TY - JOUR A1 - Haase, Tobias A1 - Krost, Annalena A1 - Sauter, Tilman A1 - Kratz, Karl A1 - Peter, Jan A1 - Kamann, Stefanie A1 - Jung, Friedrich A1 - Lendlein, Andreas A1 - Zohlnhöfer, Dietlind A1 - Rüder, Constantin T1 - In vivo biocompatibility assessment of poly (ether imide) electrospun scaffolds JF - Journal of Tissue Engineering and Regenerative Medicine N2 - 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. KW - poly(ether imide) KW - in vivo study KW - electrospun scaffold KW - capsule formation KW - foreign body giant cells KW - vascularization Y1 - 2017 U6 - https://doi.org/10.1002/term.2002 SN - 1932-6254 SN - 1932-7005 VL - 11 IS - 4 SP - 1034 EP - 1044 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Hahn, Marc Benjamin A1 - Meyer, Susann A1 - Schröter, Maria-Astrid A1 - Seitz, Harald A1 - Kunte, Hans-Jörg A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Direct electron irradiation of DNA in a fully aqueous environment BT - Damage determination in combination with Monte Carlo simulations JF - Physical chemistry, chemical physics : PCCP ; a journal of European chemical societies N2 - 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. Y1 - 2016 U6 - https://doi.org/10.1039/c6cp07707b SN - 1463-9076 SN - 1463-9084 VL - 19 IS - 3 SP - 1798 EP - 1805 PB - RSC Publ. CY - Cambridge ER - TY - JOUR A1 - Hansen, Bjoern Oest A1 - Meyer, Etienne H. A1 - Ferrari, Camilla A1 - Vaid, Neha A1 - Movahedi, Sara A1 - Vandepoele, Klaas A1 - Nikoloski, Zoran A1 - Mutwil, Marek T1 - Ensemble gene function prediction database reveals genes important for complex I formation in Arabidopsis thaliana JF - New phytologist : international journal of plant science N2 - 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. KW - Arabidopsis thaliana KW - co-function network KW - complex I KW - ensemble prediction KW - gene function prediction Y1 - 2017 U6 - https://doi.org/10.1111/nph.14921 SN - 0028-646X SN - 1469-8137 VL - 217 IS - 4 SP - 1521 EP - 1534 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Hocher, Berthold T1 - Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy JF - Journal of Molecular Endocrinology N2 - 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. KW - DPP-4 KW - diabetic nephropathy KW - DPP-4 inhibitors KW - GLP-1 and SDF-1a Y1 - 2017 U6 - https://doi.org/10.1530/JME-17-0005 SN - 0952-5041 SN - 1479-6813 VL - 59 SP - R1 EP - R10 PB - Bioscientifica LTD CY - Bristol ER - TY - THES A1 - Heim, Olga T1 - Spatiotemporal effects on bat activity above intensively managed farmland N2 - Intakte und widerstandsfähige Ökosysteme sind essenziell für die Aufrechterhaltung optimaler Lebensbedingungen für das Leben auf der Erde. Die Basis für solche Ökosysteme bilden intakte ökologische Wechselwirkungen zwischen einer Vielzahl von Arten. Durch den beispiellosen Verlust der Biodiversität, welcher durch die in der zweiten Hälfte des 20. Jahrhunderts zunehmende Intensivierung der Agrarwirtschaft und die Zerstörung und Fragmentierung von Habitaten hervorgerufen wurde, können ökologische Wechselwirkungen und damit die Funktionsfähigkeit von Agrarökosystemen stark eingeschränkt werden. Um den Rückgang der Biodiversität in Agrarökosystemen abschwächen zu können, müssen wir die ökologischen Wechselwirkungen in Agrarökosystemen besser verstehen. Hierbei spielen Fledermäuse eine besondere Rolle, weil sie verschiedenste ökologische Nischen besetzen und eine Reihe von Ökosystemleistungen erfüllen so wie z.B. die Kontrolle von Schädlingspopulationen in Agrarlandschaften. Überdies trägt die Ordnung der Fledermäuse (Chiroptera) beträchtlich zur globalen Diversität der Säugetiere bei. Obwohl viele Fledermauspopulationen durch die Intensivierung der Agrarwirtschaft dezimiert wurden, ist noch relativ wenig darüber bekannt wie unterschiedliche Fledermausarten die offene Agrarlandschaft nutzen. Dieses Wissen ist jedoch essenziell für den Schutz von Fledermausarten in intensiv bewirtschafteten Agrarlandschaften und dringend notwendig besonders vor dem Hintergrund der vorhergesagten erweiterten Ausweitung der intensiven Agrarwirtschaft. Zusätzlich werden Fledermäuse durch den zuletzt massiven Ausbau von Windkraftanlagen, welche für viele Vogel- und Fledermausarten ein erhöhtes Tötungsrisiko darstellen, bedroht. Das Ziel dieser Dissertation war es deshalb, die Einflüsse ausgewählter raum-zeitlicher Faktoren auf die artspezifische Fledermausaktivität über intensiv genutzten Agrarflächen in einer von Agrarwirtschaft dominierten Landschaft zu untersuchen. Dazu habe ich die Fledermausaktivität mittels passiver akustischer Echoortungsaufnahme in den Jahren 2012 bis 2014 auf insgesamt 113 Untersuchungsflächen in offenen Ackerflächen im Nordosten Brandenburgs erfasst. Die Echoortungsrufe in etwa 27.779 Aufnahmen habe ich manuell bis auf die Art bestimmt und die berechneten artspezifischen Aktivitätsparameter mit Hilfe von komplexen statistischen Verfahren untersucht. Im ersten Kapitel dieser Arbeit, habe ich die berechneten Aktivitätsparameter von ökologisch unterschiedlichen Fledermausgruppen auf saisonale Muster hin untersucht. Dabei war ich besonders an Unterschieden zu den bekannten saisonalen Aktivitätsmustern in naturnahen Habitaten interessiert. Im zweiten Kapitel dieser Arbeit, habe ich den Einfluss von linearen Gehölzstrukturen am Feldrand und von kleinen Wasserflächen (Söllen) innerhalb von Ackerflächen auf die Flug- und Jagdaktivität verschiedener Fledermausarten über diesen Flächen untersucht. Zusätzlich war ich daran interessiert, ob sich etwaige Effekte dieser Landschaftselemente auf die Fledermausaktivität im Laufe des Jahres verändern. Im dritten Kapitel dieser Arbeit war es mein Ziel den Zusammenhang zwischen unterschiedlichen räumlichen und zeitlichen Einflüssen auf die artspezifische Fledermausaktivität über offenen Agrarflächen zu untersuchen. Dabei habe ich meine Untersuchungen auf Faktoren fokussiert, die dafür bekannt sind Fledermausaktivität zu beeinflussen, wie z.B. Faktoren auf kleinräumiger Skala, die mit der Beuteverfügbarkeit zusammenhängen, und verschiedene Landschaftscharakteristika auf großräumiger Skala. Auf der zeitlichen Skala, habe ich mich auf den Einfluss der Saison konzentriert. Zusammenfassend heben die Ergebnisse dieser Arbeit die Wichtigkeit naturnaher Landschaftselemente für die Fledermausaktivität über Agrarflächen hervor. Allerdings war nicht nur die Landschaftsstruktur für die Fledermausaktivität über Ackerflächen ausschlaggebend, sondern auch der Einfluss von interaktiven Effekten zwischen z.B. Landschaftscharakteristika und der lokalen Beuteverfügbarkeit. Ein weiteres Kernergebnis ist die saisonale Variabilität des Einflusses der Landschaftsstruktur auf die Fledermausaktivität. Hierbei hatten bestimmte Landschaftselemente vor allem im Sommer einen großen Einfluss auf die Fledermausaktivität. Das Potenzial der Ökosystemleistung durch spezifische Fledermausarten, welches wiederholt in den unterschiedlichen Kapiteln hervorgehoben wurde, ist ein weiteres Kernergebnis. Da die Fledermausaktivität jedoch stark von der Landschaftsstruktur in der Umgebung abhängt, ist es wichtig diese fledermausfreundlich zu gestalten, um die Ökosystemleistung der Schädlingskontrolle über Agrarflächen nutzen zu können. Schlussendlich trägt diese Arbeit in ihrer Gesamtheit zum bestehenden Wissen über die Fledermausbiologie und -ökologie bei und verdeutlicht die komplexen Wechselwirkungen unterschiedlicher Einflüsse auf mehreren raum-zeitlichen Ebenen. Die Ergebnisse dieser Arbeit können als Basis zur Verbesserung und Entwicklung von Schutzmaßnahmen für Fledermäuse in intensiv genutzten Agrarlandschaften dienen. Da Fledermäuse als gute Bioindikatoren gelten, können effektive Schutzmaßnahmen für Fledermäuse auch zum Schutz anderer Arten beitragen und damit potenziell den weiteren Verlust der Biodiversität in Agrarlandschaften abschwächen. N2 - Biodiversity and intact ecological interactions form the basis for functional and resilient ecosystems that maintain optimal conditions for life on earth. During the second half of the 20th century, especially land-use changes and an intensification of agricultural management caused an unprecedented loss of biodiversity in agroecosystems worldwide. Concerns have been raised that the ongoing loss of biodiversity would ultimately lead to impaired ecological interactions and ecosystem functioning in agricultural landscapes. In order to stop biodiversity loss while producing enough food for a growing world population, we need to gain detailed knowledge on ecological interactions and the functioning of agroecosystems as a whole. Bats (Chiroptera) represent an important component of global biodiversity, occupy a variety of ecological niches and fulfill numerous ecosystem services. Especially in temperate zone agroecosystems, bats were repeatedly reported to contribute to the reduction of pest insects above intensively managed arable fields. However, bat populations have been decimated by the consequence of land-use intensification which led to their legal protection status in the European Union (Council of Europe, 1979). The increasing number of wind turbines on arable fields poses an additional threat to bats as they might get injured or killed when flying too close to wind turbine blades. Although a large amount of land area is covered by arable fields, not much is known about how bats use the intensively managed agricultural landscape. In the present thesis, my general aim was to identify the relevance of factors at different spatiotemporal scales for shaping species-specific bat activity above intensively managed arable fields. Therefore, I repeatedly monitored bat activity above open arable fields in a landscape dominated by agriculture which is located in Northeast Brandenburg, Germany. From 2012 to 2014, I recorded echolocation calls of bats on a total of 113 sites using a passive acoustic approach. I obtained a total of 27,779 recordings, identified the recorded echolocation calls manually to species level and calculated species-specific bat activity measures. Depending on the focus of research, I modeled the obtained species-specific activity measures using generalized linear and additive mixed effect models. In Chapter I, I focused on identifying seasonal patterns in several species-specific activity measures of different functional bat groups. In Chapter II, I investigated small-scale effects of landscape elements, such as hedgerows and forest edges, on the flight and foraging activity of different bat species along the edge-field interface. Additionally, I aimed at identifying whether these effects are influenced by small ponds located within arable field and whether these effects change across seasons. In Chapter III, my aim was to investigate the interaction between factors from different spatiotemporal levels on the flight and foraging activity of bats above arable fields. At the small spatial scale, I focused on prey availability, at a large spatial scale on selected parameters which describe landscape characteristics and at the temporal scale on seasonal effects. The major findings obtained in each chapter can be summarized in the following three points. The first major finding is that not only landscape elements on a small spatial scale, e.g. a hedgerow at the edge of an arable field, but also landscape characteristics on a large spatial scale, e.g. landscape composition, shaped species-specific bat activity above open arable fields. This activity was also strongly influenced by interactions between landscape characteristics and local prey availability. Second, the influence of landscape elements and characteristics on bat activity above arable fields was not constant over time but changed across seasons with the strongest impact during summer as compared to spring and autumn. Third, I found indications of ecosystem service provided by N. noctula and P. nathusii in all three chapters, as especially these bat species were repeatedly found to forage above arable fields. This foraging activity was positively influenced by the proximity to landscape elements at the edge of the arable field but also by the presence of small ponds within the arable field. In light of the obtained findings, I strongly recommend protecting and most importantly recreating semi-natural landscape elements in the agricultural landscape. Furthermore, I strongly recommend against the construction of wind turbines close to these linear woody vegetation edges as bats were found to be active close to these landscape elements. Additionally, the operation times for wind turbines should be down-regulated during the mating and migration period in autumn due to high bat activity above arable fields. Since bats are considered being good bioindicators, effective conservation measures for bats might contribute to the protection of species from other taxa leading to an overall support of biodiversity in agricultural landscapes. In their entirety, the findings in this thesis contribute to the knowledge of different aspects of bat ecology and shed light on the complex interplay between factors from different spatiotemporal levels that shape bat activity above arable fields. Additionally, they can serve as a basis for the improvement and development of conservation measures for bats in agricultural landscapes. KW - European bats KW - Europäische Fledermausarten KW - conventional agriculture KW - konventionelle Landwirtschaft KW - landscape analysis KW - Landschaftsanalyse KW - conservation KW - Naturschutz Y1 - 2017 ER - TY - JOUR A1 - Heim, Olga A1 - Lenski, Johannes A1 - Schulze, Jelena A1 - Jung, Kirsten A1 - Kramer-Schadt, Stephanie A1 - Eccard, Jana A1 - Voigt, Christian C. T1 - The relevance of vegetation structures and small water bodies for bats foraging above farmland JF - Basic and applied ecology : Journal of the Gesellschaft für Ökologie N2 - 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. KW - Hedgerow KW - Forest edge KW - Pond KW - European bats KW - Agricultural landscape KW - Wind turbines Y1 - 2017 U6 - https://doi.org/10.1016/j.baae.2017.12.001 SN - 1439-1791 SN - 1618-0089 VL - 27 SP - 9 EP - 19 PB - Elsevier GMBH CY - München ER - TY - JOUR A1 - Heim, Wieland A1 - Trense, Daronja A1 - Sokolova, Galina V. A1 - Kitagawa, Tamaki T1 - Increased populations of endangered cranes after Amur River flood JF - Waterbirds N2 - 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. KW - Antigone vipio KW - cranes KW - dam construction KW - East Asian flyway KW - floodplain KW - Grus japonensis KW - Grus monacha KW - Leucogeranus leucogeranus KW - population trend KW - water level Y1 - 2017 U6 - https://doi.org/10.1675/063.040.0309 SN - 1524-4695 SN - 1938-5390 VL - 40 SP - 282 EP - 288 PB - Waterbirds SOC CY - Washington ER - TY - JOUR A1 - Heinze, Johannes A1 - Joshi, Jasmin Radha T1 - Plant-soil feedback effects can be masked by aboveground herbivory under natural field conditions JF - Oecologia N2 - 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. KW - Herbivores KW - Field experiment KW - Plant-community composition KW - Plant diversity KW - Plant-soil feedback Y1 - 2017 U6 - https://doi.org/10.1007/s00442-017-3997-y SN - 0029-8549 SN - 1432-1939 VL - 186 IS - 1 SP - 235 EP - 246 PB - Springer CY - New York ER - TY - JOUR A1 - Henkel, Janin A1 - Coleman, Charles Dominic A1 - Schraplau, Anne A1 - Jöhrens, Korinna A1 - Weber, Daniela A1 - Castro, Jose Pedro A1 - Hugo, Martin A1 - Schulz, Tim Julius A1 - Krämer, Stephanie A1 - Schürmann, Annette A1 - Püschel, Gerhard Paul T1 - Induction of Steatohepatitis (NASH) with Insulin Resistance in Wild-type B6 Mice by a Western-type Diet Containing Soybean Oil and Cholesterol JF - Molecular medicine N2 - 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. KW - Nonalcoholic Steatohepatitis (NASH) KW - Typical Western Diet KW - Nonalcoholic Fatty Liver Disease (NAFLD) KW - Dietary Cholesterol KW - Kupffer Cells Y1 - 2017 U6 - https://doi.org/10.2119/molmed.2016.00203 SN - 1076-1551 SN - 1528-3658 VL - 23 SP - 70 EP - 82 PB - Feinstein Inst. for Medical Research CY - Manhasset ER - TY - JOUR A1 - Heunisch, Fabian A1 - Chaykovska, Lyubov A1 - von Einem, Gina A1 - Alter, Markus A1 - Dschietzig, Thomas A1 - Kretschmer, Axel A1 - Kellner, Karl-Heinz A1 - Hocher, Berthold T1 - ADMA predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus undergoing coronary angiography JF - Medicine N2 - 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. KW - asymmetric dimethylarginine (ADMA) KW - biomarkers of renal failure KW - contrast-induced nephropathy Y1 - 2017 U6 - https://doi.org/10.1097/MD.0000000000006065 SN - 0025-7974 SN - 1536-5964 VL - 96 IS - 6 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Hoehn, Richard S. A1 - Jernigan, Peter L. A1 - Japtok, Lukasz A1 - Chang, Alex L. A1 - Midura, Emily F. A1 - Caldwell, Charles C. A1 - Kleuser, Burkhard A1 - Lentsch, Alex B. A1 - Edwards, Michael J. A1 - Gulbins, Erich A1 - Pritts, Timothy A. T1 - Acid sphingomyelinase inhibition in stored erythrocytes reduces transfusion-associated lung inflammation JF - Annals of surgery : a monthly review of surgical science and practice N2 - 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. KW - acid sphingomyelinase KW - blood banking KW - ceramide KW - lung inflammation KW - microparticle Y1 - 2017 U6 - https://doi.org/10.1097/SLA.0000000000001648 SN - 0003-4932 SN - 1528-1140 VL - 265 IS - 1 SP - 218 EP - 226 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Holzlöhner, Pamela A1 - Hanack, Katja T1 - Generation of murine monoclonal antibodies by hybridoma technology JF - JoVE : Video journal N2 - Monoclonal antibodies are universal binding molecules and are widely used in biomedicine and research. Nevertheless, the generation of these binding molecules is time-consuming and laborious due to the complicated handling and lack of alternatives. The aim of this protocol is to provide one standard method for the generation of monoclonal antibodies using hybridoma technology. This technology combines two steps. Step 1 is an appropriate immunization of the animal and step 2 is the fusion of B lymphocytes with immortal myeloma cells in order to generate hybrids possessing both parental functions, such as the production of antibody molecules and immortality. The generated hybridoma cells were then recloned and diluted to obtain stable monoclonal cell cultures secreting the desired monoclonal antibody in the culture supernatant. The supernatants were tested in enzyme-linked immunosorbent assays (ELISA) for antigen specificity. After the selection of appropriate cell clones, the cells were transferred to mass cultivation in order to produce the desired antibody molecule in large amounts. The purification of the antibodies is routinely performed by affinity chromatography. After purification, the antibody molecule can be characterized and validated for the final test application. The whole process takes 8 to 12 months of development, and there is a high risk that the antibody will not work in the desired test system. KW - Immunology KW - Issue 119 KW - monoclonal antibodies KW - hybridoma technology KW - myeloma cells KW - B lymphocytes KW - antigen KW - immunconjugate Y1 - 2017 U6 - https://doi.org/10.3791/54832 SN - 1940-087X IS - 119 PB - JoVE CY - Cambridge ER - TY - JOUR A1 - Hornick, Thomas A1 - Bach, Lennart T. A1 - Crawfurd, Katharine J. A1 - Spilling, Kristian A1 - Achterberg, Eric P. A1 - Woodhouse, Jason Nicholas A1 - Schulz, Kai G. A1 - Brussaard, Corina P. D. A1 - Riebesell, Ulf A1 - Grossart, Hans-Peter T1 - Ocean acidification impacts bacteria-phytoplankton coupling at low-nutrient conditions JF - Biogeosciences N2 - The oceans absorb about a quarter of the annually produced anthropogenic atmospheric carbon dioxide (CO2), resulting in a decrease in surface water pH, a process termed ocean acidification (OA). Surprisingly little is known about how OA affects the physiology of heterotrophic bacteria or the coupling of heterotrophic bacteria to phytoplankton when nutrients are limited. Previous experiments were, for the most part, undertaken during productive phases or following nutrient additions designed to stimulate algal blooms. Therefore, we performed an in situ large-volume mesocosm (similar to 55 m(3)) experiment in the Baltic Sea by simulating different fugacities of CO2 (fCO(2)) extending from present to future conditions. The study was conducted in July-August after the nominal spring bloom, in order to maintain low-nutrient conditions throughout the experiment. This resulted in phytoplankton communities dominated by small-sized functional groups (picophytoplankton). There was no consistent fCO(2)-induced effect on bacterial protein production (BPP), cell-specific BPP (csBPP) or biovolumes (BVs) of either free-living (FL) or particle-associated (PA) heterotrophic bacteria, when considered as individual components (univariate analyses). Permutational Multivariate Analysis of Variance (PERMANOVA) revealed a significant effect of the fCO(2) treatment on entire assemblages of dissolved and particulate nutrients, metabolic parameters and the bacteria-phytoplankton community. However, distance-based linear modelling only identified fCO(2) as a factor explaining the variability observed amongst the microbial community composition, but not for explaining variability within the metabolic parameters. This suggests that fCO(2) impacts on microbial metabolic parameters occurred indirectly through varying physicochemical parameters and microbial species composition. Cluster analyses examining the co-occurrence of different functional groups of bacteria and phytoplankton further revealed a separation of the four fCO(2)-treated mesocosms from both control mesocosms, indicating that complex trophic interactions might be altered in a future acidified ocean. Possible consequences for nutrient cycling and carbon export are still largely unknown, in particular in a nutrient-limited ocean. Y1 - 2017 U6 - https://doi.org/10.5194/bg-14-1-2017 SN - 1726-4170 SN - 1726-4189 VL - 14 IS - 1 SP - 1 EP - 15 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Ietswaart, Robert A1 - Rosa, Stefanie A1 - Wu, Zhe A1 - Dean, Caroline A1 - Howard, Martin T1 - Cell-Size-Dependent Transcription of FLC and Its Antisense Long Non-coding RNA COOLAIR Explain Cell-to-Cell Expression Variation JF - Cell systems N2 - Single-cell quantification of transcription kinetics and variability promotes a mechanistic understanding of gene regulation. Here, using single-molecule RNA fluorescence in situ hybridization and mathematical modeling, we dissect cellular RNA dynamics for Arabidopsis FLOWERING LOCUS C (FLC). FLC expression quantitatively determines flowering time and is regulated by antisense (COOLAIR) transcription. In cells without observable COOLAIR expression, we quantify FLC transcription initiation, elongation, intron processing, and lariat degradation, as well as mRNA release from the locus and degradation. In these heterogeneously sized cells, FLC mRNA number increases linearly with cell size, resulting in a large cell-to-cell variability in transcript level. This variation is accounted for by cell-sizedependent, Poissonian FLC mRNA production, but not by large transcriptional bursts. In COOLAIRexpressing cells, however, antisense transcription increases with cell size and contributes to FLC transcription decreasing with cell size. Our analysis therefore reveals an unexpected role for antisense transcription in modulating the scaling of transcription with cell size. Y1 - 2017 U6 - https://doi.org/10.1016/j.cels.2017.05.010 SN - 2405-4712 SN - 2405-4720 VL - 4 SP - 622 EP - 635 PB - Cell Press CY - Cambridge ER - TY - THES A1 - Janowski, Marcin Andrzej T1 - Investigating role of the essential GTPase - AtRsgA in the assembly of the small ribosomal subunit in Arabidopsis thaliana chloroplast Y1 - 2017 ER - TY - THES A1 - Janowski, Marcin Andrzej T1 - Investigating role of the essential GTPase - AtRsgA in the assembly of the small ribosomal subunit in Arabidopsis thaliana chloroplast N2 - Plastid protein biosynthesis occurs on bacterial-type 70S ribosomes consisting of a large (50S) and a small (30S) subunit. However, since many steps of ribosome biogenesis are not thermodynamically favorable at biological conditions, it requires many assembly factors. One group of assembly factors, circularly permuted GTPases, was implicated in 30S subunit maturation in E. coli, by a protein RsgA. RsgA orthologues are present in bacteria and plastid-containing species and in silico analysis revealed presence of a RsgA-like protein in Arabidopsis thaliana. To functionally characterize the Arabidopsis orthologue, two AtRsgA T-DNA insertion lines were analyzed in this study. The exon line (rsgA-e) led to embryo lethality, while the intron line (rsgA-i) caused severe dwarf, pale green phenotype. Further investigation of rsgA-i mutant line revealed defects in chloroplast biogenesis which led to increased number of chloroplasts, decreased chloroplast size, decreased air space between mesophyll cells and smaller shoot apical meristems, which showed unusual proplastid accumulation. Moreover, rsgA-i plants showed reduction in chlorophyll A and B content, decreased electron transport rate and photosynthetic efficiency. Further analyses revealed that the protein is involved in chloroplast 30S subunit maturation. Interestingly, we observed that while chloroplast-targeted and chloroplast-encoded proteins are generally downregulated in the mutant, a contrasting upregulation of the corresponding transcripts is observed, indicating an elaborate compensatory mechanism. To conclude, the study presented here reveals a ribosome assembly factor and a compensatory mechanism activated during impaired chloroplast function. KW - ribosome assembly KW - GTPase KW - chloro-ribosome KW - translation Y1 - 2017 ER - TY - JOUR A1 - Kang, Mi-Sun A1 - Lim, Hae-Soon A1 - Oh, Jong-Suk A1 - Lim, You-jin A1 - Wuertz-Kozak, Karin A1 - Harro, Janette M. A1 - Shirtliff, Mark E. A1 - Achermann, Yvonne T1 - Antimicrobial activity of Lactobacillus salivarius and Lactobacillus fermentum against Staphylococcus aureus JF - Pathogens and disease / Federation of European Microbiology Societies N2 - The increasing prevalence of methicillin-resistant Staphylococcus aureus has become a major public health threat. While lactobacilli were recently found useful in combating various pathogens, limited data exist on their therapeutic potential for S. aureus infections. The aim of this study was to determine whether Lactobacillus salivarius was able to produce bactericidal activities against S. aureus and to determine whether the inhibition was due to a generalized reduction in pH or due to secreted Lactobacillus product(s). We found an 8.6-log10 reduction of planktonic and a 6.3-log10 reduction of biofilm S. aureus. In contrast, the previously described anti-staphylococcal effects of L. fermentum only caused a 4.0-log10 reduction in planktonic S. aureus cells, with no effect on biofilm S. aureus cells. Killing of S. aureus was partially pH dependent, but independent of nutrient depletion. Cell-free supernatant that was pH neutralized and heat inactivated or proteinase K treated had significantly reduced killing of L. salivarius than with pH-neutralized supernatant alone. Proteomic analysis of the L. salivarius secretome identified a total of five secreted proteins including a LysM-containing peptidoglycan binding protein and a protein peptidase M23B. These proteins may represent potential novel anti-staphylococcal agents that could be effective against S. aureus biofilms. KW - antibacterial activity KW - biofilm KW - Lactobacillus fermentum KW - Lactobacillus salivarius KW - LysM KW - Staphylococcus aureus Y1 - 2017 U6 - https://doi.org/10.1093/femspd/ftx009 SN - 2049-632X VL - 75 IS - 2 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Kehlmaier, Christian A1 - Barlow, Axel A1 - Hastings, Alexander K. A1 - Vamberger, Melita A1 - Paijmans, Johanna L. A. A1 - Steadman, David W. A1 - Albury, Nancy A. A1 - Franz, Richard A1 - Hofreiter, Michael A1 - Fritz, Uwe T1 - Tropical ancient DNA reveals relationships of the extinct bahamian giant tortoise Chelonoidis alburyorum JF - Proceedings of the Royal Society of London : Series B, Biological sciences N2 - Ancient DNA of extinct species from the Pleistocene and Holocene has provided valuable evolutionary insights. However, these are largely restricted to mammals and high latitudes because DNA preservation in warm climates is typically poor. In the tropics and subtropics, non-avian reptiles constitute a significant part of the fauna and little is known about the genetics of the many extinct reptiles from tropical islands. We have reconstructed the near-complete mitochondrial genome of an extinct giant tortoise from the Bahamas (Chelonoidis alburyorum) using an approximately 1000-year-old humerus from a water-filled sinkhole (blue hole) on Great Abaco Island. Phylogenetic and molecular clock analyses place this extinct species as closely related to Galapagos (C. niger complex) and Chaco tortoises (C. chilensis), and provide evidence for repeated overseas dispersal in this tortoise group. The ancestors of extant Chelonoidis species arrived in South America from Africa only after the opening of the Atlantic Ocean and dispersed from there to the Caribbean and the Galapagos Islands. Our results also suggest that the anoxic, thermally buffered environment of blue holes may enhance DNA preservation, and thus are opening a window for better understanding evolution and population history of extinct tropical species, which would likely still exist without human impact. KW - Bahamas KW - biogeography KW - extinction KW - palaeontology KW - phylogeny Y1 - 2017 U6 - https://doi.org/10.1098/rspb.2016.2235 SN - 0962-8452 SN - 1471-2954 VL - 284 PB - The Royal Society CY - London ER - TY - THES A1 - Kersting, Sebastian T1 - Isothermal nucleic acid amplification for the detection of infectious pathogens Y1 - 2017 ER - TY - GEN A1 - Kleine-Vehn, Jürgen A1 - Sauer, Michael ED - Kleine-Vehn, Jürgen ED - Sauer, Michael T1 - Preface T2 - Plant Hormones: Methods and Protocols Y1 - 2017 SN - 978-1-4939-6469-7 SN - 978-1-4939-6467-3 U6 - https://doi.org/10.1007/978-1-4939-6469-7 SN - 1064-3745 SN - 1940-6029 VL - 1497 SP - V EP - V PB - Springer CY - New York ET - 3 ER -