above the LCST of the PNIPMAM block in a salt-free condition. Thus, successive thermal switching results in "schizophrenic" micellization, in which the roles of the hydrophobic core block and the hydrophilic shell block are interchanged depending on the temperature. Furthermore, by virtue of the strong electrolyte-sensitivity of the zwitterionic polysulfobetaine block, we succeeded to shift its UCST below the LCST of the PNIPMAM block by adding small amounts of an electrolyte, thus inverting the pathway of switching. This superimposed orthogonal switching by electrolyte addition enabled us to control the switching scenarios between the two types of micelles (i) via an insoluble state, if the LCST-type cloud point is below the UCST-type cloud point, which is the case at low salt concentrations or (ii) via a molecularly dissolved state, if the LCST-type cloud point is above the UCST-type cloud point, which is the case at high salt concentrations. Systematic variation of the block lengths allowed for verifying the anticipated behavior and identifying the molecular architecture needed. The versatile and tunable self-assembly offers manifold opportunities, for example, for smart emulsifiers or for sophisticated carrier systems. Y1 - 2019 U6 - https://doi.org/10.1021/acs.langmuir.9b00241 SN - 0743-7463 VL - 35 IS - 19 SP - 6441 EP - 6452 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Yang, Xiaohui A1 - Müller, David C. A1 - Neher, Dieter A1 - Meerholz, Klaus T1 - Highly efficient polymeric electrophosphorescent diodes N2 - Polymeric electrophosphorescent LEDs with internal quantum efficiencies approaching unity have been fabricated. Such performance levels are previously unknown for OLEDs. The key to this success is redox chemically doped oxetane- crosslinkable hole-transporting layers with multilayer capability (see figure). They improve hole injection and act as electron-blocking layers, without the need to include exciton-or hole-blocking layers Y1 - 2006 UR - 1960 = DOI: 10.1002/adma.200501867 ER - TY - JOUR A1 - Manning, Pete A1 - Gossner, Martin M. A1 - Bossdorf, Oliver A1 - Allan, Eric A1 - Zhang, Yuan-Ye A1 - Prati, Daniel A1 - Blüthgen, Nico A1 - Boch, Steffen A1 - Böhm, Stefan A1 - Börschig, Carmen A1 - Hölzel, Norbert A1 - Jung, Kirsten A1 - Klaus, Valentin H. A1 - Klein, Alexandra-Maria A1 - Kleinebecker, Till A1 - Krauss, Jochen A1 - Lange, Markus A1 - Müller, Jörg A1 - Pasalic, Esther A1 - Socher, Stephanie A. A1 - Tschapka, Marco A1 - Türke, Manfred A1 - Weiner, Christiane A1 - Werner, Michael A1 - Gockel, Sonja A1 - Hemp, Andreas A1 - Renner, Swen C. A1 - Wells, Konstans A1 - Buscot, Francois A1 - Kalko, Elisabeth K. V. A1 - Linsenmair, Karl Eduard A1 - Weisser, Wolfgang W. A1 - Fischer, Markus T1 - Grassland management intensification weakens the associations among the diversities of multiple plant and animal taxa JF - Ecology : a publication of the Ecological Society of America N2 - Land-use intensification is a key driver of biodiversity change. However, little is known about how it alters relationships between the diversities of different taxonomic groups, which are often correlated due to shared environmental drivers and trophic interactions. Using data from 150 grassland sites, we examined how land-use intensification (increased fertilization, higher livestock densities, and increased mowing frequency) altered correlations between the species richness of 15 plant, invertebrate, and vertebrate taxa. We found that 54% of pairwise correlations between taxonomic groups were significant and positive among all grasslands, while only one was negative. Higher land-use intensity substantially weakened these correlations(35% decrease in rand 43% fewer significant pairwise correlations at high intensity), a pattern which may emerge as a result of biodiversity declines and the breakdown of specialized relationships in these conditions. Nevertheless, some groups (Coleoptera, Heteroptera, Hymenoptera and Orthoptera) were consistently correlated with multidiversity, an aggregate measure of total biodiversity comprised of the standardized diversities of multiple taxa, at both high and lowland-use intensity. The form of intensification was also important; increased fertilization and mowing frequency typically weakened plant-plant and plant-primary consumer correlations, whereas grazing intensification did not. This may reflect decreased habitat heterogeneity under mowing and fertilization and increased habitat heterogeneity under grazing. While these results urge caution in using certain taxonomic groups to monitor impacts of agricultural management on biodiversity, they also suggest that the diversities of some groups are reasonably robust indicators of total biodiversity across a range of conditions. KW - Biodiversity indicators KW - correlation KW - fertilization KW - grassland management KW - grazing KW - land-use change KW - land-use intensity KW - mowing KW - multidiversity KW - multitrophic interactions Y1 - 2015 U6 - https://doi.org/10.1890/14-1307.1 SN - 0012-9658 SN - 1939-9170 VL - 96 IS - 6 SP - 1492 EP - 1501 PB - Wiley CY - Washington ER - TY - CHAP A1 - Hiort, Pauline A1 - Hugo, Julian A1 - Zeinert, Justus A1 - Müller, Nataniel A1 - Kashyap, Spoorthi A1 - Rajapakse, Jagath C. A1 - Azuaje, Francisco A1 - Renard, Bernhard Y. A1 - Baum, Katharina T1 - DrDimont: explainable drug response prediction from differential analysis of multi-omics networks T2 - Bioinformatics N2 - Motivation: While it has been well established that drugs affect and help patients differently, personalized drug response predictions remain challenging. Solutions based on single omics measurements have been proposed, and networks provide means to incorporate molecular interactions into reasoning. However, how to integrate the wealth of information contained in multiple omics layers still poses a complex problem. Results: We present DrDimont, Drug response prediction from Differential analysis of multi-omics networks. It allows for comparative conclusions between two conditions and translates them into differential drug response predictions. DrDimont focuses on molecular interactions. It establishes condition-specific networks from correlation within an omics layer that are then reduced and combined into heterogeneous, multi-omics molecular networks. A novel semi-local, path-based integration step ensures integrative conclusions. Differential predictions are derived from comparing the condition-specific integrated networks. DrDimont's predictions are explainable, i.e. molecular differences that are the source of high differential drug scores can be retrieved. We predict differential drug response in breast cancer using transcriptomics, proteomics, phosphosite and metabolomics measurements and contrast estrogen receptor positive and receptor negative patients. DrDimont performs better than drug prediction based on differential protein expression or PageRank when evaluating it on ground truth data from cancer cell lines. We find proteomic and phosphosite layers to carry most information for distinguishing drug response. Y1 - 2022 U6 - https://doi.org/10.1093/bioinformatics/btac477 SN - 1367-4803 SN - 1367-4811 VL - 38 SP - ii113 EP - ii119 PB - Oxford Univ. Press CY - Oxford ER -