@article{HoehnJerniganJaptoketal.2017, author = {Hoehn, Richard S. and Jernigan, Peter L. and Japtok, Lukasz and Chang, Alex L. and Midura, Emily F. and Caldwell, Charles C. and Kleuser, Burkhard and Lentsch, Alex B. and Edwards, Michael J. and Gulbins, Erich and Pritts, Timothy A.}, title = {Acid sphingomyelinase inhibition in stored erythrocytes reduces transfusion-associated lung inflammation}, series = {Annals of surgery : a monthly review of surgical science and practice}, volume = {265}, journal = {Annals of surgery : a monthly review of surgical science and practice}, number = {1}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0003-4932}, doi = {10.1097/SLA.0000000000001648}, pages = {218 -- 226}, year = {2017}, abstract = {Objective: We aimed to identify the role of the enzyme acid sphingomyelinase in the aging of stored units of packed red blood cells (pRBCs) and subsequent lung inflammation after transfusion. Summary Background Data: Large volume pRBC transfusions are associated with multiple adverse clinical sequelae, including lung inflammation. Microparticles are formed in stored pRBCs over time and have been shown to contribute to lung inflammation after transfusion. Methods: Human and murine pRBCs were stored with or without amitriptyline, a functional inhibitor of acid sphingomyelinase, or obtained from acid sphingomyelinase-deficient mice, and lung inflammation was studied in mice receiving transfusions of pRBCs and microparticles isolated from these units. Results: Acid sphingomyelinase activity in pRBCs was associated with the formation of ceramide and the release of microparticles. Treatment of pRBCs with amitriptyline inhibited acid sphingomyelinase activity, ceramide accumulation, and microparticle production during pRBC storage. Transfusion of aged pRBCs or microparticles isolated from aged blood into mice caused lung inflammation. This was attenuated after transfusion of pRBCs treated with amitriptyline or from acid sphingomyelinase-deficient mice. Conclusions: Acid sphingomyelinase inhibition in stored pRBCs offers a novel mechanism for improving the quality of stored blood.}, language = {en} } @phdthesis{Hochrein2017, author = {Hochrein, Lena}, title = {Development of a new DNA-assembly method and its application for the establishment of a red light-sensing regulation system}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-404441}, school = {Universit{\"a}t Potsdam}, pages = {146}, year = {2017}, abstract = {In der hier vorgelegten Doktorarbeit wurde eine Strategie zur schnellen, einfachen und zuverl{\"a}ssigen Assemblierung von DNS-Fragmenten, genannt AssemblX, entwickelt. Diese kann genutzt werden, um komplexe DNS-Konstrukte, wie beispielsweise komplette Biosynthesewege, aufzubauen. Dies dient der Produktion von technisch oder medizinisch relevanten Produkten in biotechnologisch nutzbaren Organismen. Die Vorteile der Klonierungsstrategie liegen in der Schnelligkeit der Klonierung, der Flexibilit{\"a}t bez{\"u}glich des Wirtsorganismus, sowie der hohen Effektivit{\"a}t, die durch gezielte Optimierung erreicht wurde. Die entwickelte Technik erlaubt die nahtlose Assemblierung von Genfragmenten und bietet eine Komplettl{\"o}sung von der Software-gest{\"u}tzten Planung bis zur Fertigstellung von DNS-Konstrukten, welche die Gr{\"o}ße von Mini-Chromosomen erreichen k{\"o}nnen. Mit Hilfe der oben beschriebenen AssemblX Strategie wurde eine optogenetische Plattform f{\"u}r die B{\"a}ckerhefe Saccharomyces cerevisiae etabliert. Diese besteht aus einem Rotlicht-sensitiven Photorezeptor und seinem interagierenden Partner aus Arabidopsis thaliana, welche in lichtabh{\"a}ngiger Weise miteinander agieren. Diese Interaktion wurde genutzt, um zwei Rotlicht-aktivierbare Proteine zu erstellen: Einen Transkriptionsfaktor, der nach Applikation eines Lichtpulses die Produktion eines frei w{\"a}hlbaren Proteins stimuliert, sowie eine Cre Rekombinase, die ebenfalls nach Bestrahlung mit einer bestimmten Wellenl{\"a}nge die zufallsbasierte Reorganisation bestimmter DNS-Konstrukte erm{\"o}glicht. Zusammenfassend wurden damit drei Werkzeuge f{\"u}r die synthetische Biologie etabliert. Diese erm{\"o}glichen den Aufbau von komplexen Biosynthesewegen, deren Licht-abh{\"a}ngige Regulation, sowie die zufallsbasierte Rekombination zu Optimierungszwecken.}, language = {en} } @article{HeunischChaykovskavonEinemetal.2017, author = {Heunisch, Fabian and Chaykovska, Lyubov and von Einem, Gina and Alter, Markus and Dschietzig, Thomas and Kretschmer, Axel and Kellner, Karl-Heinz and Hocher, Berthold}, title = {ADMA predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus undergoing coronary angiography}, series = {Medicine}, volume = {96}, journal = {Medicine}, number = {6}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0025-7974}, doi = {10.1097/MD.0000000000006065}, pages = {7}, year = {2017}, abstract = {Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide (NO)-synthase and a biomarker of endothelial dysfunction (ED). ED plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of our study was to evaluate serum ADMA concentration as a biomarker of an acute renal damage during the follow-up of 90 days after contrast medium (CM) application. Blood samples were obtained from 330 consecutive patients with diabetes mellitus or mild renal impairment immediately before, 24 and 48 hours after the CM application for coronary angiography. The patients were followed for 90 days. The composite endpoints were major adverse renal events (MARE) defined as occurrence of death, initiation of dialysis, or a doubling of serum creatinine concentration. Overall, ADMA concentration in plasma increased after CM application, although, there was no differences between ADMA levels in patients with and without CIN. ADMA concentration 24 hours after the CM application was predictive for dialysis with a specificity of 0.889 and sensitivity of 0.653 at values higher than 0.71 mu mol/L (area under the curve: 0.854, 95\% confidential interval: 0.767-0.941, P<0.001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. 24 hours after the CM application, ADMA concentration in plasma was predictive for MARE with a specificity of 0.833 and sensitivity of 0.636 at a value of more than 0.70 mu mol/L (area under the curve: 0.750, 95\% confidence interval: 0.602-0.897, P=0.004). Multivariate logistic regression analysis confirmed that ADMA and anemia were significant predictors of MARE. Further analysis revealed that increased ADMA concentration in plasma was highly significant predictor of MARE in patients with CIN. Moreover, patients with CIN and MARE had the highest plasma ADMA levels 24 hours after CM exposure in our study cohort. The impact of ADMA on MARE was independent of such known CIN risk factors as anemia, pre-existing renal failure, pre-existing heart failure, and diabetes. ADMA concentration in plasma is a promising novel biomarker of major contrast-induced nephropathy-associated events 90 days after contrast media exposure.}, language = {en} } @phdthesis{Hethey2017, author = {Hethey, Christoph Philipp}, title = {Cell physiology based pharmacodynamic modeling of antimicrobial drug combinations}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-401056}, school = {Universit{\"a}t Potsdam}, pages = {102}, year = {2017}, abstract = {Mathematical models of bacterial growth have been successfully applied to study the relationship between antibiotic drug exposure and the antibacterial effect. Since these models typically lack a representation of cellular processes and cell physiology, the mechanistic integration of drug action is not possible on the cellular level. The cellular mechanisms of drug action, however, are particularly relevant for the prediction, analysis and understanding of interactions between antibiotics. Interactions are also studied experimentally, however, a lacking consent on the experimental protocol hinders direct comparison of results. As a consequence, contradictory classifications as additive, synergistic or antagonistic are reported in literature. In the present thesis we developed a novel mathematical model for bacterial growth that integrates cell-level processes into the population growth level. The scope of the model is to predict bacterial growth under antimicrobial perturbation by multiple antibiotics in vitro. To this end, we combined cell-level data from literature with population growth data for Bacillus subtilis, Escherichia coli and Staphylococcus aureus. The cell-level data described growth-determining characteristics of a reference cell, including the ribosomal concentration and efficiency. The population growth data comprised extensive time-kill curves for clinically relevant antibiotics (tetracycline, chloramphenicol, vancomycin, meropenem, linezolid, including dual combinations). The new cell-level approach allowed for the first time to simultaneously describe single and combined effects of the aforementioned antibiotics for different experimental protocols, in particular different growth phases (lag and exponential phase). Consideration of ribosomal dynamics and persisting sub-populations explained the decreased potency of linezolid on cultures in the lag phase compared to exponential phase cultures. The model captured growth rate dependent killing and auto-inhibition of meropenem and - also for vancomycin exposure - regrowth of the bacterial cultures due to adaptive resistance development. Stochastic interaction surface analysis demonstrated the pronounced antagonism between meropenem and linezolid to be robust against variation in the growth phase and pharmacodynamic endpoint definition, but sensitive to a change in the experimental duration. Furthermore, the developed approach included a detailed representation of the bacterial cell-cycle. We used this representation to describe septation dynamics during the transition of a bacterial culture from the exponential to stationary growth phase. Resulting from a new mechanistic understanding of transition processes, we explained the lag time between the increase in cell number and bacterial biomass during the transition from the lag to exponential growth phase. Furthermore, our model reproduces the increased intracellular RNA mass fraction during long term exposure of bacteria to chloramphenicol. In summary, we contribute a new approach to disentangle the impact of drug effects, assay readout and experimental protocol on antibiotic interactions. In the absence of a consensus on the corresponding experimental protocols, this disentanglement is key to translate information between heterogeneous experiments and also ultimately to the clinical setting.}, language = {en} } @misc{HerdeEccard2017, author = {Herde, Antje and Eccard, Jana}, title = {Consistency in boldness, activity and exploration at different stages of life}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-401395}, pages = {10}, year = {2017}, abstract = {Background: Animals show consistent individual behavioural patterns over time and over situations. This phenomenon has been referred to as animal personality or behavioural syndromes. Little is known about consistency of animal personalities over entire life times. We investigated the repeatability of behaviour in common voles (Microtus arvalis) at different life stages, with different time intervals, and in different situations. Animals were tested using four behavioural tests in three experimental groups: 1. before and after maturation over three months, 2. twice as adults during one week, and 3. twice as adult animals over three months, which resembles a substantial part of their entire adult life span of several months. Results: Different behaviours were correlated within and between tests and a cluster analysis showed three possible behavioural syndrome-axes, which we name boldness, exploration and activity. Activity and exploration behaviour in all tests was highly repeatable in adult animals tested over one week. In animals tested over maturation, exploration behaviour was consistent whereas activity was not. Voles that were tested as adults with a three-month interval showed the opposite pattern with stable activity but unstable exploration behaviour. Conclusions: The consistency in behaviour over time suggests that common voles do express stable personality over short time. Over longer periods however, behaviour is more flexible and depending on life stage (i.e. tested before/after maturation or as adults) of the tested individual. Level of boldness or activity does not differ between tested groups and maintenance of variation in behavioural traits can therefore not be explained by expected future assets as reported in other studies.}, language = {en} } @misc{HenzeRailaKempfetal.2017, author = {Henze, Andrea and Raila, Jens and Kempf, Caroline and Reinke, Petra and Sefrin, Anett and Querfeld, Uwe and Schweigert, Florian J.}, title = {Vitamin A metabolism is changed in donors after living-kidney transplantation}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-400942}, pages = {7}, year = {2017}, abstract = {Background The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT. Results As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months. Conclusion LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors.}, language = {en} } @misc{HentrichTauerEspanoletal.2017, author = {Hentrich, Doreen and Tauer, Klaus and Espanol, Montserrat and Ginebra, Maria-Pau and Taubert, Andreas}, title = {EDTA and NTA effectively tune the mineralization of calcium phosphate from bulk aqueous solution}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1095}, issn = {1866-8372}, doi = {10.25932/publishup-46918}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-469186}, pages = {23}, year = {2017}, abstract = {This study describes the effects of nitrilotriacetic acid (NTA) and ethylenediaminotetraacetic acid (EDTA) on themineralization of calciumphosphate from bulk aqueous solution. Mineralization was performed between pH 6 and 9 and with NTA or EDTA concentrations of 0, 5, 10, and 15 mM. X-ray diffraction and infrared spectroscopy show that at low pH, mainly brushite precipitates and at higher pH, mostly hydroxyapatite forms. Both additives alter the morphology of the precipitates. Without additive, brushite precipitates as large plates. With NTA, the morphology changes to an unusual rod-like shape. With EDTA, the edges of the particles are rounded and disk-like particles form. Conductivity and pH measurements suggest that the final products form through several intermediate steps.}, language = {en} } @article{HenkelColemanSchraplauetal.2017, author = {Henkel, Janin and Coleman, Charles Dominic and Schraplau, Anne and J{\"o}hrens, Korinna and Weber, Daniela and Castro, Jose Pedro and Hugo, Martin and Schulz, Tim Julius and Kr{\"a}mer, Stephanie and Sch{\"u}rmann, Annette and P{\"u}schel, Gerhard Paul}, title = {Induction of Steatohepatitis (NASH) with Insulin Resistance in Wild-type B6 Mice by a Western-type Diet Containing Soybean Oil and Cholesterol}, series = {Molecular medicine}, volume = {23}, journal = {Molecular medicine}, publisher = {Feinstein Inst. for Medical Research}, address = {Manhasset}, issn = {1076-1551}, doi = {10.2119/molmed.2016.00203}, pages = {70 -- 82}, year = {2017}, abstract = {Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of the metabolic syndrome. Many currently used animal models of NAFLD/NASH lack clinical features of either NASH or metabolic syndrome such as hepatic inflammation and fibrosis (e.g., high-fat diets) or overweight and insulin resistance (e.g., methionine-choline-deficient diets), or they are based on monogenetic defects (e.g., ob/ob mice). In the current study, a Western-type diet containing soybean oil with high n-6-PUFA and 0.75\% cholesterol (SOD + Cho) induced steatosis, inflammation and fibrosis accompanied by hepatic lipid peroxidation and oxidative stress in livers of C57BL/6-mice, which in addition showed increased weight gain and insulin resistance, thus displaying a phenotype closely resembling all clinical features of NASH in patients with metabolic syndrome. In striking contrast, a soybean oil-containing Western-type diet without cholesterol (SOD) induced only mild steatosis but not hepatic inflammation, fibrosis, weight gain or insulin resistance. Another high-fat diet, mainly consisting of lard and supplemented with fructose in drinking water (LAD + Fru), resulted in more prominent weight gain, insulin resistance and hepatic steatosis than SOD + Cho, but livers were devoid of inflammation and fibrosis. Although both LAD + Fru-and SOD + Cho-fed animals had high plasma cholesterol, liver cholesterol was elevated only in SOD + Cho animals. Cholesterol induced expression of chemotactic and inflammatory cytokines in cultured Kupffer cells and rendered hepatocytes more susceptible to apoptosis. In summary, dietary cholesterol in the SOD + Cho diet may trigger hepatic inflammation and fibrosis. SOD + Cho-fed animals may be a useful disease model displaying many clinical features of patients with the metabolic syndrome and NASH.}, language = {en} } @misc{HempelKoseskaNikoloskietal.2017, author = {Hempel, Sabrina and Koseska, Aneta and Nikoloski, Zoran and Kurths, J{\"u}rgen}, title = {Unraveling gene regulatory networks from time-resolved gene expression data}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-400924}, pages = {26}, year = {2017}, abstract = {Background: Inferring regulatory interactions between genes from transcriptomics time-resolved data, yielding reverse engineered gene regulatory networks, is of paramount importance to systems biology and bioinformatics studies. Accurate methods to address this problem can ultimately provide a deeper insight into the complexity, behavior, and functions of the underlying biological systems. However, the large number of interacting genes coupled with short and often noisy time-resolved read-outs of the system renders the reverse engineering a challenging task. Therefore, the development and assessment of methods which are computationally efficient, robust against noise, applicable to short time series data, and preferably capable of reconstructing the directionality of the regulatory interactions remains a pressing research problem with valuable applications. Results: Here we perform the largest systematic analysis of a set of similarity measures and scoring schemes within the scope of the relevance network approach which are commonly used for gene regulatory network reconstruction from time series data. In addition, we define and analyze several novel measures and schemes which are particularly suitable for short transcriptomics time series. We also compare the considered 21 measures and 6 scoring schemes according to their ability to correctly reconstruct such networks from short time series data by calculating summary statistics based on the corresponding specificity and sensitivity. Our results demonstrate that rank and symbol based measures have the highest performance in inferring regulatory interactions. In addition, the proposed scoring scheme by asymmetric weighting has shown to be valuable in reducing the number of false positive interactions. On the other hand, Granger causality as well as information-theoretic measures, frequently used in inference of regulatory networks, show low performance on the short time series analyzed in this study. Conclusions: Our study is intended to serve as a guide for choosing a particular combination of similarity measures and scoring schemes suitable for reconstruction of gene regulatory networks from short time series data. We show that further improvement of algorithms for reverse engineering can be obtained if one considers measures that are rooted in the study of symbolic dynamics or ranks, in contrast to the application of common similarity measures which do not consider the temporal character of the employed data. Moreover, we establish that the asymmetric weighting scoring scheme together with symbol based measures (for low noise level) and rank based measures (for high noise level) are the most suitable choices.}, language = {en} } @phdthesis{Heise2017, author = {Heise, Janine}, title = {Phylogenetic and physiological characterization of deep-biosphere microorganisms in El'gygytgyn Crater Lake sediments}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-403436}, school = {Universit{\"a}t Potsdam}, pages = {117}, year = {2017}, abstract = {The existence of diverse and active microbial ecosystems in the deep subsurface - a biosphere that was originally considered devoid of life - was discovered in multiple microbiological studies. However, most of the studies are restricted to marine ecosystems, while our knowledge about the microbial communities in the deep subsurface of lake systems and their potentials to adapt to changing environmental conditions is still fragmentary. This doctoral thesis aims to build up a unique data basis for providing the first detailed high-throughput characterization of the deep biosphere of lacustrine sediments and to emphasize how important it is to differentiate between the living and the dead microbial community in deep biosphere studies. In this thesis, up to 3.6 Ma old sediments (up to 317 m deep) of the El'gygytgyn Crater Lake were examined, which represents the oldest terrestrial climate record of the Arctic. Combining next generation sequencing with detailed geochemical characteristics and other environmental parameters, the microbial community composition was analyzed in regard to changing climatic conditions within the last 3.6 Ma to 1.0 Ma (Pliocene and Pleistocene). DNA from all investigated sediments was successfully extracted and a surprisingly diverse (6,910 OTUs) and abundant microbial community in the El'gygytgyn deep sediments were revealed. The bacterial abundance (10³-10⁶ 16S rRNA copies g⁻¹ sediment) was up to two orders of magnitudes higher than the archaeal abundance (10¹-10⁵) and fluctuates with the Pleistocene glacial/interglacial cyclicality. Interestingly, a strong increase in the microbial diversity with depth was observed (approximately 2.5 times higher diversity in Pliocene sediments compared to Pleistocene sediments). The increase in diversity with depth in the Lake El'gygytgyn is most probably caused by higher sedimentary temperatures towards the deep sediment layers as well as an enhanced temperature-induced intra-lake bioproductivity and higher input of allochthonous organic-rich material during Pliocene climatic conditions. Moreover, the microbial richness parameters follow the general trends of the paleoclimatic parameters, such as the paleo-temperature and paleo-precipitation. The most abundant bacterial representatives in the El'gygytgyn deep biosphere are affiliated with the phyla Proteobacteria, Actinobacteria, Bacteroidetes, and Acidobacteria, which are also commonly distributed in the surrounding permafrost habitats. The predominated taxon was the halotolerant genus Halomonas (in average 60\% of the total reads per sample). Additionally, this doctoral thesis focuses on the live/dead differentiation of microbes in cultures and environmental samples. While established methods (e.g., fluorescence in situ hybridization, RNA analyses) are not applicable to the challenging El'gygytgyn sediments, two newer methods were adapted to distinguish between DNA from live cells and free (extracellular, dead) DNA: the propidium monoazide (PMA) treatment and the cell separation adapted for low amounts of DNA. The applicability of the DNA-intercalating dye PMA was successfully evaluated to mask free DNA of different cultures of methanogenic archaea, which play a major role in the global carbon cycle. Moreover, an optimal procedure to simultaneously treat bacteria and archaea was developed using 130 µM PMA and 5 min of photo-activation with blue LED light, which is also applicable on sandy environmental samples with a particle load of ≤ 200 mg mL⁻¹. It was demonstrated that the soil texture has a strong influence on the PMA treatment in particle-rich samples and that in particular silt and clay-rich samples (e.g., El'gygytgyn sediments) lead to an insufficient shielding of free DNA by PMA. Therefore, a cell separation protocol was used to distinguish between DNA from live cells (intracellular DNA) and extracellular DNA in the El'gygytgyn sediments. While comparing these two DNA pools with a total DNA pool extracted with a commercial kit, significant differences in the microbial composition of all three pools (mean distance of relative abundance: 24.1\%, mean distance of OTUs: 84.0\%) was discovered. In particular, the total DNA pool covers significantly fewer taxa than the cell-separated DNA pools and only inadequately represents the living community. Moreover, individual redundancy analyses revealed that the microbial community of the intra- and extracellular DNA pool are driven by different environmental factors. The living community is mainly influenced by life-dependent parameters (e.g., sedimentary matrix, water availability), while the extracellular DNA is dependent on the biogenic silica content. The different community-shaping parameters and the fact, that a redundancy analysis of the total DNA pool explains significantly less variance of the microbial community, indicate that the total DNA represents a mixture of signals of the live and dead microbial community. This work provides the first fundamental data basis of the diversity and distribution of microbial deep biosphere communities of a lake system over several million years. Moreover, it demonstrates the substantial importance of extracellular DNA in old sediments. These findings may strongly influence future environmental community analyses, where applications of live/dead differentiation avoid incorrect interpretations due to a failed extraction of the living microbial community or an overestimation of the past community diversity in the course of total DNA extraction approaches.}, language = {en} } @article{HeinzeJoshi2017, author = {Heinze, Johannes and Joshi, Jasmin Radha}, title = {Plant-soil feedback effects can be masked by aboveground herbivory under natural field conditions}, series = {Oecologia}, volume = {186}, journal = {Oecologia}, number = {1}, publisher = {Springer}, address = {New York}, issn = {0029-8549}, doi = {10.1007/s00442-017-3997-y}, pages = {235 -- 246}, year = {2017}, abstract = {For plants, herbivory and interactions with their surrounding soil ecosystem are crucial factors influencing individual performance and plant-community composition. Until now, research has mostly focused on individual effects of herbivory or plant-soil feedbacks (PSFs) on plant growth and community composition, but few studies have explicitly investigated herbivory in the context of PSFs. These few studies, however, were performed under greenhouse conditions even though PSFs and herbivory may differ between greenhouse and field conditions. Therefore, we performed a field experiment in a grassland, testing the growth responses of three grass species that consistently differ in local abundance, on soils previously conditioned by these species. We tested these PSF effects for the three species both in the presence and in the absence of aboveground herbivores. Without herbivores, the two subdominant species suffered from negative PSF effects. However, in the presence of herbivores and on heterospecific soils, the same two species experienced a significant loss of shoot biomass, whereas, in contrast, enhanced root growth was observed on conspecific soils, resulting in overall neutral PSF effects. The dominant species was not damaged by herbivores and showed overall neutral PSF effects in the field with and without herbivores. Our study provides empirical evidence that negative PSF effects that exist under natural field conditions in grasslands can be overwhelmed by aboveground herbivory. Hence, potential PSF effects might not be detected in the field, because other abiotic and biotic interactions such as aboveground herbivory have stronger effects on plant performance and might therefore mask or override these PSF effects.}, language = {en} } @article{HeimTrenseSokolovaetal.2017, author = {Heim, Wieland and Trense, Daronja and Sokolova, Galina V. and Kitagawa, Tamaki}, title = {Increased populations of endangered cranes after Amur River flood}, series = {Waterbirds}, volume = {40}, journal = {Waterbirds}, publisher = {Waterbirds SOC}, address = {Washington}, issn = {1524-4695}, doi = {10.1675/063.040.0309}, pages = {282 -- 288}, year = {2017}, abstract = {Dam construction on the Zeya River, which is an important tributary of the Amur River in Far East Russia, has caused significant declines in water levels and frequency of floods in the adjacent floodplains since 1980. However, an extreme flood event occurred in 2013. Populations of six crane species were monitored before and after these drastic water level changes at Muraviovka Park in Far East Russia, an important breeding and stop-over site. Individuals were counted by territory mapping during the breeding season (2000-2015) and by roosting site counts during autumn migration (2006-2015). The objective of this study was to evaluate whether changes in water levels had a significant impact on local and migratory crane populations. We found a positive effect of flooding on numbers of breeding Red-crowned Cranes (Grus japonensis) and White-naped Cranes (Antigone vipio), as well as on numbers of roosting Hooded Cranes (Grus monacha) in autumn. Siberian Cranes (Leucogeranus leucogeranus) were only observed after the wetlands were flooded. The results of this study highlight the importance of elevated Amur River water levels for crane populations of global importance.}, language = {en} } @article{HeimLenskiSchulzeetal.2017, author = {Heim, Olga and Lenski, Johannes and Schulze, Jelena and Jung, Kirsten and Kramer-Schadt, Stephanie and Eccard, Jana and Voigt, Christian C.}, title = {The relevance of vegetation structures and small water bodies for bats foraging above farmland}, series = {Basic and applied ecology : Journal of the Gesellschaft f{\"u}r {\"O}kologie}, volume = {27}, journal = {Basic and applied ecology : Journal of the Gesellschaft f{\"u}r {\"O}kologie}, publisher = {Elsevier GMBH}, address = {M{\"u}nchen}, issn = {1439-1791}, doi = {10.1016/j.baae.2017.12.001}, pages = {9 -- 19}, year = {2017}, abstract = {Bats are known to forage and commute close to vegetation structures when moving across the agricultural matrix, but the role of isolated landscape elements in arable fields for bat activity is unknown. Therefore, we investigated the influence of small isolated ponds which lie within arable fields close to vegetation structures on the flight and foraging activity of bats. Additionally, we compared species-specific activity measures between forest edges and linear structures such as hedgerows. We repeatedly recorded bat activity using passive acoustic monitoring along 20 transects extending from the vegetation edge up to 200 m into the arable field (hereafter: edge-field interface) with a small pond present at five transects per edge type (linear vs. forest). Using generalized linear mixed effect models, we analyzed the effects of edge type, pond presence and the season on species-specific flight and foraging activity within the edge-field interface. We found a higher flight activity of Nyctalus noctula and Pipistrellus pygmaeus above the arable field when a pond was present. Furthermore, Pipistrellus nathusii and Pipistrellus pipistrellus foraged more frequently at forest edges than at linear structures (e.g. hedgerows). Additionally, we found three major patterns of seasonal variation in the activity of bats along the edge-field interface. This study highlights the species-specific and dynamic use of forest and hedgerow or tree line edges by bats and their importance for different bat species in the agricultural landscape. Further, additional landscape elements such as small isolated ponds within arable fields might support the activity of bats above the open agricultural landscape, thereby facilitating agroecosystem functioning. Therefore, additional landscape elements within managed areas should be restored and protected against the conversion into arable land and better linked to surrounding landscape elements in order to efficiently support bats within the agroecosystem.}, language = {en} } @phdthesis{Heim2017, author = {Heim, Olga}, title = {Spatiotemporal effects on bat activity above intensively managed farmland}, school = {Universit{\"a}t Potsdam}, pages = {ii, 150}, year = {2017}, abstract = {Intakte und widerstandsf{\"a}hige {\"O}kosysteme sind essenziell f{\"u}r die Aufrechterhaltung optimaler Lebensbedingungen f{\"u}r das Leben auf der Erde. Die Basis f{\"u}r solche {\"O}kosysteme bilden intakte {\"o}kologische Wechselwirkungen zwischen einer Vielzahl von Arten. Durch den beispiellosen Verlust der Biodiversit{\"a}t, welcher durch die in der zweiten H{\"a}lfte des 20. Jahrhunderts zunehmende Intensivierung der Agrarwirtschaft und die Zerst{\"o}rung und Fragmentierung von Habitaten hervorgerufen wurde, k{\"o}nnen {\"o}kologische Wechselwirkungen und damit die Funktionsf{\"a}higkeit von Agrar{\"o}kosystemen stark eingeschr{\"a}nkt werden. Um den R{\"u}ckgang der Biodiversit{\"a}t in Agrar{\"o}kosystemen abschw{\"a}chen zu k{\"o}nnen, m{\"u}ssen wir die {\"o}kologischen Wechselwirkungen in Agrar{\"o}kosystemen besser verstehen. Hierbei spielen Flederm{\"a}use eine besondere Rolle, weil sie verschiedenste {\"o}kologische Nischen besetzen und eine Reihe von {\"O}kosystemleistungen erf{\"u}llen so wie z.B. die Kontrolle von Sch{\"a}dlingspopulationen in Agrarlandschaften. {\"U}berdies tr{\"a}gt die Ordnung der Flederm{\"a}use (Chiroptera) betr{\"a}chtlich zur globalen Diversit{\"a}t der S{\"a}ugetiere bei. Obwohl viele Fledermauspopulationen durch die Intensivierung der Agrarwirtschaft dezimiert wurden, ist noch relativ wenig dar{\"u}ber bekannt wie unterschiedliche Fledermausarten die offene Agrarlandschaft nutzen. Dieses Wissen ist jedoch essenziell f{\"u}r den Schutz von Fledermausarten in intensiv bewirtschafteten Agrarlandschaften und dringend notwendig besonders vor dem Hintergrund der vorhergesagten erweiterten Ausweitung der intensiven Agrarwirtschaft. Zus{\"a}tzlich werden Flederm{\"a}use durch den zuletzt massiven Ausbau von Windkraftanlagen, welche f{\"u}r viele Vogel- und Fledermausarten ein erh{\"o}htes T{\"o}tungsrisiko darstellen, bedroht. Das Ziel dieser Dissertation war es deshalb, die Einfl{\"u}sse ausgew{\"a}hlter raum-zeitlicher Faktoren auf die artspezifische Fledermausaktivit{\"a}t {\"u}ber intensiv genutzten Agrarfl{\"a}chen in einer von Agrarwirtschaft dominierten Landschaft zu untersuchen. Dazu habe ich die Fledermausaktivit{\"a}t mittels passiver akustischer Echoortungsaufnahme in den Jahren 2012 bis 2014 auf insgesamt 113 Untersuchungsfl{\"a}chen in offenen Ackerfl{\"a}chen im Nordosten Brandenburgs erfasst. Die Echoortungsrufe in etwa 27.779 Aufnahmen habe ich manuell bis auf die Art bestimmt und die berechneten artspezifischen Aktivit{\"a}tsparameter mit Hilfe von komplexen statistischen Verfahren untersucht. Im ersten Kapitel dieser Arbeit, habe ich die berechneten Aktivit{\"a}tsparameter von {\"o}kologisch unterschiedlichen Fledermausgruppen auf saisonale Muster hin untersucht. Dabei war ich besonders an Unterschieden zu den bekannten saisonalen Aktivit{\"a}tsmustern in naturnahen Habitaten interessiert. Im zweiten Kapitel dieser Arbeit, habe ich den Einfluss von linearen Geh{\"o}lzstrukturen am Feldrand und von kleinen Wasserfl{\"a}chen (S{\"o}llen) innerhalb von Ackerfl{\"a}chen auf die Flug- und Jagdaktivit{\"a}t verschiedener Fledermausarten {\"u}ber diesen Fl{\"a}chen untersucht. Zus{\"a}tzlich war ich daran interessiert, ob sich etwaige Effekte dieser Landschaftselemente auf die Fledermausaktivit{\"a}t im Laufe des Jahres ver{\"a}ndern. Im dritten Kapitel dieser Arbeit war es mein Ziel den Zusammenhang zwischen unterschiedlichen r{\"a}umlichen und zeitlichen Einfl{\"u}ssen auf die artspezifische Fledermausaktivit{\"a}t {\"u}ber offenen Agrarfl{\"a}chen zu untersuchen. Dabei habe ich meine Untersuchungen auf Faktoren fokussiert, die daf{\"u}r bekannt sind Fledermausaktivit{\"a}t zu beeinflussen, wie z.B. Faktoren auf kleinr{\"a}umiger Skala, die mit der Beuteverf{\"u}gbarkeit zusammenh{\"a}ngen, und verschiedene Landschaftscharakteristika auf großr{\"a}umiger Skala. Auf der zeitlichen Skala, habe ich mich auf den Einfluss der Saison konzentriert. Zusammenfassend heben die Ergebnisse dieser Arbeit die Wichtigkeit naturnaher Landschaftselemente f{\"u}r die Fledermausaktivit{\"a}t {\"u}ber Agrarfl{\"a}chen hervor. Allerdings war nicht nur die Landschaftsstruktur f{\"u}r die Fledermausaktivit{\"a}t {\"u}ber Ackerfl{\"a}chen ausschlaggebend, sondern auch der Einfluss von interaktiven Effekten zwischen z.B. Landschaftscharakteristika und der lokalen Beuteverf{\"u}gbarkeit. Ein weiteres Kernergebnis ist die saisonale Variabilit{\"a}t des Einflusses der Landschaftsstruktur auf die Fledermausaktivit{\"a}t. Hierbei hatten bestimmte Landschaftselemente vor allem im Sommer einen großen Einfluss auf die Fledermausaktivit{\"a}t. Das Potenzial der {\"O}kosystemleistung durch spezifische Fledermausarten, welches wiederholt in den unterschiedlichen Kapiteln hervorgehoben wurde, ist ein weiteres Kernergebnis. Da die Fledermausaktivit{\"a}t jedoch stark von der Landschaftsstruktur in der Umgebung abh{\"a}ngt, ist es wichtig diese fledermausfreundlich zu gestalten, um die {\"O}kosystemleistung der Sch{\"a}dlingskontrolle {\"u}ber Agrarfl{\"a}chen nutzen zu k{\"o}nnen. Schlussendlich tr{\"a}gt diese Arbeit in ihrer Gesamtheit zum bestehenden Wissen {\"u}ber die Fledermausbiologie und -{\"o}kologie bei und verdeutlicht die komplexen Wechselwirkungen unterschiedlicher Einfl{\"u}sse auf mehreren raum-zeitlichen Ebenen. Die Ergebnisse dieser Arbeit k{\"o}nnen als Basis zur Verbesserung und Entwicklung von Schutzmaßnahmen f{\"u}r Flederm{\"a}use in intensiv genutzten Agrarlandschaften dienen. Da Flederm{\"a}use als gute Bioindikatoren gelten, k{\"o}nnen effektive Schutzmaßnahmen f{\"u}r Flederm{\"a}use auch zum Schutz anderer Arten beitragen und damit potenziell den weiteren Verlust der Biodiversit{\"a}t in Agrarlandschaften abschw{\"a}chen.}, language = {en} } @misc{HasanHocher2017, author = {Hasan, Ahmed Abdallah Abdalrahman Mohamed and Hocher, Berthold}, title = {Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy}, series = {Journal of Molecular Endocrinology}, volume = {59}, journal = {Journal of Molecular Endocrinology}, publisher = {Bioscientifica LTD}, address = {Bristol}, issn = {0952-5041}, doi = {10.1530/JME-17-0005}, pages = {R1 -- R10}, year = {2017}, abstract = {Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membranebound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure-and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.}, language = {en} } @misc{HartungBenaryWolfetal.2017, author = {Hartung, Niklas and Benary, Uwe and Wolf, Jana and Kofahl, Bente}, title = {Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf in wild-type and mutant hepatocytes}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {886}, issn = {1866-8372}, doi = {10.25932/publishup-43077}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-430778}, pages = {18}, year = {2017}, abstract = {Background Cells are able to communicate and coordinate their function within tissues via secreted factors. Aberrant secretion by cancer cells can modulate this intercellular communication, in particular in highly organised tissues such as the liver. Hepatocytes, the major cell type of the liver, secrete Dickkopf (Dkk), which inhibits Wnt/ β-catenin signalling in an autocrine and paracrine manner. Consequently, Dkk modulates the expression of Wnt/ β-catenin target genes. We present a mathematical model that describes the autocrine and paracrine regulation of hepatic gene expression by Dkk under wild-type conditions as well as in the presence of mutant cells. Results Our spatial model describes the competition of Dkk and Wnt at receptor level, intra-cellular Wnt/ β-catenin signalling, and the regulation of target gene expression for 21 individual hepatocytes. Autocrine and paracrine regulation is mediated through a feedback mechanism via Dkk and Dkk diffusion along the porto-central axis. Along this axis an APC concentration gradient is modelled as experimentally detected in liver. Simulations of mutant cells demonstrate that already a single mutant cell increases overall Dkk concentration. The influence of the mutant cell on gene expression of surrounding wild-type hepatocytes is limited in magnitude and restricted to hepatocytes in close proximity. To explore the underlying molecular mechanisms, we perform a comprehensive analysis of the model parameters such as diffusion coefficient, mutation strength and feedback strength. Conclusions Our simulations show that Dkk concentration is elevated in the presence of a mutant cell. However, the impact of these elevated Dkk levels on wild-type hepatocytes is confined in space and magnitude. The combination of inter- and intracellular processes, such as Dkk feedback, diffusion and Wnt/ β-catenin signal transduction, allow wild-type hepatocytes to largely maintain their gene expression.}, language = {en} } @article{HansenMeyerFerrarietal.2017, author = {Hansen, Bjoern Oest and Meyer, Etienne H. and Ferrari, Camilla and Vaid, Neha and Movahedi, Sara and Vandepoele, Klaas and Nikoloski, Zoran and Mutwil, Marek}, title = {Ensemble gene function prediction database reveals genes important for complex I formation in Arabidopsis thaliana}, series = {New phytologist : international journal of plant science}, volume = {217}, journal = {New phytologist : international journal of plant science}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {0028-646X}, doi = {10.1111/nph.14921}, pages = {1521 -- 1534}, year = {2017}, abstract = {Recent advances in gene function prediction rely on ensemble approaches that integrate results from multiple inference methods to produce superior predictions. Yet, these developments remain largely unexplored in plants. We have explored and compared two methods to integrate 10 gene co-function networks for Arabidopsis thaliana and demonstrate how the integration of these networks produces more accurate gene function predictions for a larger fraction of genes with unknown function. These predictions were used to identify genes involved in mitochondrial complex I formation, and for five of them, we confirmed the predictions experimentally. The ensemble predictions are provided as a user-friendly online database, EnsembleNet. The methods presented here demonstrate that ensemble gene function prediction is a powerful method to boost prediction performance, whereas the EnsembleNet database provides a cutting-edge community tool to guide experimentalists.}, language = {en} } @article{HahnMeyerSchroeteretal.2017, author = {Hahn, Marc Benjamin and Meyer, Susann and Schr{\"o}ter, Maria-Astrid and Seitz, Harald and Kunte, Hans-J{\"o}rg and Solomun, Tihomir and Sturm, Heinz}, title = {Direct electron irradiation of DNA in a fully aqueous environment}, series = {Physical chemistry, chemical physics : PCCP ; a journal of European chemical societies}, volume = {19}, journal = {Physical chemistry, chemical physics : PCCP ; a journal of European chemical societies}, number = {3}, publisher = {RSC Publ.}, address = {Cambridge}, issn = {1463-9076}, doi = {10.1039/c6cp07707b}, pages = {1798 -- 1805}, year = {2017}, abstract = {We report on a study in which plasmid DNA in water was irradiated with 30 keV electrons generated by a scanning electron microscope and passed through a 100 nm thick Si3N4 membrane. The corresponding Monte Carlo simulations suggest that the kinetic energy spectrum of the electrons throughout the water is dominated by low energy electrons (<100 eV). The DNA radiation damage, single-strand breaks (SSBs) and double-strand breaks (DSBs), was determined by gel electrophoresis. The median lethal dose of D-1/2 = 1.7 +/- 0.3 Gy was found to be much smaller as compared to partially or fully hydrated DNA irradiated under vacuum conditions. The ratio of the DSBs to SSBs was found to be 1 : 12 as compared to 1 : 88 found for hydrated DNA. Our method enables quantitative measurements of radiation damage to biomolecules (DNA, proteins) in solutions under varying conditions (pH, salinity, co-solutes) for an electron energy range which is difficult to probe by standard methods.}, language = {en} } @article{HaaseKrostSauteretal.2017, author = {Haase, Tobias and Krost, Annalena and Sauter, Tilman and Kratz, Karl and Peter, Jan and Kamann, Stefanie and Jung, Friedrich and Lendlein, Andreas and Zohlnh{\"o}fer, Dietlind and R{\"u}der, Constantin}, title = {In vivo biocompatibility assessment of poly (ether imide) electrospun scaffolds}, series = {Journal of Tissue Engineering and Regenerative Medicine}, volume = {11}, journal = {Journal of Tissue Engineering and Regenerative Medicine}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {1932-6254}, doi = {10.1002/term.2002}, pages = {1034 -- 1044}, year = {2017}, abstract = {Poly(ether imide) (PEI), which can be chemically functionalized with biologically active ligands, has emerged as a potential biomaterial for medical implants. Electrospun PEI scaffolds have shown advantageous properties, such as enhanced endothelial cell adherence, proliferation and low platelet adhesion in in vitro experiments. In this study, the in vivo behaviour of electrospun PEI scaffolds and PEI films was examined in a murine subcutaneous implantation model. Electrospun PEI scaffolds and films were surgically implanted subcutaneously in the dorsae of mice. The surrounding subcutaneous tissue response was examined via histopathological examination at 7 and 28days after implantation. No serious adverse events were observed for both types of PEI implants. The presence of macrophages or foreign body giant cells in the vicinity of the implants and the formation of a fibrous capsule indicated a normal foreign body reaction towards PEI films and scaffolds. Capsule thickness and inflammatory infiltration cells significantly decreased for PEI scaffolds during days 7-28 while remaining unchanged for PEI films. The infiltration of cells into the implant was observed for PEI scaffolds 7days after implantation and remained stable until 28days of implantation. Additionally some, but not all, PEI scaffold implants induced the formation of functional blood vessels in the vicinity of the implants. Conclusively, this study demonstrates the in vivo biocompatibility of PEI implants, with favourable properties of electrospun PEI scaffolds regarding tissue integration and wound healing.}, language = {en} } @phdthesis{Gorka2017, author = {G{\´o}rka, Michal Jakub}, title = {Establishing a pipeline for identification of protein- protein interactions using different native fractionation methods}, school = {Universit{\"a}t Potsdam}, pages = {109}, year = {2017}, language = {en} }