@article{LinWangMuellerRoeberetal.2005, author = {Lin, W. H. and Wang, Y. and M{\"u}ller-R{\"o}ber, Bernd and Brearley, C. A. and Xu, Z. H. and Xue, H. W.}, title = {At5PTase13 modulates cotyledon vein development through regulating auxin homeostasis}, issn = {0032-0889}, year = {2005}, abstract = {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}, language = {en} } @article{GomezMerinoBrearleyOrnatowskaetal.2004, author = {Gomez-Merino, Fernando Carlos and Brearley, C. A. and Ornatowska, Magdalena and Abdel-Haliem, Mahmoud E. F. and Zanor, Maria Ines and M{\"u}ller-R{\"o}ber, Bernd}, title = {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}, issn = {0021-9258}, year = {2004}, abstract = {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}, language = {en} } @article{XuBrearleyLinetal.2005, author = {Xu, J. and Brearley, C. A. and Lin, W. H. and Wang, Y. and Ye, R. and M{\"u}ller-R{\"o}ber, Bernd and Xu, Z. H. and Xue, H. W.}, title = {A role of Arabidopsis inositol polyphosphate kinase, AtIPK2 alpha, in pollen germination and root growth}, issn = {0032-0889}, year = {2005}, abstract = {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}, language = {en} } @article{DiluisoWalkManychetal.2021, author = {Diluiso, Francesca and Walk, Paula and Manych, Niccolo and Cerutti, Nicola and Chipiga, Vladislav and Workman, Annabelle and Ayas, Ceren and Cui, Ryna Yiyun and Cui, Diyang and Song, Kaihui and Banisch, Lucy A. and Moretti, Nikolaj and Callaghan, Max W. and Clarke, Leon and Creutzig, Felix and Hilaire, Jerome and Jotzo, Frank and Kalkuhl, Matthias and Lamb, William F. and L{\"o}schel, Andreas and M{\"u}ller-Hansen, Finn and Nemet, Gregory F. and Oei, Pao-Yu and Sovacool, Benjamin K. and Steckel, Jan Christoph and Thomas, Sebastian and Wiseman, John and Minx, Jan C.}, title = {Coal transitions - part 1}, series = {Environmental research letters}, volume = {16}, journal = {Environmental research letters}, number = {11}, publisher = {Institute of Physics Publishing (IOP)}, address = {Bristol}, issn = {1748-9326}, doi = {10.1088/1748-9326/ac1b58}, pages = {40}, year = {2021}, abstract = {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.}, language = {en} } @article{BeckerGeigerDunkeletal.2004, author = {Becker, Dirk and Geiger, D. and Dunkel, M. and Roller, A. and Bertl, Adam and Latz, A. and Carpaneto, Armando and Dietrich, Peter and Roelfsema, M. R. G. and Voelker, C. and Schmidt, D. and M{\"u}ller-R{\"o}ber, Bernd and Czempinski, Katrin and Hedrich, R.}, title = {AtTPK4, an Arabidopsis tandem-pore K+ channel, poised to control the pollen membrane voltage in a pH- and Ca2+- dependent manner}, issn = {0027-8424}, year = {2004}, abstract = {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}, language = {en} } @article{MehrabiSchulzDsouzaetal.2019, author = {Mehrabi, Pedram and Schulz, Eike C. and Dsouza, Raison and M{\"u}ller-Werkmeister, Henrike and Tellkamp, Friedjof and Miller, R. J. Dwayne and Pai, Emil F.}, title = {Time-resolved crystallography reveals allosteric communication aligned with molecular breathing}, series = {Science}, volume = {365}, journal = {Science}, number = {6458}, publisher = {American Assoc. for the Advancement of Science}, address = {Washington}, issn = {0036-8075}, doi = {10.1126/science.aaw9904}, pages = {1167 -- 1170}, year = {2019}, abstract = {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.}, language = {en} } @article{SchulzMehrabiMuellerWerkmeisteretal.2018, author = {Schulz, Eike C. and Mehrabi, Pedram and M{\"u}ller-Werkmeister, Henrike and Tellkamp, Friedjof and Jha, Ajay and Stuart, William and Persch, Elke and De Gasparo, Raoul and Diederich, Fran{\c{c}}ois and Pai, Emil F. and Miller, R. J. Dwayne}, title = {The hit-and-return system enables efficient time-resolved serial synchrotron crystallography}, series = {Nature methods : techniques for life scientists and chemists}, volume = {15}, journal = {Nature methods : techniques for life scientists and chemists}, number = {11}, publisher = {Nature Publishing Group (London)}, address = {London}, issn = {1548-7091}, doi = {10.1038/s41592-018-0180-2}, pages = {901 -- 904}, year = {2018}, abstract = {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.}, language = {en} } @article{WienholdMacriNouaillesetal.2018, author = {Wienhold, Sandra-Maria and Macri, Mario and Nouailles, Geraldine and Dietert, Kristina and Gurtner, Corinne and Gruber, Achim D. and Heimesaat, Markus M. and Lienau, Jasmin and Schumacher, Fabian and Kleuser, Burkhard and Opitz, Bastian and Suttorp, Norbert and Witzenrath, Martin and M{\"u}ller-Redetzky, Holger C.}, title = {Ventilator-induced lung injury is aggravated by antibiotic mediated microbiota depletion in mice}, series = {Critical Care}, volume = {22}, journal = {Critical Care}, number = {282}, publisher = {BMC}, address = {London}, issn = {1466-609X}, doi = {10.1186/s13054-018-2213-8}, pages = {12}, year = {2018}, abstract = {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.}, language = {en} } @article{GulbinsSchumacherBeckeretal.2018, author = {Gulbins, Anne and Schumacher, Fabian and Becker, Katrin Anne and Wilker, Barbara and Soddemann, Matthias and Boldrin, Francesco and M{\"u}ller, Christian P. and Edwards, Michael J. and Goodman, Michael and Caldwell, Charles C. and Kleuser, Burkhard and Kornhuber, Johannes and Szabo, Ildiko and Gulbins, Erich}, title = {Antidepressants act by inducing autophagy controlled by sphingomyelin-ceramide}, series = {Molecular psychiatry}, volume = {23}, journal = {Molecular psychiatry}, number = {12}, publisher = {Nature Publ. Group}, address = {London}, issn = {1359-4184}, doi = {10.1038/s41380-018-0090-9}, pages = {2324 -- 2346}, year = {2018}, abstract = {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.}, language = {en} } @misc{TrollKulkarniWangetal.2011, author = {Troll, K. and Kulkarni, Amit and Wang, W. and Darko, C. and Koumba, A. M. Bivigou and Laschewsky, Andr{\´e} and M{\"u}ller-Buschbaum, Peter and Papadakis, Christine M.}, title = {The collapse transition of poly(styrene-b-(N-isopropyl acrylamide)) diblock copolymers in aqueous solution and in thin films}, series = {Colloid and polymer science : official journal of the Kolloid-Gesellschaft}, volume = {289}, journal = {Colloid and polymer science : official journal of the Kolloid-Gesellschaft}, number = {2}, publisher = {Springer}, address = {New York}, issn = {0303-402X}, doi = {10.1007/s00396-010-2344-1}, pages = {227 -- 227}, year = {2011}, language = {en} } @article{ChristakoudiPagoniFerrarietal.2020, author = {Christakoudi, Sofia and Pagoni, Panagiota and Ferrari, Pietro and Cross, Amanda J. and Tzoulaki, Ioanna and Muller, David C. and Weiderpass, Elisabete and Freisling, Heinz and Murphy, Neil and Dossus, Laure and Turzanski Fortner, Renee and Agudo, Antonio and Overvad, Kim and Perez-Cornago, Aurora and Key, Timothy J. and Brennan, Paul and Johansson, Mattias and Tjonneland, Anne and Halkjaer, Jytte and Boutron-Ruault, Marie-Christine and Artaud, Fanny and Severi, Gianluca and Kaaks, Rudolf and Schulze, Matthias Bernd and Bergmann, Manuela M. and Masala, Giovanna and Grioni, Sara and Simeon, Vittorio and Tumino, Rosario and Sacerdote, Carlotta and Skeie, Guri and Rylander, Charlotta and Borch, Kristin Benjaminsen and Quiros, J. Ramon and Rodriguez-Barranco, Miguel and Chirlaque, Maria-Dolores and Ardanaz, Eva and Amiano, Pilar and Drake, Isabel and Stocks, Tanja and H{\"a}ggstr{\"o}m, Christel and Harlid, Sophia and Ellingjord-Dale, Merete and Riboli, Elio and Tsilidis, Konstantinos K.}, title = {Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort}, series = {International journal of cancer}, volume = {148}, journal = {International journal of cancer}, number = {7}, publisher = {Wiley}, address = {Hoboken}, issn = {0020-7136}, doi = {10.1002/ijc.33339}, pages = {1637 -- 1651}, year = {2020}, abstract = {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.}, language = {en} } @misc{ChristakoudiPagoniFerrarietal.2020, author = {Christakoudi, Sofia and Pagoni, Panagiota and Ferrari, Pietro and Cross, Amanda J. and Tzoulaki, Ioanna and Muller, David C. and Weiderpass, Elisabete and Freisling, Heinz and Murphy, Neil and Dossus, Laure and Turzanski Fortner, Renee and Agudo, Antonio and Overvad, Kim and Perez-Cornago, Aurora and Key, Timothy J. and Brennan, Paul and Johansson, Mattias and Tjonneland, Anne and Halkjaer, Jytte and Boutron-Ruault, Marie-Christine and Artaud, Fanny and Severi, Gianluca and Kaaks, Rudolf and Schulze, Matthias Bernd and Bergmann, Manuela M. and Masala, Giovanna and Grioni, Sara and Simeon, Vittorio and Tumino, Rosario and Sacerdote, Carlotta and Skeie, Guri and Rylander, Charlotta and Borch, Kristin Benjaminsen and Quiros, J. Ramon and Rodriguez-Barranco, Miguel and Chirlaque, Maria-Dolores and Ardanaz, Eva and Amiano, Pilar and Drake, Isabel and Stocks, Tanja and Haggstrom, Christel and Harlid, Sophia and Ellingjord-Dale, Merete and Riboli, Elio and Tsilidis, Konstantinos K.}, title = {Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {7}, issn = {1866-8372}, doi = {10.25932/publishup-57360}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-573609}, pages = {17}, year = {2020}, abstract = {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.}, language = {en} } @article{AichLierschVetteretal.2015, author = {Aich, Valentin and Liersch, Stefan and Vetter, Tobias and Andersson, Jafet C. M. and M{\"u}ller, Eva Nora and Hattermann, Fred}, title = {Climate or Land Use?}, series = {Water}, volume = {7}, journal = {Water}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2073-4441}, doi = {10.3390/w7062796}, pages = {2796 -- 2820}, year = {2015}, abstract = {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.}, language = {en} } @misc{AichLierschVetteretal.2017, author = {Aich, Valentin and Liersch, Stefan and Vetter, Tobias and Andersson, Jafet C. M. and M{\"u}ller, Eva Nora and Hattermann, Fred}, title = {Climate or land use?}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-400115}, pages = {25}, year = {2017}, abstract = {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.}, language = {en} } @article{VishnevetskayaHildebrandNizardoetal.2019, author = {Vishnevetskaya, Natalya S. and Hildebrand, Viet and Nizardo, Noverra Mardhatillah and Ko, Chia-Hsin and Di, Zhenyu and Radulescu, Aurel and Barnsley, Lester C. and M{\"u}ller-Buschbaum, Peter and Laschewsky, Andr{\´e} and Papadakis, Christine M.}, title = {All-in-One "Schizophrenic" self-assembly of orthogonally tuned thermoresponsive diblock copolymers}, series = {Langmuir}, volume = {35}, journal = {Langmuir}, number = {19}, publisher = {American Chemical Society}, address = {Washington}, issn = {0743-7463}, doi = {10.1021/acs.langmuir.9b00241}, pages = {6441 -- 6452}, year = {2019}, abstract = {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.}, language = {en} } @article{YangMuellerNeheretal.2006, author = {Yang, Xiaohui and M{\"u}ller, David C. and Neher, Dieter and Meerholz, Klaus}, title = {Highly efficient polymeric electrophosphorescent diodes}, year = {2006}, abstract = {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}, language = {en} } @article{ManningGossnerBossdorfetal.2015, author = {Manning, Pete and Gossner, Martin M. and Bossdorf, Oliver and Allan, Eric and Zhang, Yuan-Ye and Prati, Daniel and Bl{\"u}thgen, Nico and Boch, Steffen and B{\"o}hm, Stefan and B{\"o}rschig, Carmen and H{\"o}lzel, Norbert and Jung, Kirsten and Klaus, Valentin H. and Klein, Alexandra-Maria and Kleinebecker, Till and Krauss, Jochen and Lange, Markus and M{\"u}ller, J{\"o}rg and Pasalic, Esther and Socher, Stephanie A. and Tschapka, Marco and T{\"u}rke, Manfred and Weiner, Christiane and Werner, Michael and Gockel, Sonja and Hemp, Andreas and Renner, Swen C. and Wells, Konstans and Buscot, Francois and Kalko, Elisabeth K. V. and Linsenmair, Karl Eduard and Weisser, Wolfgang W. and Fischer, Markus}, title = {Grassland management intensification weakens the associations among the diversities of multiple plant and animal taxa}, series = {Ecology : a publication of the Ecological Society of America}, volume = {96}, journal = {Ecology : a publication of the Ecological Society of America}, number = {6}, publisher = {Wiley}, address = {Washington}, issn = {0012-9658}, doi = {10.1890/14-1307.1}, pages = {1492 -- 1501}, year = {2015}, abstract = {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.}, language = {en} } @inproceedings{HiortHugoZeinertetal.2022, author = {Hiort, Pauline and Hugo, Julian and Zeinert, Justus and M{\"u}ller, Nataniel and Kashyap, Spoorthi and Rajapakse, Jagath C. and Azuaje, Francisco and Renard, Bernhard Y. and Baum, Katharina}, title = {DrDimont: explainable drug response prediction from differential analysis of multi-omics networks}, series = {Bioinformatics}, volume = {38}, booktitle = {Bioinformatics}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1367-4803}, doi = {10.1093/bioinformatics/btac477}, pages = {ii113 -- ii119}, year = {2022}, abstract = {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.}, language = {en} }