@article{BerryRosaHowardetal.2017, author = {Berry, Scott and Rosa, Stefanie and Howard, Martin and Buhler, Marc and Dean, Caroline}, title = {Disruption of an RNA-binding hinge region abolishes LHP1-mediated epigenetic repression}, series = {Genes \& Development}, volume = {31}, journal = {Genes \& Development}, publisher = {Cold Spring Harbor Laboratory Press}, address = {Cold Spring Harbor, NY}, issn = {0890-9369}, doi = {10.1101/gad.305227.117}, pages = {2115 -- 2120}, year = {2017}, abstract = {Epigenetic maintenance of gene repression is essential for development. Polycomb complexes are central to this memory, but many aspects of the underlying mechanism remain unclear. LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) binds Polycomb-deposited H3K27me3 and is required for repression of many Polycomb target genes in Arabidopsis. Here we show that LHP1 binds RNA in vitro through the intrinsically disordered hinge region. By independently perturbing the RNA-binding hinge region and H3K27me3 (trimethylation of histone H3 at Lys27) recognition, we found that both facilitate LHP1 localization and H3K27me3 maintenance. Disruption of the RNAbinding hinge region also prevented formation of subnuclear foci, structures potentially important for epigenetic repression.}, language = {en} } @article{EndesfelderWeicheltStraussetal.2017, author = {Endesfelder, Stefanie and Weichelt, Ulrike and Strauß, Evelyn and Schl{\"o}r, Anja and Sifringer, Marco and Scheuer, Till and B{\"u}hrer, Christoph and Schmitz, Thomas}, title = {Neuroprotection by caffeine in hyperoxia-induced neonatal brain injury}, series = {International journal of molecular sciences}, volume = {18}, journal = {International journal of molecular sciences}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms18010187}, pages = {24}, year = {2017}, abstract = {Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28-32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80\% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.}, language = {en} } @article{WeithoffTaubeBolius2017, author = {Weithoff, Guntram and Taube, Anne and Bolius, Sarah}, title = {The invasion success of the cyanobacterium Cylindrospermopsis raciborskii in experimental mesocosms}, series = {Aquatic Invasions}, volume = {12}, journal = {Aquatic Invasions}, publisher = {Regional Euro-Asian Biological Invasions centre-reabic}, address = {Helsinki}, issn = {1798-6540}, doi = {10.3391/ai.2017.12.3.07}, pages = {333 -- 341}, year = {2017}, abstract = {The potentially toxic, invasive cyanobacterium Cylindrospermopsis raciborskii, originating from sub-tropical regions, has spread into temperate climate zones in almost all continents. Potential factors in its success are temperature, light and nutrient levels. Grazing losses through zooplankton have been measured in the laboratory but are typically not regarded as a factor in (failed) invasion success. In some potentially suitable lakes, C. raciborskii has never been found, although it is present in water bodies close by. Therefore, we tested the invasive potential of three different isolates introduced into natural plankton communities using laboratory mesocosm experiments under three grazing levels: ambient zooplankton densities, removal of large species using 100 mu m mesh and a ca. doubling of large species. Three C. raciborskii isolates originating from the same geographic region (North-East Germany) were added separately to the four replicates of each treatment and kept in semi-continuous cultures for 21 days. Two isolates disappeared from the mesocosms and were also not viable in filtered lake water indicating that the lake water itself or the switch from culture medium to lake water led to the decay of the inoculated C. raciborskii. Only one out of the three isolates persisted in the plankton communities at a rather low level and only in the treatment without larger zooplankton. This result demonstrates that under potentially suitable environmental conditions, top-down control from zooplankton might hamper the establishment of C. raciborskii. Non-metric multidimensional scaling showed distinct variation in resident phytoplankton communities between the different grazing levels, thus differential grazing impact shaped the resident community in different ways allowing C. raciborskii only to invade under competitive (= low grazing pressure) conditions. Furthermore, even after invasion failure, the temporary presence of C. raciborskii influenced the phytoplankton community.}, language = {en} } @misc{YarmanJetzschmannNeumannetal.2017, author = {Yarman, Aysu and Jetzschmann, Katharina J. and Neumann, Bettina and Zhang, Xiaorong and Wollenberger, Ulla and Cordin, Aude and Haupt, Karsten and Scheller, Frieder W.}, title = {Enzymes as Tools in MIP-Sensors}, series = {Chemosensors}, volume = {5}, journal = {Chemosensors}, publisher = {MDPI}, address = {Basel}, issn = {2227-9040}, doi = {10.3390/chemosensors5020011}, pages = {16}, year = {2017}, abstract = {Molecularly imprinted polymers (MIPs) have the potential to complement antibodies in bioanalysis, are more stable under harsh conditions, and are potentially cheaper to produce. However, the affinity and especially the selectivity of MIPs are in general lower than those of their biological pendants. Enzymes are useful tools for the preparation of MIPs for both low and high-molecular weight targets: As a green alternative to the well-established methods of chemical polymerization, enzyme-initiated polymerization has been introduced and the removal of protein templates by proteases has been successfully applied. Furthermore, MIPs have been coupled with enzymes in order to enhance the analytical performance of biomimetic sensors: Enzymes have been used in MIP-sensors as tracers for the generation and amplification of the measuring signal. In addition, enzymatic pretreatment of an analyte can extend the analyte spectrum and eliminate interferences.}, language = {en} } @article{ThomasCarvalhoHaileetal.2017, author = {Thomas, Jessica E. and Carvalho, Gary R. and Haile, James and Martin, Michael D. and Castruita, Jose A. Samaniego and Niemann, Jonas and Sinding, Mikkel-Holger S. and Sandoval-Velasco, Marcela and Rawlence, Nicolas J. and Fuller, Errol and Fjeldsa, Jon and Hofreiter, Michael and Stewart, John R. and Gilbert, M. Thomas P. and Knapp, Michael}, title = {An ‛Aukward' tale}, series = {Genes}, volume = {8}, journal = {Genes}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2073-4425}, doi = {10.3390/genes8060164}, pages = {164}, year = {2017}, abstract = {One hundred and seventy-three years ago, the last two Great Auks, Pinguinus impennis, ever reliably seen were killed. Their internal organs can be found in the collections of the Natural History Museum of Denmark, but the location of their skins has remained a mystery. In 1999, Great Auk expert Errol Fuller proposed a list of five potential candidate skins in museums around the world. Here we take a palaeogenomic approach to test which—if any—of Fuller's candidate skins likely belong to either of the two birds. Using mitochondrial genomes from the five candidate birds (housed in museums in Bremen, Brussels, Kiel, Los Angeles, and Oldenburg) and the organs of the last two known individuals, we partially solve the mystery that has been on Great Auk scholars' minds for generations and make new suggestions as to the whereabouts of the still-missing skin from these two birds.}, language = {en} } @article{GisderSchuelerHorchleretal.2017, author = {Gisder, Sebastian and Sch{\"u}ler, Vivian and Horchler, Lennart L. and Groth, Detlef and Genersch, Elke}, title = {Long-Term Temporal Trends of Nosema spp. Infection Prevalence in Northeast Germany}, series = {Frontiers in cellular and infection microbiology}, volume = {7}, journal = {Frontiers in cellular and infection microbiology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {2235-2988}, doi = {10.3389/fcimb.2017.00301}, pages = {14}, year = {2017}, abstract = {The Western honey bee (Apis mellifera) is widely used as commercial pollinator in worldwide agriculture and, therefore, plays an important role in global food security. Among the parasites and pathogens threatening health and survival of honey bees are two species of microsporidia, Nosema apis and Nosema ceranae. Nosema ceranae is considered an emerging pathogen of the Western honey bee. Reports on the spread of N. ceranae suggested that this presumably highly virulent species is replacing its more benign congener N. apis in the global A. mellifera population. We here present a 12 year longitudinal cohort study on the prevalence of N. apis and N. ceranae in Northeast Germany. Between 2005 and 2016, a cohort of about 230 honey bee colonies originating from 23 apiaries was sampled twice a year (spring and autumn) resulting in a total of 5,600 bee samples which were subjected to microscopic and molecular analysis for determining the presence of infections with N. apis or/and N. ceranae. Throughout the entire study period, both N. apis- and N. ceranae-infections could be diagnosed within the cohort. Logistic regression analysis of the prevalence data demonstrated a significant increase of N. ceranae-infections over the last 12 years, both in autumn (reflecting the development during the summer) and in spring (reflecting the development over winter) samples. Cell culture experiments confirmed that N. ceranae has a higher proliferative potential than N. apis at 27. and 33 degrees C potentially explaining the increase in N. ceranae prevalence during summer. In autumn, characterized by generally low infection prevalence, this increase was accompanied by a significant decrease in N. apis- infection prevalence. In contrast, in spring, the season with a higher prevalence of infection, no significant decrease of N. apis infections despite a significant increase in N. ceranae infections could be observed. Therefore, our data do not support a general advantage of N. ceranae over N. apis and an overall replacement of N. apis by N. ceranae in the studied honey bee population.}, language = {en} } @article{ParagasHumphreysMinetal.2017, author = {Paragas, Erickson M. and Humphreys, Sara C. and Min, Joshua and Joswig-Jones, Carolyn A. and Leimk{\"u}hler, Silke and Jones, Jeffrey P.}, title = {ecoAO}, series = {ACS OMEGA}, volume = {2}, journal = {ACS OMEGA}, publisher = {American Chemical Society}, address = {Washington}, issn = {2470-1343}, doi = {10.1021/acsomega.7b01054}, pages = {4820 -- 4827}, year = {2017}, abstract = {Although aldehyde oxidase (AO) is an important hepatic drug-metabolizing enzyme, it remains understudied and is consequently often overlooked in preclinical studies, an oversight that has resulted in the failure of multiple clinical trials. AO's preclusion to investigation stems from the following: (1) difficulties synthesizing metabolic standards due to the chemospecificity and regiospecificity of the enzyme and (2) significant inherent variability across existing in vitro systems including liver cytosol, S9 fractions, and primary hepatocytes, which lack specificity and generate discordant expression and activity profiles. Here, we describe a practical bacterial biotransformation system, ecoAO, addressing both issues simultaneously. ecoAO is a cell paste of MoCo-producing Escherichia coli strain TP1017 expressing human AO. It exhibits specific activity toward known substrates, zoniporide, 4-trans-(N,N-dimethylamino)cinnamaldehyde, O6-benzylguanine, and zaleplon; it also has utility as a biocatalyst, yielding milligram quantities of synthetically challenging metabolite standards such as 2-oxo-zoniporide. Moreover, ecoAO enables routine determination of kcat and V/K, which are essential parameters for accurate in vivo clearance predictions. Furthermore, ecoAO has potential as a preclinical in vitro screening tool for AO activity, as demonstrated by its metabolism of 3-aminoquinoline, a previously uncharacterized substrate. ecoAO promises to provide easy access to metabolites with the potential to improve pharmacokinetic clearance predictions and guide drug development.}, language = {en} } @article{BuschKlausPenoneetal.2017, author = {Busch, Verena and Klaus, Valentin H. and Penone, Caterina and Sch{\"a}fer, Deborah and Boch, Steffen and Prati, Daniel and M{\"u}ller, J{\"o}rg and Socher, Stephanie A. and Niinemets, {\"U}lo and Penuelas, Josep and H{\"o}lzel, Norbert and Fischer, Markus and Kleinebecker, Till}, title = {Nutrient stoichiometry and land use rather than species richness determine plant functional diversity}, series = {Ecology and evolution}, volume = {8}, journal = {Ecology and evolution}, number = {1}, publisher = {Wiley}, address = {Hoboken}, issn = {2045-7758}, doi = {10.1002/ece3.3609}, pages = {601 -- 616}, year = {2017}, abstract = {Plant functional traits reflect individual and community ecological strategies. They allow the detection of directional changes in community dynamics and ecosystemic processes, being an additional tool to assess biodiversity than species richness. Analysis of functional patterns in plant communities provides mechanistic insight into biodiversity alterations due to anthropogenic activity. Although studies have consi-dered of either anthropogenic management or nutrient availability on functional traits in temperate grasslands, studies combining effects of both drivers are scarce. Here, we assessed the impacts of management intensity (fertilization, mowing, grazing), nutrient stoichiometry (C, N, P, K), and vegetation composition on community-weighted means (CWMs) and functional diversity (Rao's Q) from seven plant traits in 150 grasslands in three regions in Germany, using data of 6 years. Land use and nutrient stoichiometry accounted for larger proportions of model variance of CWM and Rao's Q than species richness and productivity. Grazing affected all analyzed trait groups; fertilization and mowing only impacted generative traits. Grazing was clearly associated with nutrient retention strategies, that is, investing in durable structures and production of fewer, less variable seed. Phenological variability was increased. Fertilization and mowing decreased seed number/mass variability, indicating competition-related effects. Impacts of nutrient stoichiometry on trait syndromes varied. Nutrient limitation (large N:P, C:N ratios) promoted species with conservative strategies, that is, investment in durable plant structures rather than fast growth, fewer seed, and delayed flowering onset. In contrast to seed mass, leaf-economics variability was reduced under P shortage. Species diversity was positively associated with the variability of generative traits. Synthesis. Here, land use, nutrient availability, species richness, and plant functional strategies have been shown to interact complexly, driving community composition, and vegetation responses to management intensity. We suggest that deeper understanding of underlying mechanisms shaping community assembly and biodiversity will require analyzing all these parameters.}, language = {en} } @article{LaemkeBaeurle2017, author = {L{\"a}mke, J{\"o}rn and B{\"a}urle, Isabel}, title = {Epigenetic and chromatin-based mechanisms in environmental stress adaptation and stress memory in plants}, series = {Genome biology : biology for the post-genomic era}, volume = {18}, journal = {Genome biology : biology for the post-genomic era}, publisher = {BioMed Central}, address = {London}, issn = {1474-760X}, doi = {10.1186/s13059-017-1263-6}, pages = {8685 -- 8693}, year = {2017}, abstract = {Plants frequently have to weather both biotic and abiotic stressors, and have evolved sophisticated adaptation and defense mechanisms. In recent years, chromatin modifications, nucleosome positioning, and DNA methylation have been recognized as important components in these adaptations. Given their potential epigenetic nature, such modifications may provide a mechanistic basis for a stress memory, enabling plants to respond more efficiently to recurring stress or even to prepare their offspring for potential future assaults. In this review, we discuss both the involvement of chromatin in stress responses and the current evidence on somatic, intergenerational, and transgenerational stress memory.}, language = {en} } @article{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 = {Biomimetics}, volume = {2}, journal = {Biomimetics}, number = {4}, publisher = {MDPI}, address = {Basel}, issn = {2313-7673}, doi = {10.3390/biomimetics2040024}, pages = {21}, 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} } @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{ZimmermannRaschkeEppetal.2017, author = {Zimmermann, Heike Hildegard and Raschke, Elena and Epp, Laura Saskia and Stoof-Leichsenring, Kathleen Rosemarie and Schirrmeister, Lutz and Schwamborn, Georg and Herzschuh, Ulrike}, title = {The history of tree and shrub taxa on Bol'shoy Lyakhovsky Island (New Siberian Archipelago) since the Last Interglacial Uncovered by Sedimentary Ancient DNA and Pollen Data}, series = {Genes}, volume = {8}, journal = {Genes}, number = {10}, publisher = {MDPI}, address = {Basel}, issn = {2073-4425}, doi = {10.3390/genes8100273}, pages = {273}, year = {2017}, abstract = {Ecosystem boundaries, such as the Arctic-Boreal treeline, are strongly coupled with climate and were spatially highly dynamic during past glacial-interglacial cycles. Only a few studies cover vegetation changes since the last interglacial, as most of the former landscapes are inundated and difficult to access. Using pollen analysis and sedimentary ancient DNA (sedaDNA) metabarcoding, we reveal vegetation changes on Bol'shoy Lyakhovsky Island since the last interglacial from permafrost sediments. Last interglacial samples depict high levels of floral diversity with the presence of trees (Larix, Picea, Populus) and shrubs (Alnus, Betula, Ribes, Cornus, Saliceae) on the currently treeless island. After the Last Glacial Maximum, Larix re-colonised the island but disappeared along with most shrub taxa. This was probably caused by Holocene sea-level rise, which led to increased oceanic conditions on the island. Additionally, we applied two newly developed larch-specific chloroplast markers to evaluate their potential for tracking past population dynamics from environmental samples. The novel markers were successfully re-sequenced and exhibited two variants of each marker in last interglacial samples. SedaDNA can track vegetation changes as well as genetic changes across geographic space through time and can improve our understanding of past processes that shape modern patterns.}, language = {en} } @article{WurzbacherFuchsAttermeyeretal.2017, author = {Wurzbacher, Christian and Fuchs, Andrea and Attermeyer, Katrin and Frindte, Katharina and Grossart, Hans-Peter and Hupfer, Michael and Casper, Peter and Monaghan, Michael T.}, title = {Shifts among Eukaryota, Bacteria, and Archaea define the vertical organization of a lake sediment}, series = {Microbiome}, volume = {5}, journal = {Microbiome}, publisher = {BioMed Central}, address = {London}, issn = {2049-2618}, doi = {10.1186/s40168-017-0255-9}, pages = {16}, year = {2017}, abstract = {Background: Lake sediments harbor diverse microbial communities that cycle carbon and nutrients while being constantly colonized and potentially buried by organic matter sinking from the water column. The interaction of activity and burial remained largely unexplored in aquatic sediments. We aimed to relate taxonomic composition to sediment biogeochemical parameters, test whether community turnover with depth resulted from taxonomic replacement or from richness effects, and to provide a basic model for the vertical community structure in sediments. Methods: We analyzed four replicate sediment cores taken from 30-m depth in oligo-mesotrophic Lake Stechlin in northern Germany. Each 30-cm core spanned ca. 170 years of sediment accumulation according to Cs-137 dating and was sectioned into layers 1-4 cm thick. We examined a full suite of biogeochemical parameters and used DNA metabarcoding to examine community composition of microbial Archaea, Bacteria, and Eukaryota. Results: Community beta-diversity indicated nearly complete turnover within the uppermost 30 cm. We observed a pronounced shift from Eukaryota- and Bacteria-dominated upper layers (<5 cm) to Bacteria-dominated intermediate layers (5-14 cm) and to deep layers (>14 cm) dominated by enigmatic Archaea that typically occur in deep-sea sediments. Taxonomic replacement was the prevalent mechanism in structuring the community composition and was linked to parameters indicative of microbial activity (e.g., CO2 and CH4 concentration, bacterial protein production). Richness loss played a lesser role but was linked to conservative parameters (e.g., C, N, P) indicative of past conditions. Conclusions: By including all three domains, we were able to directly link the exponential decay of eukaryotes with the active sediment microbial community. The dominance of Archaea in deeper layers confirms earlier findings from marine systems and establishes freshwater sediments as a potential low-energy environment, similar to deep sea sediments. We propose a general model of sediment structure and function based on microbial characteristics and burial processes. An upper "replacement horizon" is dominated by rapid taxonomic turnover with depth, high microbial activity, and biotic interactions. A lower "depauperate horizon" is characterized by low taxonomic richness, more stable "low-energy" conditions, and a dominance of enigmatic Archaea.}, language = {en} } @article{EhmannZollerMinichmayretal.2017, author = {Ehmann, Lisa and Zoller, Michael and Minichmayr, Iris K. and Scharf, Christina and Maier, Barbara and Schmitt, Maximilian V. and Hartung, Niklas and Huisinga, Wilhelm and Vogeser, Michael and Frey, Lorenz and Zander, Johannes and Kloft, Charlotte}, title = {Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients}, series = {Critical care}, volume = {21}, journal = {Critical care}, publisher = {BioMed Central}, address = {London}, issn = {1466-609X}, doi = {10.1186/s13054-017-1829-4}, pages = {14}, year = {2017}, abstract = {Background: Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. Methods: A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCRCG). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100\% T->MIC, 50\% T->4xMIC) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCRCG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Results: Large inter-and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100\% T->MIC was merely 48.4\% and 20.6\%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50\% T->4xMIC. A hyperbolic relationship between CLCRCG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C-8h) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment). Conclusions: The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy-and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed.}, language = {en} } @misc{ReilRosenfeldImholtetal.2017, author = {Reil, Daniela and Rosenfeld, Ulrike and Imholt, Christian and Schmidt, Sabrina and Ulrich, Rainer G. and Eccard, Jana and Jacob, Jens}, title = {Puumala hantavirus infections in bank vole populations}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {957}, issn = {1866-8372}, doi = {10.25932/publishup-43123}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431232}, pages = {15}, year = {2017}, abstract = {Background In Europe, bank voles (Myodes glareolus) are widely distributed and can transmit Puumala virus (PUUV) to humans, which causes a mild to moderate form of haemorrhagic fever with renal syndrome, called nephropathia epidemica. Uncovering the link between host and virus dynamics can help to prevent human PUUV infections in the future. Bank voles were live trapped three times a year in 2010-2013 in three woodland plots in each of four regions in Germany. Bank vole population density was estimated and blood samples collected to detect PUUV specific antibodies. Results We demonstrated that fluctuation of PUUV seroprevalence is dependent not only on multi-annual but also on seasonal dynamics of rodent host abundance. Moreover, PUUV infection might affect host fitness, because seropositive individuals survived better from spring to summer than uninfected bank voles. Individual space use was independent of PUUV infections. Conclusions Our study provides robust estimations of relevant patterns and processes of the dynamics of PUUV and its rodent host in Central Europe, which are highly important for the future development of predictive models for human hantavirus infection risk.}, language = {en} } @article{ReilRosenfeldImholtetal.2017, author = {Reil, Daniela and Rosenfeld, Ulrike and Imholt, Christian and Schmidt, Sabrina and Ulrich, Rainer G. and Eccard, Jana and Jacob, Jens}, title = {Puumala hantavirus infections in bank vole populations}, series = {BMC ecology}, volume = {17}, journal = {BMC ecology}, publisher = {BioMed Central}, address = {London}, issn = {1472-6785}, doi = {10.1186/s12898-017-0118-z}, pages = {13}, year = {2017}, abstract = {Background In Europe, bank voles (Myodes glareolus) are widely distributed and can transmit Puumala virus (PUUV) to humans, which causes a mild to moderate form of haemorrhagic fever with renal syndrome, called nephropathia epidemica. Uncovering the link between host and virus dynamics can help to prevent human PUUV infections in the future. Bank voles were live trapped three times a year in 2010-2013 in three woodland plots in each of four regions in Germany. Bank vole population density was estimated and blood samples collected to detect PUUV specific antibodies. Results We demonstrated that fluctuation of PUUV seroprevalence is dependent not only on multi-annual but also on seasonal dynamics of rodent host abundance. Moreover, PUUV infection might affect host fitness, because seropositive individuals survived better from spring to summer than uninfected bank voles. Individual space use was independent of PUUV infections. Conclusions Our study provides robust estimations of relevant patterns and processes of the dynamics of PUUV and its rodent host in Central Europe, which are highly important for the future development of predictive models for human hantavirus infection risk}, language = {en} }