@article{RodriguesNagowskiMusseletal.2018, author = {Rodrigues, Johannes and Nagowski, Natalie and Mussel, Patrick and Hewig, Johannes}, title = {Altruistic punishment is connected to trait anger, not trait altruism, if compensation is available}, series = {Heliyon}, volume = {4}, journal = {Heliyon}, number = {11}, doi = {10.1016/j.heliyon.2018.e00962}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177669}, pages = {e00962}, year = {2018}, abstract = {Altruistic punishment and altruistic compensation are important concepts that are used to investigate altruism. However, altruistic punishment has been found to be correlated with anger. We were interested whether altruistic punishment and altruistic compensation are both driven by trait altruism and trait anger or whether the influence of those two traits is more specific to one of the behavioral options. We found that if the participants were able to apply altruistic compensation and altruistic punishment together in one paradigm, trait anger only predicts altruistic punishment and trait altruism only predicts altruistic compensation. Interestingly, these relations are disguised in classical altruistic punishment and altruistic compensation paradigms where participants can either only punish or compensate. Hence altruistic punishment and altruistic compensation paradigms should be merged together if one is interested in trait altruism without the confounding influence of trait anger.}, language = {en} } @article{PfisterSchwarz2018, author = {Pfister, Roland and Schwarz, Katharina A.}, title = {Should we pre-date the beginning of scientific psychology to 1787?}, series = {Frontiers in Psychology}, volume = {9}, journal = {Frontiers in Psychology}, number = {2481}, doi = {10.3389/fpsyg.2018.02481}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177641}, year = {2018}, abstract = {No abstract available.}, language = {en} } @article{KellerBrandelBeckeretal.2018, author = {Keller, Alexander and Brandel, Annette and Becker, Mira C. and Balles, Rebecca and Abdelmohsen, Usama Ramadan and Ankenbrand, Markus J. and Sickel, Wiebke}, title = {Wild bees and their nests host Paenibacillus bacteria with functional potential of avail}, series = {Microbiome}, volume = {6}, journal = {Microbiome}, number = {229}, doi = {10.1186/s40168-018-0614-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177554}, year = {2018}, abstract = {Background: In previous studies, the gram-positive firmicute genus Paenibacillus was found with significant abundances in nests of wild solitary bees. Paenibacillus larvae is well-known for beekeepers as a severe pathogen causing the fatal honey bee disease American foulbrood, and other members of the genus are either secondary invaders of European foulbrood or considered a threat to honey bees. We thus investigated whether Paenibacillus is a common bacterium associated with various wild bees and hence poses a latent threat to honey bees visiting the same flowers. Results: We collected 202 samples from 82 individuals or nests of 13 bee species at the same location and screened each for Paenibacillus using high-throughput sequencing-based 16S metabarcoding. We then isolated the identified strain Paenibacillus MBD-MB06 from a solitary bee nest and sequenced its genome. We did find conserved toxin genes and such encoding for chitin-binding proteins, yet none specifically related to foulbrood virulence or chitinases. Phylogenomic analysis revealed a closer relationship to strains of root-associated Paenibacillus rather than strains causing foulbrood or other accompanying diseases. We found anti-microbial evidence within the genome, confirmed by experimental bioassays with strong growth inhibition of selected fungi as well as gram-positive and gram-negative bacteria. Conclusions: The isolated wild bee associate Paenibacillus MBD-MB06 is a common, but irregularly occurring part of wild bee microbiomes, present on adult body surfaces and guts and within nests especially in megachilids. It was phylogenetically and functionally distinct from harmful members causing honey bee colony diseases, although it shared few conserved proteins putatively toxic to insects that might indicate ancestral predisposition for the evolution of insect pathogens within the group. By contrast, our strain showed anti-microbial capabilities and the genome further indicates abilities for chitin-binding and biofilm-forming, suggesting it is likely a useful associate to avoid fungal penetration of the bee cuticula and a beneficial inhabitant of nests to repress fungal threats in humid and nutrient-rich environments of wild bee nests.}, language = {en} } @article{FeldheimKesslerSchmittetal.2018, author = {Feldheim, Jonas and Kessler, Almuth F and Schmitt, Dominik and Wilczek, Lara and Linsenmann, Thomas and Dahlmann, Mathias and Monoranu, Camelia M and Ernestus, Ralf-Ingo and Hagemann, Carsten and L{\"o}hr, Mario}, title = {Expression of activating transcription factor 5 (ATF5) is increased in astrocytomas of different WHO grades and correlates with survival of glioblastoma patients}, series = {OncoTargets and Therapy}, volume = {11}, journal = {OncoTargets and Therapy}, doi = {10.2147/OTT.S176549}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177541}, pages = {8673-8684}, year = {2018}, abstract = {Background: ATF5 suppresses differentiation of neuroprogenitor cells and is overexpressed in glioblastoma (GBM). A reduction of its expression leads to apoptotic GBM cell death. Data on ATF5 expression in astrocytoma WHO grade II (low-grade astrocytoma [LGA]) are scarce and lacking on recurrent GBM. Patients and methods: ATF5 mRNA was extracted from frozen samples of patients' GBM (n=79), LGA (n=40), and normal brain (NB, n=10), quantified by duplex qPCR and correlated with retrospectively collected clinical data. ATF5 protein expression was evaluated by measuring staining intensity on immunohistochemistry. Results: ATF5 mRNA was overexpressed in LGA (sevenfold, P<0.001) and GBM (tenfold, P<0.001) compared to NB, which was confirmed on protein level. Although ATF5 mRNA expression in GBM showed a considerable fluctuation range, groups of varying biological behavior, that is, local/multifocal growth or primary tumor/relapse and the tumor localization at diagnosis, were not significantly different. ATF5 mRNA correlated with the patients' age (r=0.339, P=0.028) and inversely with Ki67-staining (r=-0.421, P=0.007). GBM patients were allocated to a low and a high ATF5 expression group by the median ATF5 overexpression compared to NB. Kaplan-Meier analysis and Cox regression indicated that ATF5 mRNA expression significantly correlated with short-term survival (t<12 months, median survival 18 vs 13 months, P=0.022, HR 2.827) and progression-free survival (PFS) (12 vs 6 months, P=0.024). This advantage vanished after 24 months (P=0.084). Conclusion: ATF5 mRNA expression could be identified as an additional, though not independent factor correlating with overall survival and PFS. Since its inhibition might lead to the selective death of glioma cells, it might serve as a potential ubiquitous therapeutic target in astrocytic tumors.}, language = {en} } @article{RuedenauerWoehrleSpaetheetal.2018, author = {Ruedenauer, Fabian A. and W{\"o}hrle, Christine and Spaethe, Johannes and Leonhardt, Sara D.}, title = {Do honeybees (Apis mellifera) differentiate between different pollen types?}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0205821}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177537}, pages = {e0205821}, year = {2018}, abstract = {Bees receive nectar and pollen as reward for pollinating plants. Pollen of different plant species varies widely in nutritional composition. In order to select pollen of appropriate nutritional quality, bees would benefit if they could distinguish different pollen types. Whether they rely on visual, olfactory and/or chemotactile cues to distinguish between different pollen types, has however been little studied. In this study, we examined whether and how Apis mellifera workers differentiate between almond and apple pollen. We used differential proboscis extension response conditioning with olfactory and chemotactile stimulation, in light and darkness, and in summer and winter bees. We found that honeybees were only able to differentiate between different pollen types, when they could use both chemotactile and olfactory cues. Visual cues further improved learning performance. Summer bees learned faster than winter bees. Our results thus highlight the importance of multisensory information for pollen discrimination.}, language = {en} } @article{BeckYuStrzelczykPaulsetal.2018, author = {Beck, Sebastian and Yu-Strzelczyk, Jing and Pauls, Dennis and Constantin, Oana M. and Gee, Christine E. and Ehmann, Nadine and Kittel, Robert J. and Nagel, Georg and Gao, Shiqiang}, title = {Synthetic light-activated ion channels for optogenetic activation and inhibition}, series = {Frontiers in Neuroscience}, volume = {12}, journal = {Frontiers in Neuroscience}, number = {643}, doi = {10.3389/fnins.2018.00643}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177520}, year = {2018}, abstract = {Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2\(^{2+}\)) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca\(^{2+}\) might be desirable. Moreover, there is need for an efficient light-gated potassium (K\(^{+}\)) channel that can rapidly inhibit spiking in targeted neurons. Considering the importance of Ca\(^{2+}\) and K\(^{+}\) in cell physiology, light-activated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels would be welcome additions to the optogenetic toolbox. Here we describe the engineering of novel light-gated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high permeability for Ca\(^{2+}\) or for K\(^{+}\), respectively. Optimized fusion constructs showed strong light-gated conductance in Xenopus laevis oocytes and in rat hippocampal neurons. These constructs could also be used to control the motility of Drosophila melanogaster larvae, when expressed in motoneurons. Illumination led to body contraction when motoneurons expressed the light-sensitive Ca\(^{2+}\)-permeant channel, and to body extension when expressing the light-sensitive K\(^{+}\) channel, both effectively and reversibly paralyzing the larvae. Further optimization of these constructs will be required for application in adult flies since both constructs led to eclosion failure when expressed in motoneurons.}, language = {en} } @article{TianGaovonderHeydeetal.2018, author = {Tian, Yuehui and Gao, Shiqiang and von der Heyde, Eva Laura and Hallmann, Armin and Nagel, Georg}, title = {Two-component cyclase opsins of green algae are ATP-dependent and light-inhibited guanylyl cyclases}, series = {BMC Biology}, volume = {16}, journal = {BMC Biology}, number = {144}, doi = {10.1186/s12915-018-0613-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177516}, year = {2018}, abstract = {Background: The green algae Chlamydomonas reinhardtii and Volvox carteri are important models for studying light perception and response, expressing many different photoreceptors. More than 10 opsins were reported in C. reinhardtii, yet only two—the channelrhodopsins—were functionally characterized. Characterization of new opsins would help to understand the green algae photobiology and to develop new tools for optogenetics. Results: Here we report the characterization of a novel opsin family from these green algae: light-inhibited guanylyl cyclases regulated through a two-component-like phosphoryl transfer, called "two-component cyclase opsins" (2c-Cyclops). We prove the existence of such opsins in C. reinhardtii and V. carteri and show that they have cytosolic N- and C-termini, implying an eight-transmembrane helix structure. We also demonstrate that cGMP production is both light-inhibited and ATP-dependent. The cyclase activity of Cr2c-Cyclop1 is kept functional by the ongoing phosphorylation and phosphoryl transfer from the histidine kinase to the response regulator in the dark, proven by mutagenesis. Absorption of a photon inhibits the cyclase activity, most likely by inhibiting the phosphoryl transfer. Overexpression of Vc2c-Cyclop1 protein in V. carteri leads to significantly increased cGMP levels, demonstrating guanylyl cyclase activity of Vc2c-Cyclop1 in vivo. Live cell imaging of YFP-tagged Vc2c-Cyclop1 in V. carteri revealed a development-dependent, layer-like structure at the immediate periphery of the nucleus and intense spots in the cell periphery. Conclusions: Cr2c-Cyclop1 and Vc2c-Cyclop1 are light-inhibited and ATP-dependent guanylyl cyclases with an unusual eight-transmembrane helix structure of the type I opsin domain which we propose to classify as type Ib, in contrast to the 7 TM type Ia opsins. Overexpression of Vc2c-Cyclop1 protein in V. carteri led to a significant increase of cGMP, demonstrating enzyme functionality in the organism of origin. Fluorescent live cell imaging revealed that Vc2c-Cyclop1 is located in the periphery of the nucleus and in confined areas at the cell periphery.}, language = {en} } @article{StrohmeierWalterRotheetal.2018, author = {Strohmeier, Michael and Walter, Thomas and Rothe, Julian and Montenegro, Sergio}, title = {Ultra-wideband based pose estimation for small unmanned aerial vehicles}, series = {IEEE Access}, volume = {6}, journal = {IEEE Access}, doi = {10.1109/ACCESS.2018.2873571}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177503}, pages = {57526-57535}, year = {2018}, abstract = {This paper proposes a 3-D local pose estimation system for a small Unmanned Aerial Vehicle (UAV) with a weight limit of 200 g and a very small footprint of 10 cm×10cm. The system is realized by fusing 3-D position estimations from an Ultra-Wide Band (UWB) transceiver network with Inertial Measurement Unit (IMU) sensor data and data from a barometric pressure sensor. The 3-D position from the UWB network is estimated using Multi-Dimensional Scaling (MDS) and range measurements between the transceivers. The range measurements are obtained using Double-Sided Two-Way Ranging (DS-TWR), thus eliminating the need for an additional clock synchronization mechanism. The sensor fusion is accomplished using a loosely coupled Extended Kalman Filter (EKF) architecture. Extensive evaluation of the proposed system shows that a position accuracy with a Root-Mean-Square Error (RMSE) of 0.20cm can be obtained. The orientation angle can be estimated with an RMSE of 1.93°.}, language = {en} } @article{LotzKiesewetterSchmidetal.2018, author = {Lotz, C. and Kiesewetter, L. and Schmid, F. F. and Hansmann, J. and Walles, H. and Groeber-Becker, F.}, title = {Replacing the Draize eye test: impedance spectroscopy as a 3R method to discriminate between all GHS categories for eye irritation}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {15049}, doi = {10.1038/s41598-018-33118-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177492}, year = {2018}, abstract = {Highly invasive animal based test procedures for risk assessment such as the Draize eye test are under increasing criticism due to poor transferability for the human organism and animal-welfare concerns. However, besides all efforts, the Draize eye test is still not completely replaced by alternative animal-free methods. To develop an in vitro test to identify all categories of eye irritation, we combined organotypic cornea models based on primary human cells with an electrical readout system that measures the impedance of the test models. First, we showed that employing a primary human cornea epithelial cell based model is advantageous in native marker expression to the primary human epidermal keratinocytes derived models. Secondly, by employing a non-destructive measuring system based on impedance spectroscopy, we could increase the sensitivity of the test system. Thereby, all globally harmonized systems categories of eye irritation could be identified by repeated measurements over a period of 7 days. Based on a novel prediction model we achieved an accuracy of 78\% with a reproducibility of 88.9\% to determine all three categories of eye irritation in one single test. This could pave the way according to the 3R principle to replace the Draize eye test.}, language = {en} } @article{HaringSelvinHeetal.2018, author = {Haring, Bernhard and Selvin, Elizabeth and He, Xintong and Coresh, Josef and Steffen, Lyn M. and Folsom, Aaron R. and Tang, Weihong and Rebholz, Casey M.}, title = {Adherence to the dietary approaches to stop hypertension dietary pattern and risk of abdominal aortic aneurysm: results from the ARIC study}, series = {Journal of the American Heart Association}, volume = {7}, journal = {Journal of the American Heart Association}, number = {21}, doi = {10.1161/JAHA.118.009340}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177442}, pages = {e009340}, year = {2018}, abstract = {Background The role of a healthy dietary pattern in the prevention of abdominal aortic aneurysms (AAA) is unknown. We aimed to evaluate the relationship between adherence to a Dietary Approaches To Stop Hypertension-style dietary pattern and the risk of incident AAAs. Methods and Results Dietary intake was assessed via a 66-item food frequency questionnaire at baseline (1987-1989) and at visit 3 (1993-1995) in 13 496 participants enrolled in the ARIC (Atherosclerosis Risk in Communities) study without clinical AAA (mean age, 54 years). A dietary scoring index based on food times was constructed to assess self-reported adherence to a dietary approaches to stop hypertension-style dietary pattern. Participants were followed for incident clinical AAAs using hospital discharge diagnoses, Medicare inpatient and outpatient diagnoses, or death certificates through December 31, 2011. Cox proportional hazards models with covariate adjustment were used to estimate hazard ratios with 95\% confidence intervals. During a median follow-up of 23 years, there were 517 incident AAA cases. Individuals with a Dietary Approaches To Stop Hypertension-style diet score in the highest quintile had a 40\% lower risk of hospitalization for AAA than those in the lowest quintile (hazard ratio\(_{Q5}\) vs \(_{Q1}\): 0.60; 95\% confidence intervals: 0.44, 0.83; P\(_{trend}\)=0.002). In detailed analyses, higher consumption of fruits, vegetables, whole grains, low-fat dairy, and nuts and legumes was related to a lower risk for AAA. Conclusions Greater adherence to a Dietary Approaches To Stop Hypertension-style dietary pattern was associated with lower risk for AAA. Higher consumption of fruits, vegetables, whole grains, low-fat dairy as well as nuts and legumes may help to decrease the burden of AAAs.}, language = {en} } @article{BoelchRuecklFuchsetal.2018, author = {Boelch, Sebastian P. and Rueckl, Kilian and Fuchs, Clara and Jordan, Martin and Knauer, Markus and Steinert, Andre and Rudert, Maximilian and Luedemann, Martin}, title = {Comparison of elution characteristics and compressive strength of biantibiotic-loaded PMMA bone cement for spacers: Copal\(^®\) spacem with gentamicin and vancomycin versus Palacos\(^®\) R+G with vancomycin}, series = {BioMed Research International}, volume = {2018}, journal = {BioMed Research International}, number = {4323518}, doi = {10.1155/2018/4323518}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177435}, year = {2018}, abstract = {Purpose. Copal\(^®\) spacem is a new PMMA bone cement for fabricating spacers. This study compares elution of gentamicin, elution of vancomycin, and compressive strength of Copal\(^®\) spacem and of Palacos\(^®\) R+G at different vancomycin loadings in the powder of the cements. We hypothesized that antibiotic elution of Copal\(^®\) spacem is superior at comparable compressive strength. Methods. Compression test specimens were fabricated using Copal\(^®\) spacem manually loaded with 0.5 g gentamicin and additionally 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (COP specimens) and using 0.5 g gentamicin premixed Palacos\(^®\) R+G manually loaded with 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (PAL specimens). These specimens were used for determination of gentamicin and vancomycin elution (in fetal calf serum, at 22°C) and for determination of compressive strength both prior and following the elution tests. Results. Cumulative gentamicin concentrations (p < 0.005) and gentamicin concentration after 28 days (p ≤ 0.043) were significantly lower for COP specimens compared to PAL specimens. Cumulative vancomycin concentrations were significantly higher (p ≤ 0.043) for COP specimens after the second day. Vancomycin concentrations after 28 days were not significantly higher for the Copal specimens loaded with 2 g and 4 g of vancomycin. Compressive strength was not significantly different between COP specimens and PAL specimens before elution tests. Compressive strength after the elution tests was significantly lower (p = 0.005) for COP specimens loaded with 2 g of vancomycin. Conclusion. We could not demonstrate consistent superior antibiotic elution from Copal\(^®\) spacem compared to Palacos\(^®\) R+G for fabricating gentamicin and vancomycin loaded spacers. The results do not favor Copal\(^®\) spacem over Palacos\(^®\) R+G for the use as a gentamicin and vancomycin biantibiotic-loaded spacer.}, language = {en} } @article{PaulsBlechschmidtFrantzmannetal.2018, author = {Pauls, Dennis and Blechschmidt, Christine and Frantzmann, Felix and el Jundi, Basil and Selcho, Mareike}, title = {A comprehensive anatomical map of the peripheral octopaminergic/tyraminergic system of Drosophila melanogaster}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {15314}, doi = {10.1038/s41598-018-33686-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177412}, year = {2018}, abstract = {The modulation of an animal's behavior through external sensory stimuli, previous experience and its internal state is crucial to survive in a constantly changing environment. In most insects, octopamine (OA) and its precursor tyramine (TA) modulate a variety of physiological processes and behaviors by shifting the organism from a relaxed or dormant condition to a responsive, excited and alerted state. Even though OA/TA neurons of the central brain are described on single cell level in Drosophila melanogaster, the periphery was largely omitted from anatomical studies. Given that OA/TA is involved in behaviors like feeding, flying and locomotion, which highly depend on a variety of peripheral organs, it is necessary to study the peripheral connections of these neurons to get a complete picture of the OA/TA circuitry. We here describe the anatomy of this aminergic system in relation to peripheral tissues of the entire fly. OA/TA neurons arborize onto skeletal muscles all over the body and innervate reproductive organs, the heart, the corpora allata, and sensory organs in the antennae, legs, wings and halteres underlining their relevance in modulating complex behaviors.}, language = {en} } @article{RufWirbelauerBeissertetal.2018, author = {Ruf, Katharina and Wirbelauer, Johannes and Beissert, Antje and Frieauff, Eric}, title = {Successful treatment of severe arterial hypotension and anuria in a preterm infant with renal tubular dysgenesis- a case report}, series = {Maternal Health, Neonatology and Perinatology}, volume = {4}, journal = {Maternal Health, Neonatology and Perinatology}, number = {27}, doi = {10.1186/s40748-018-0095-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177405}, year = {2018}, abstract = {Background: Oligohydramnios sequence can be caused by renal tubular dysgenesis (RTD), a rare condition resulting in pulmonary and renal morbidity. Besides typical features of Potter-sequence, the infants present with severe arterial hypotension and anuria as main symptoms. Establishing an adequate arterial blood pressure and sufficient renal perfusion is crucial for the survival of these infants. Case presentation: We describe a male preterm infant of 34 + 0 weeks of gestation. Prenatally oligohydramnios of unknown cause was detected. After uneventful delivery and good adaptation the infant developed respiratory distress due to a spontaneous right-sided pneumothorax and required thoracocentesis and placement of a chest tube; he showed no major respiratory concerns thereafter and needed only minimal ventilatory support. Echocardiography revealed no abnormalities, especially no pulmonary hypertension. However, he suffered from severe arterial hypotension and anuria refractory to catecholamine therapy (dobutamine, epinephrine and noradrenaline). After 36 h of life, vasopressin therapy was initiated resulting in an almost immediate stabilization of arterial blood pressure and subsequent onset of diuresis. Therapy with vasopressin was necessary for three weeks to maintain adequate arterial blood pressure levels and diuresis. Sepsis and adrenal insufficiency were ruled out as inflammation markers, microbiological tests and cortisol level were normal. At two weeks of age, our patient developed electrolyte disturbances which were successfully treated with fludrocortisone. He did not need renal replacement therapy. Genetic analyses revealed a novel compound hyterozygous mutation of RTD. Now 17 months of age, the patient is in clinically stable condition with treatment of fludrocortisone and sodium bicarbonate. He suffers from stage 2 chronic kidney disease; blood pressure, motor and cognitive development are normal. Conclusions: RTD is a rare cause of oligohydramnios sequence. Next to pulmonary hypoplasia, severe arterial hypotension is responsible for poor survival. We present the only second surviving infant with RTD, who did not require renal replacement therapy during the neonatal period. It can be speculated whether the use of vasopressin prevents renal replacement therapy as vasopressin increases urinary output by improving renal blood flow.}, language = {en} } @article{BakhtiarizadehHosseinpourShahhoseinietal.2018, author = {Bakhtiarizadeh, Mohammad Reza and Hosseinpour, Batool and Shahhoseini, Maryam and Korte, Arthur and Gifani, Peyman}, title = {Weighted gene co-expression network analysis of endometriosis and identification of functional modules associated with its main hallmarks}, series = {Frontiers in Genetics}, volume = {9}, journal = {Frontiers in Genetics}, number = {453}, doi = {10.3389/fgene.2018.00453}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177376}, year = {2018}, abstract = {Although many genes have been identified using high throughput technologies in endometriosis (ES), only a small number of individual genes have been analyzed functionally. This is due to the complexity of the disease that has different stages and is affected by various genetic and environmental factors. Many genes are upregulated or downregulated at each stage of the disease, thus making it difficult to identify key genes. In addition, little is known about the differences between the different stages of the disease. We assumed that the study of the identified genes in ES at a system-level can help to better understand the molecular mechanism of the disease at different stages of the development. We used publicly available microarray data containing archived endometrial samples from women with minimal/mild endometriosis (MMES), mild/severe endometriosis (MSES) and without endometriosis. Using weighted gene co-expression analysis (WGCNA), functional modules were derived from normal endometrium (NEM) as the reference sample. Subsequently, we tested whether the topology or connectivity pattern of the modules was preserved in MMES and/or MSES. Common and specific hub genes were identified in non-preserved modules. Accordingly, hub genes were detected in the non-preserved modules at each stage. We identified sixteen co-expression modules. Of the 16 modules, nine were non-preserved in both MMES and MSES whereas five were preserved in NEM, MMES, and MSES. Importantly, two non-preserved modules were found in either MMES or MSES, highlighting differences between the two stages of the disease. Analyzing the hub genes in the non-preserved modules showed that they mostly lost or gained their centrality in NEM after developing the disease into MMES and MSES. The same scenario was observed, when the severeness of the disease switched from MMES to MSES. Interestingly, the expression analysis of the new selected gene candidates including CC2D2A, AEBP1, HOXB6, IER3, and STX18 as well as IGF-1, CYP11A1 and MMP-2 could validate such shifts between different stages. The overrepresented gene ontology (GO) terms were enriched in specific modules, such as genetic disposition, estrogen dependence, progesterone resistance and inflammation, which are known as endometriosis hallmarks. Some modules uncovered novel co-expressed gene clusters that were not previously discovered.}, language = {en} } @article{WeigelSchmitzPfisteretal.2018, author = {Weigel, Tobias and Schmitz, Tobias and Pfister, Tobias and Gaetzner, Sabine and Jannasch, Maren and Al-Hijailan, Reem and Sch{\"u}rlein, Sebastian and Suliman, Salwa and Mustafa, Kamal and Hansmann, Jan}, title = {A three-dimensional hybrid pacemaker electrode seamlessly integrates into engineered, functional human cardiac tissue in vitro}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {14545}, doi = {10.1038/s41598-018-32790-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177368}, year = {2018}, abstract = {Pacemaker systems are an essential tool for the treatment of cardiovascular diseases. However, the immune system's natural response to a foreign body results in the encapsulation of a pacemaker electrode and an impaired energy efficiency by increasing the excitation threshold. The integration of the electrode into the tissue is affected by implant properties such as size, mechanical flexibility, shape, and dimensionality. Three-dimensional, tissue-like electrode scaffolds render an alternative to currently used planar metal electrodes. Based on a modified electrospinning process and a high temperature treatment, a conductive, porous fiber scaffold was fabricated. The electrical and immunological properties of this 3D electrode were compared to 2D TiN electrodes. An increased surface of the fiber electrode compared to the planar 2D electrode, showed an enhanced electrical performance. Moreover, the migration of cells into the 3D construct was observed and a lower inflammatory response was induced. After early and late in vivo host response evaluation subcutaneously, the 3D fiber scaffold showed no adverse foreign body response. By embedding the 3D fiber scaffold in human cardiomyocytes, a tissue-electrode hybrid was generated that facilitates a high regenerative capacity and a low risk of fibrosis. This hybrid was implanted onto a spontaneously beating, tissue-engineered human cardiac patch to investigate if a seamless electronic-tissue interface is generated. The fusion of this hybrid electrode with a cardiac patch resulted in a mechanical stable and electrical excitable unit. Thereby, the feasibility of a seamless tissue-electrode interface was proven.}, language = {en} } @article{SchliermannNickel2018, author = {Schliermann, Anna and Nickel, Joachim}, title = {Unraveling the connection between fibroblast growth factor and bone morphogenetic protein signaling}, series = {International Journal of Molecular Sciences}, volume = {19}, journal = {International Journal of Molecular Sciences}, number = {10}, issn = {1422-0067}, doi = {10.3390/ijms19103220}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177358}, year = {2018}, abstract = {Ontogeny of higher organisms as well the regulation of tissue homeostasis in adult individuals requires a fine-balanced interplay of regulating factors that individually trigger the fate of particular cells to either stay undifferentiated or to differentiate towards distinct tissue specific lineages. In some cases, these factors act synergistically to promote certain cellular responses, whereas in other tissues the same factors antagonize each other. However, the molecular basis of this obvious dual signaling activity is still only poorly understood. Bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs) are two major signal protein families that have a lot in common: They are both highly preserved between different species, involved in essential cellular functions, and their ligands vastly outnumber their receptors, making extensive signal regulation necessary. In this review we discuss where and how BMP and FGF signaling cross paths. The compiled data reflect that both factors synchronously act in many tissues, and that antagonism and synergism both exist in a context-dependent manner. Therefore, by challenging a generalization of the connection between these two pathways a new chapter in BMP FGF signaling research will be introduced.}, language = {en} } @article{MalschLimanWiedmannetal.2018, author = {Malsch, Carolin and Liman, Thomas and Wiedmann, Silke and Siegerink, Bob and Georgakis, Marios K. and Tiedt, Steffen and Endres, Matthias and Heuschmann, Peter U.}, title = {Outcome after stroke attributable to baseline factors—the PROSpective Cohort with Incident Stroke (PROSCIS)}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0204285}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177342}, pages = {e0204285}, year = {2018}, abstract = {Background The impact of risk factors on poor outcome after ischemic stroke is well known, but estimating the amount of poor outcome attributable to single factors is challenging in presence of multimorbidity. We aim to compare population attributable risk estimates obtained from different statistical approaches regarding their consistency. We use a real-life data set from the PROSCIS study to identify predictors for mortality and functional impairment one year after first-ever ischemic stroke and quantify their contribution to poor outcome using population attributable risks. Methods The PROSpective Cohort with Incident Stroke (PROSCIS) is a prospective observational hospital-based cohort study of patients after first-ever stroke conducted independently in Berlin (PROSCIS-B) and Munich (PROSCIS-M). The association of baseline factors with poor outcome one year after stroke in PROSCIS-B was analysed using multiple logistic regression analysis and population attributable risks were calculated, which were estimated using sequential population attributable risk based on a multiple generalized additive regression model, doubly robust estimation, as well as using average sequential population attributable risk. Findings were reproduced in an independent validation sample from PROSCIS-M. Results Out of 507 patients with available outcome information after 12 months in PROSCIS-B, 20.5\% suffered from poor outcome. Factors associated with poor outcome were age, pre-stroke physical disability, stroke severity (NIHSS), education, and diabetes mellitus. The order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but population attributable risk estimates varied markedly between the methods. In PROSCIS-M, incidence of poor outcome and distribution of baseline parameters were comparable. The multiple logistic regression model could be reproduced for all predictors, except pre-stroke physical disability. Similar to PROSCIS-B, the order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but magnitudes of population attributable risk differed markedly between the methods. Conclusions Ranking of risk factors by population impact is not affected by the different statistical approaches. Thus, for a rational decision on which risk factor to target in disease interventions, population attributable risk is a supportive tool. However, population attributable risk estimates are difficult to interpret and are not comparable when they origin from studies applying different methodology. The predictors for poor outcome identified in PROSCIS-B have a relevant impact on mortality and functional impairment one year after first-ever ischemic stroke.}, language = {en} } @article{JarickBertscheStahletal.2018, author = {Jarick, Marcel and Bertsche, Ute and Stahl, Mark and Schultz, Daniel and Methling, Karen and Lalk, Michael and Stigloher, Christian and Steger, Mirco and Schlosser, Andreas and Ohlsen, Knut}, title = {The serine/threonine kinase Stk and the phosphatase Stp regulate cell wall synthesis in Staphylococcus aureus}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {13693}, doi = {10.1038/s41598-018-32109-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177333}, year = {2018}, abstract = {The cell wall synthesis pathway producing peptidoglycan is a highly coordinated and tightly regulated process. Although the major components of bacterial cell walls have been known for decades, the complex regulatory network controlling peptidoglycan synthesis and many details of the cell division machinery are not well understood. The eukaryotic-like serine/threonine kinase Stk and the cognate phosphatase Stp play an important role in cell wall biosynthesis and drug resistance in S. aureus. We show that stp deletion has a pronounced impact on cell wall synthesis. Deletion of stp leads to a thicker cell wall and decreases susceptibility to lysostaphin. Stationary phase Δstp cells accumulate peptidoglycan precursors and incorporate higher amounts of incomplete muropeptides with non-glycine, monoglycine and monoalanine interpeptide bridges into the cell wall. In line with this cell wall phenotype, we demonstrate that the lipid II:glycine glycyltransferase FemX can be phosphorylated by the Ser/Thr kinase Stk in vitro. Mass spectrometric analyses identify Thr32, Thr36 and Ser415 as phosphoacceptors. The cognate phosphatase Stp dephosphorylates these phosphorylation sites. Moreover, Stk interacts with FemA and FemB, but is unable to phosphorylate them. Our data indicate that Stk and Stp modulate cell wall synthesis and cell division at several levels.}, language = {en} } @article{SperlichDeClerckZinneretal.2018, author = {Sperlich, Billy and De Clerck, Ine and Zinner, Christoph and Holmberg,, Hans-Christer and Wallmann-Sperlich, Birgit}, title = {Prolonged sitting interrupted by 6-min of high-intensity exercise: circulatory, metabolic, hormonal, thermal, cognitive, and perceptual responses}, series = {Frontiers in Physiology}, volume = {9}, journal = {Frontiers in Physiology}, number = {1279}, doi = {10.3389/fphys.2018.01279}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177307}, year = {2018}, abstract = {The aim was to examine certain aspects of circulatory, metabolic, hormonal, thermoregulatory, cognitive, and perceptual responses while sitting following a brief session of high-intensity interval exercise. Twelve students (five men; age, 22 ± 2 years) performed two trials involving either simply sitting for 180 min (SIT) or sitting for this same period with a 6-min session of high-intensity exercise after 60 min (SIT+HIIT). At T\(_0\) (after 30 min of resting), T\(_1\) (after a 20-min breakfast), T\(_2\) (after sitting for 1 h), T\(_3\) (immediately after the HIIT), T\(_4\), T\(_5\), T\(_6\), and T\(_7\) (30, 60, 90, and 120 min after the HIIT), circulatory, metabolic, hormonal, thermoregulatory, cognitive, and perceptual responses were assessed. The blood lactate concentration (at T\(_3\)-T\(_5\)), heart rate (at T\(_3\)-T\(_6\)), oxygen uptake (at T\(_3\)-T\(_7\)), respiratory exchange ratio, and sensations of heat (T\(_3\)-T\(_5\)), sweating (T\(_3\), T\(_4\)) and odor (T\(_3\)), as well as perception of vigor (T\(_3\)-T\(_6\)), were higher and the respiratory exchange ratio (T\(_4\)-T\(_7\)) and mean body and skin temperatures (T\(_3\)) lower in the SIT+HIIT than the SIT trial. Levels of blood glucose and salivary cortisol, cerebral oxygenation, and feelings of anxiety/depression, fatigue or hostility, as well as the variables of cognitive function assessed by the Stroop test did not differ between SIT and SIT+HIIT. In conclusion, interruption of prolonged sitting with a 6-min session of HIIT induced more pronounced circulatory and metabolic responses and improved certain aspects of perception, without affecting selected hormonal, thermoregulatory or cognitive functions.}, language = {en} } @article{KrishnaPeter2018, author = {Krishna, Anand and Peter, Sebastian M.}, title = {Questionable research practices in student final theses - prevalence, attitudes, and the role of the supervisor's perceived attitudes}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0203470}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177296}, pages = {e0203470}, year = {2018}, abstract = {Although questionable research practices (QRPs) and p-hacking have received attention in recent years, little research has focused on their prevalence and acceptance in students. Students are the researchers of the future and will represent the field in the future. Therefore, they should not be learning to use and accept QRPs, which would reduce their ability to produce and evaluate meaningful research. 207 psychology students and fresh graduates provided self-report data on the prevalence and predictors of QRPs. Attitudes towards QRPs, belief that significant results constitute better science or lead to better grades, motivation, and stress levels were predictors. Furthermore, we assessed perceived supervisor attitudes towards QRPs as an important predictive factor. The results were in line with estimates of QRP prevalence from academia. The best predictor of QRP use was students' QRP attitudes. Perceived supervisor attitudes exerted both a direct and indirect effect via student attitudes. Motivation to write a good thesis was a protective factor, whereas stress had no effect. Students in this sample did not subscribe to beliefs that significant results were better for science or their grades. Such beliefs further did not impact QRP attitudes or use in this sample. Finally, students engaged in more QRPs pertaining to reporting and analysis than those pertaining to study design. We conclude that supervisors have an important function in shaping students' attitudes towards QRPs and can improve their research practices by motivating them well. Furthermore, this research provides some impetus towards identifying predictors of QRP use in academia.}, language = {en} } @article{GrimmHufnagelWobseretal.2018, author = {Grimm, Johannes and Hufnagel, Anita and Wobser, Marion and Borst, Andreas and Haferkamp, Sebastian and Houben, Roland and Meierjohann, Svenja}, title = {BRAF inhibition causes resilience of melanoma cell lines by inducing the secretion of FGF1}, series = {Oncogenesis}, volume = {7}, journal = {Oncogenesis}, number = {71}, doi = {10.1038/s41389-018-0082-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177261}, year = {2018}, abstract = {Approximately half of all melanoma patients harbour activating mutations in the serine/threonine kinase BRAF. This is the basis for one of the main treatment strategies for this tumor type, the targeted therapy with BRAF and MEK inhibitors. While the initial responsiveness to these drugs is high, resistance develops after several months, frequently at sites of the previously responding tumor. This indicates that tumor response is incomplete and that a certain tumor fraction survives even in drug-sensitive patients, e.g., in a therapy-induced senescence-like state. Here, we show in several melanoma cell lines that BRAF inhibition induces a secretome with stimulating effect on fibroblasts and naive melanoma cells. Several senescence-associated factors were found to be transcribed and secreted in response to BRAF or MEK inhibition, among them members of the fibroblast growth factor family. We identified the growth factor FGF1 as mediator of resilience towards BRAF inhibition, which limits the pro-apoptotic effects of the drug and activates fibroblasts to secrete HGF. FGF1 regulation was mediated by the PI3K pathway and by FRA1, a direct target gene of the MAPK pathway. When FGFR inhibitors were applied in parallel to BRAF inhibitors, resilience was broken, thus providing a rationale for combined therapeutical application.}, language = {en} } @article{AbdelhafezFawzyFahimetal.2018, author = {Abdelhafez, Omnia Hesham and Fawzy, Michael Atef and Fahim, John Refaat and Desoukey, Samar Yehia and Krischke, Markus and Mueller, Martin J. and Abdelmohsen, Usama Ramadan}, title = {Hepatoprotective potential of Malvaviscus arboreus against carbon tetrachloride-induced liver injury in rats}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0202362}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177243}, pages = {e0202362}, year = {2018}, abstract = {Malvaviscus arboreus Cav. is a medicinal plant belonging to family Malvaceae with both ethnomedical and culinary value; however, its phytochemical and biological profiles have been scarcely studied. Accordingly, this work was designed to explore the chemical composition and the hepatoprotective potential of M. arboreus against carbon tetrachloride (CCl\(_4\))-induced hepatotoxicity. The total extract of the aerial parts and its derived fractions (petroleum ether, dichloromethane, ethyl acetate, and aqueous) were orally administered to rats for six consecutive days, followed by injection of CCl\(_4\) (1:1 v/v, in olive oil, 1.5 ml/kg, i.p.) on the next day. Results showed that the ethyl acetate and dichloromethane fractions significantly alleviated liver injury in rats as indicated by the reduced levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (TB), and malondialdehyde (MDA), along with enhancement of the total antioxidant capacities of their livers, with the maximum effects were recorded by the ethyl acetate fraction. Moreover, the protective actions of both fractions were comparable to those of silymarin (100 mg/kg), and have been also substantiated by histopathological evaluations. On the other hand, liquid chromatography-high resolution electrospray ionization mass spectrometry (LC‒HR‒ESI‒MS) metabolomic profiling of the crude extract of M. arboreus aerial parts showed the presence of a variety of phytochemicals, mostly phenolics, whereas the detailed chemical analysis of the most active fraction (i.e. ethyl acetate) resulted in the isolation and identification of six compounds for the first time in the genus, comprising four phenolic acids; β-resorcylic, caffeic, protocatechuic, and 4-hydroxyphenylacetic acids, in addition to two flavonoids; trifolin and astragalin. Such phenolic principles, together with their probable synergistic antioxidant and liver-protecting properties, seem to contribute to the observed hepatoprotective potential of M. arboreus.}, language = {en} } @article{KaluzaWallaceHeardetal.2018, author = {Kaluza, Benjamin F. and Wallace, Helen M. and Heard, Tim A. and Minden, Vanessa and Klein, Alexandra and Leonhardt, Sara D.}, title = {Social bees are fitter in more biodiverse environments}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {12353}, doi = {10.1038/s41598-018-30126-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177231}, year = {2018}, abstract = {Bee population declines are often linked to human impacts, especially habitat and biodiversity loss, but empirical evidence is lacking. To clarify the link between biodiversity loss and bee decline, we examined how floral diversity affects (reproductive) fitness and population growth of a social stingless bee. For the first time, we related available resource diversity and abundance to resource (quality and quantity) intake and colony reproduction, over more than two years. Our results reveal plant diversity as key driver of bee fitness. Social bee colonies were fitter and their populations grew faster in more florally diverse environments due to a continuous supply of food resources. Colonies responded to high plant diversity with increased resource intake and colony food stores. Our findings thus point to biodiversity loss as main reason for the observed bee decline.}, language = {en} } @article{KienleGarridoBreitenbachChudejetal.2018, author = {Kienle-Garrido, Melina-Lor{\´e}n and Breitenbach, Tim and Chudej, Kurt and Borz{\`i}, Alfio}, title = {Modeling and numerical solution of a cancer therapy optimal control problem}, series = {Applied Mathematics}, volume = {9}, journal = {Applied Mathematics}, number = {8}, doi = {10.4236/am.2018.98067}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177152}, pages = {985-1004}, year = {2018}, abstract = {A mathematical optimal-control tumor therapy framework consisting of radio- and anti-angiogenesis control strategies that are included in a tumor growth model is investigated. The governing system, resulting from the combination of two well established models, represents the differential constraint of a non-smooth optimal control problem that aims at reducing the volume of the tumor while keeping the radio- and anti-angiogenesis chemical dosage to a minimum. Existence of optimal solutions is proved and necessary conditions are formulated in terms of the Pontryagin maximum principle. Based on this principle, a so-called sequential quadratic Hamiltonian (SQH) method is discussed and benchmarked with an "interior point optimizer―a mathematical programming language" (IPOPT-AMPL) algorithm. Results of numerical experiments are presented that successfully validate the SQH solution scheme. Further, it is shown how to choose the optimisation weights in order to obtain treatment functions that successfully reduce the tumor volume to zero.}, language = {en} } @article{HefnerBerberichLanversetal.2018, author = {Hefner, Jochen and Berberich, Sara and Lanvers, Elena and Sanning, Maria and Steimer, Ann-Kathrin and Kunzmann, Volker}, title = {Patient-doctor relationship and adherence to capecitabine in outpatients of a German comprehensive cancer center}, series = {Patient Preference and Adherence}, volume = {12}, journal = {Patient Preference and Adherence}, doi = {10.2147/PPA.S169354}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177143}, pages = {1875—1887}, year = {2018}, abstract = {Purpose: The prescribing of oral chemotherapy agents has introduced the new challenge of ensuring patients' adherence to therapy. Aspects of a close patient-doctor relationship are reported to be correlated with adherence to oral anticancer drugs, but data on capecitabine are scarce. Patients and methods: Sixty-four outpatients with a diagnosis of cancer and prescribed capecitabine were recruited from a German Comprehensive Cancer Center. We used the Patient-Doctor Relationship Questionnaire (PDRQ-9), the Medical Adherence Rating Scale (MARS), the Beliefs about Medicines Questionnaire (BMQ), and the Satisfaction with Information about Medicines Scale (SIMS) to assess patients' perceptions and behavior. Medical data were extracted from the charts. Results: Non-adherence was reported by 20\% of the 64 participants. The perceived quality of the patient-doctor relationship was high in general, but it did not emerge as a predictor of adherence in our survey (odds ratio [OR]=0.915, P=0.162, 95\% CI=0.808-1.036). However, beliefs about medicine (OR=1.268, P<0.002; 95\% CI=1.090-1.475) as well as satisfaction with information about medicine (OR=1.252, P<0.040, 95\% CI=1.010-1.551) were predictors of adherence and the quality of the patient-doctor relationship was correlated with both variables (r=0.373, P=0.002 for SIMS sum score; r=0.263, P=0.036 for BMQ necessity/concern difference). Overall, adherence to capecitabine was high with a conviction that the therapy is necessary. However, concerns were expressed regarding the long-term effect of capecitabine use. Patients have unmet information needs regarding interactions of capecitabine with other medicines and the impairment of their intimate life. Conclusions: In order to ensure adherence to capecitabine, our results seem to encourage the default use of modern and perhaps more impersonal means of information brokerage (eg, email, internet). However, the contents of some of patients' informational needs as well as the associations of patients' beliefs and satisfaction about the information received suggest a benefit from a trustful patient-doctor relationship.}, language = {en} } @article{FoerstnerReuscherHaberzettletal.2018, author = {F{\"o}rstner, Konrad U and Reuscher, Carina M and Haberzettl, Kerstin and Weber, Lennart and Klug, Gabriele}, title = {RNase E cleavage shapes the transcriptome of Rhodobacter sphaeroides and strongly impacts phototrophic growth}, series = {Life Science Alliance}, volume = {1}, journal = {Life Science Alliance}, number = {4}, doi = {10.26508/lsa.201800080}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177139}, pages = {e201800080}, year = {2018}, abstract = {Bacteria adapt to changing environmental conditions by rapid changes in their transcriptome. This is achieved not only by adjusting rates of transcription but also by processing and degradation of RNAs. We applied TIER-Seq (transiently inactivating an endoribonuclease followed by RNA-Seq) for the transcriptome-wide identification of RNase E cleavage sites and of 5′ RNA ends, which are enriched when RNase E activity is reduced in Rhodobacter sphaeroides. These results reveal the importance of RNase E for the maturation and turnover of mRNAs, rRNAs, and sRNAs in this guanine-cytosine-rich α-proteobacterium, some of the latter have well-described functions in the oxidative stress response. In agreement with this, a role of RNase E in the oxidative stress response is demonstrated. A remarkably strong phenotype of a mutant with reduced RNase E activity was observed regarding the formation of photosynthetic complexes and phototrophic growth, whereas there was no effect on chemotrophic growth.}, language = {en} } @article{ZoltnerKrienitzFieldetal.2018, author = {Zoltner, Martin and Krienitz, Nina and Field, Mark C. and Kramer, Susanne}, title = {Comparative proteomics of the two T. brucei PABPs suggests that PABP2 controls bulk mRNA}, series = {PLoS Neglected Tropical Diseases}, volume = {12}, journal = {PLoS Neglected Tropical Diseases}, number = {7}, doi = {10.1371/journal.pntd.0006679}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177126}, pages = {e0006679}, year = {2018}, abstract = {Poly(A)-binding proteins (PABPs) regulate mRNA fate by controlling stability and translation through interactions with both the poly(A) tail and eIF4F complex. Many organisms have several paralogs of PABPs and eIF4F complex components and it is likely that different eIF4F/PABP complex combinations regulate distinct sets of mRNAs. Trypanosomes have five eIF4G paralogs, six of eIF4E and two PABPs, PABP1 and PABP2. Under starvation, polysomes dissociate and the majority of mRNAs, most translation initiation factors and PABP2 reversibly localise to starvation stress granules. To understand this more broadly we identified a protein interaction cohort for both T. brucei PABPs by cryo-mill/affinity purification-mass spectrometry. PABP1 very specifically interacts with the previously identified interactors eIF4E4 and eIF4G3 and few others. In contrast PABP2 is promiscuous, with a larger set of interactors including most translation initiation factors and most prominently eIF4G1, with its two partners TbG1-IP and TbG1-IP2. Only RBP23 was specific to PABP1, whilst 14 RNA-binding proteins were exclusively immunoprecipitated with PABP2. Significantly, PABP1 and associated proteins are largely excluded from starvation stress granules, but PABP2 and most interactors translocate to granules on starvation. We suggest that PABP1 regulates a small subpopulation of mainly small-sized mRNAs, as it interacts with a small and distinct set of proteins unable to enter the dominant pathway into starvation stress granules and localises preferentially to a subfraction of small polysomes. By contrast PABP2 likely regulates bulk mRNA translation, as it interacts with a wide range of proteins, enters stress granules and distributes over the full range of polysomes.}, language = {en} } @article{YuVogelFoerstner2018, author = {Yu, Sung-Huan and Vogel, J{\"o}rg and F{\"o}rstner, Konrad U.}, title = {ANNOgesic: a Swiss army knife for the RNA-seq based annotation of bacterial/archaeal genomes}, series = {GigaScience}, volume = {7}, journal = {GigaScience}, doi = {10.1093/gigascience/giy096}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178942}, year = {2018}, abstract = {To understand the gene regulation of an organism of interest, a comprehensive genome annotation is essential. While some features, such as coding sequences, can be computationally predicted with high accuracy based purely on the genomic sequence, others, such as promoter elements or noncoding RNAs, are harder to detect. RNA sequencing (RNA-seq) has proven to be an efficient method to identify these genomic features and to improve genome annotations. However, processing and integrating RNA-seq data in order to generate high-resolution annotations is challenging, time consuming, and requires numerous steps. We have constructed a powerful and modular tool called ANNOgesic that provides the required analyses and simplifies RNA-seq-based bacterial and archaeal genome annotation. It can integrate data from conventional RNA-seq and differential RNA-seq and predicts and annotates numerous features, including small noncoding RNAs, with high precision. The software is available under an open source license (ISCL) at https://pypi.org/project/ANNOgesic/.}, language = {en} } @article{WernerMarcusSheikhbahaeietal.2018, author = {Werner, Rudolf A. and Marcus, Charles and Sheikhbahaei, Sara and Solnes, Lilja B. and Leal, Jeffrey P. and Du, Yong and Rowe, Steven P. and Higuchi, Takahiro and Buck, Andreas K. and Lapa, Constantin and Javadi, Mehrbod S.}, title = {Visual and Semiquantitative Accuracy in Clinical Baseline 123I-Ioflupane SPECT/CT Imaging}, series = {Clinical Nuclear Medicine}, volume = {44}, journal = {Clinical Nuclear Medicine}, number = {1}, issn = {1536-0229}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168181}, year = {2018}, abstract = {PURPOSE: We aimed to (a) elucidate the concordance of visual assessment of an initial I-ioflupane scan by a human interpreter with comparison to results using a fully automatic semiquantitative method and (b) to assess the accuracy compared to follow-up (f/u) diagnosis established by movement disorder specialists. METHODS: An initial I-ioflupane scan was performed in 382 patients with clinically uncertain Parkinsonian syndrome. An experienced reader performed a visual evaluation of all scans independently. The findings of the visual read were compared with semiquantitative evaluation. In addition, available f/u clinical diagnosis (serving as a reference standard) was compared with results of the human read and the software. RESULTS: When comparing the semiquantitative method with the visual assessment, discordance could be found in 25 (6.5\%) of 382 of the cases for the experienced reader (ĸ = 0.868). The human observer indicated region of interest misalignment as the main reason for discordance. With neurology f/u serving as reference, the results of the reader revealed a slightly higher accuracy rate (87.7\%, ĸ = 0.75) compared to semiquantification (86.2\%, ĸ = 0.719, P < 0.001, respectively). No significant difference in the diagnostic performance of the visual read versus software-based assessment was found. CONCLUSIONS: In comparison with a fully automatic semiquantitative method in I-ioflupane interpretation, human assessment obtained an almost perfect agreement rate. However, compared to clinical established diagnosis serving as a reference, visual read seemed to be slightly more accurate as a solely software-based quantitative assessment.}, subject = {SPECT}, language = {en} } @article{RedlichMartinWendeetal.2018, author = {Redlich, Sarah and Martin, Emily A. and Wende, Beate and Steffan-Dewenter, Ingolf}, title = {Landscape heterogeneity rather than crop diversity mediates bird diversity in agricultural landscapes}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0200438}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177110}, pages = {e0200438}, year = {2018}, abstract = {Crop diversification has been proposed as farm management tool that could mitigate the externalities of conventional farming while reducing productivity-biodiversity trade-offs. Yet evidence for the acclaimed biodiversity benefits of landscape-level crop diversity is ambiguous. Effects may strongly depend on spatial scale and the level of landscape heterogeneity (e.g. overall habitat diversity). At the same time, contrasting within-taxon responses obscure benefits to specific functional groups (i.e. species with shared characteristics or requirements) if studied at the community level. The objectives of this study were to 1) disentangle the relative effects of crop diversity and landscape heterogeneity on avian species richness across five spatial scales ranging from 250 to 3000 m radii around focal winter wheat fields; and 2) assess whether functional groups (feeding guild, conservation status, habitat preference, nesting behaviour) determine the strength and direction of responses to crop diversity and landscape heterogeneity. In central Germany, 14 landscapes were selected along independent gradients of crop diversity (annual arable crops) and landscape heterogeneity. Bird species richness in each landscape was estimated using four point counts throughout the breeding season. We found no effects of landscape-level crop diversity on bird richness and functional groups. Instead, landscape heterogeneity was strongly associated with increased total bird richness across all spatial scales. In particular, insect-feeding and non-farmland birds were favoured in heterogeneous landscapes, as were species not classified as endangered or vulnerable on the regional Red List. Crop-nesting farmland birds, however, were less species-rich in these landscapes. Accordingly, crop diversification may be less suitable for conserving avian diversity and associated ecosystem services (e.g. biological pest control), although confounding interactions with management intensity need yet to be confirmed. In contrast, enhancement of landscape heterogeneity by increasing perennial habitat diversity, reducing field sizes and the amount of cropland has the potential to benefit overall bird richness. Specialist farmland birds, however, may require more targeted management approaches.}, language = {en} } @article{BankogluArnoldHeringetal.2018, author = {Bankoglu, Ezgi Eyluel and Arnold, Charlotte and Hering, Ilona and Hankir, Mohammed and Seyfried, Florian and Stopper, Helga}, title = {Decreased chromosomal damage in lymphocytes of obese patients after bariatric surgery}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {11195}, doi = {10.1038/s41598-018-29581-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177090}, year = {2018}, abstract = {The number of bariatric surgeries being performed worldwide has markedly risen. While the improvement in obesity-associated comorbidities after bariatric surgery is well-established, very little is known about its impact on cancer risk. The peripheral lymphocyte micronucleus test is a widely used method for the monitoring of chromosomal damage levels in vivo, and micronucleus frequency positively correlates with cancer risk. Therefore, the aim of this study was to compare the micronucleus frequency before and after bariatric surgery in obese subjects. Peripheral blood mononuclear cells were collected from 45 obese subjects before and at two time-points after bariatric surgery (6 and 12 months) to assess spontaneous micronucleus frequency. Consistent with the increased cancer risk previously shown, bariatric surgery-induced weight loss led to a significant reduction in lymphocyte micronucleus frequency after 12 months. Interestingly, comorbidities such as type 2 diabetes mellitus and metabolic syndrome further seemed to have an impact on the lymphocyte micronucleus frequency. Our findings may indicate a successful reduction of cancer risk in patients following weight loss caused by bariatric surgery.}, language = {en} } @unpublished{StennettMattockPentecostetal.2018, author = {Stennett, Tom and Mattock, James and Pentecost, Leanne and Vargas, Alfredo and Braunschweig, Holger}, title = {Chelated Diborenes and their Inverse-Electron-Demand Diels- Alder Reactions with Dienes}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201809217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178268}, year = {2018}, abstract = {A doubly base-stabilized diborane based on a benzylphosphine linker was prepared by a salt elimination reaction between 2-LiC\(_6\)H\(_4\)CH\(_2\)PCy\(_2\).Et\(_2\)O and B\(_2\)Br\(_4\). This compound was reduced with KC8 to its corresponding diborene, with the benzylphosphine forming a five-membered chelate. The diborene reacts with butadiene, 2-trimethylsiloxy-1,3-butadiene and isoprene to form 4,5-diboracyclohexenes, which interconvert between their 1,1- (geminal) and 1,2- (vicinal) chelated isomers. The 1,1-chelated diborene undergoes a halide-catalysed isomerisation into its thermodynamically favoured 1,2-isomer, which undergoes Diels-Alder reactions more slowly than the kinetic product.}, language = {en} } @unpublished{StennettBertermannBraunschweig2018, author = {Stennett, Tom and Bertermann, R{\"u}diger and Braunschweig, Holger}, title = {Construction of Linear and Branched Tetraboranes via 1,1- and 1,2-Diboration of Diborenes}, series = {Angewandte Chemie, International Edition}, journal = {Angewandte Chemie, International Edition}, doi = {10.1002/anie.201809976}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178276}, year = {2018}, abstract = {Sterically unencumbered diborenes based on a benzylphosphine chelate undergo diboration reactions with bis(catecholato)diboron in the absence of a catalyst to yield tetraboranes. The symmetrical diborenes studied undergo 1,2- diborations, whereas an unsymmetrical derivative was found to yield a triborylborane-phosphine adduct as the result of a formal 1,1-diboration. A related borylborylene compound also underwent a 1,2-diboration to produce a borylene-borane adduct.}, language = {en} } @article{SchlichtingRiegerCusumanoetal.2018, author = {Schlichting, Matthias and Rieger, Dirk and Cusumano, Paola and Grebler, Rudi and Costa, Rodolfo and Mazzotta, Gabriella M. and Helfrich-F{\"o}rster, Charlotte}, title = {Cryptochrome interacts with actin and enhances eye-mediated light sensitivity of the circadian clock in Drosophila melanogaster}, series = {Frontiers in Molecular Neuroscience}, volume = {11}, journal = {Frontiers in Molecular Neuroscience}, number = {238}, doi = {10.3389/fnmol.2018.00238}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177086}, year = {2018}, abstract = {Cryptochromes (CRYs) are a class of flavoproteins that sense blue light. In animals, CRYs are expressed in the eyes and in the clock neurons that control sleep/wake cycles and are implied in the generation and/or entrainment of circadian rhythmicity. Moreover, CRYs are sensing magnetic fields in insects as well as in humans. Here, we show that in the fruit fly Drosophila melanogaster CRY plays a light-independent role as "assembling" protein in the rhabdomeres of the compound eyes. CRY interacts with actin and appears to increase light sensitivity of the eyes by keeping the "signalplex" of the phototransduction cascade close to the membrane. By this way, CRY also enhances light-responses of the circadian clock.}, language = {en} } @article{KunzeLillaStetteretal.2018, author = {Kunze, Ekkehard and Lilla, Nadine and Stetter, Christian and Ernestus, Ralf-Ingo and Westermaier, Thomas}, title = {Magnesium protects in episodes of critical perfusion after aneurysmal SAH}, series = {Translational Neuroscience}, volume = {9}, journal = {Translational Neuroscience}, number = {1}, doi = {10.1515/tnsci-2018-0016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177078}, pages = {99-105}, year = {2018}, abstract = {Background: To analyze whether magnesium has a neuroprotective effect during episodes that indicate a critical brain perfusion after aneurysmal subarachnoid hemorrhage (SAH). Methods: 107 patients with aSAH were randomized to continuously receive intravenous magnesium sulfate with target serum levels of 2.0 - 2.5 mmol/l (n = 54) or isotonic saline (n = 53). Neurological examination and transcranial Doppler sonography (TCD) were performed daily, Perfusion-CT (PCT) was acquired in 3-day intervals, angiography in case of suspected vasospasm. The primary endpoint was the development of secondary infarction following episodes of delayed ischemic neurological deficit (DIND), elevated mean flow velocity (MFV) in TCD or pathological findings in PCT. Results: In the magnesium group, 9 episodes of DIND were registered, none was followed by secondary infarction. In the control group, 23 episodes of DIND were registered, 9 were followed by secondary infarction (p < 0.05). In the magnesium group, 114 TCD-measurements showed an elevated MFV(> 140 cm/s). 7 were followed by new infarction. In control patients, 135 measurements showed elevated MFV, 32 were followed by new infarction (p < 0.05). 10 of 117 abnormal PCT-findings were followed by new infarction, compared to 30 of 122 in the control-group (p < 0.05). Conclusion: DIND, elevated MFV in TCD and abnormal PCT are findings which are associated with an increased risk to develop delayed secondary infarction. The results of this analysis suggest that magnesium-treatment may reduce the risk to develop infarction in a state of critical brain perfusion.}, language = {en} } @article{RasheedHoelleinHolzgrabe2018, author = {Rasheed, Huma and H{\"o}llein, Ludwig and Holzgrabe, Ulrike}, title = {Future information technology tools for fighting substandard and falsified medicines in low- and middle-income countries}, series = {Frontiers in Pharmacology}, volume = {9}, journal = {Frontiers in Pharmacology}, number = {995}, doi = {10.3389/fphar.2018.00995}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177068}, year = {2018}, abstract = {Substandard and falsified (SF) medicines have emerged as a global public health issue within the last two decades especially in low- and middle-income countries (LMICs). Serious consequences of this problem include a loss of trust and increased financial costs due to less disease control and more frequent complications during therapy. Of note, antimicrobial resistance is an additional long-term implication of poor-quality antimicrobials. This review covers information technology tools including medicines authentication tools (MAT) as mobile apps and messaging service, 2D barcoding approaches with drug safety alert systems, web based drug safety alerts, radiofrequency identification tags, databases to support visual inspection, digital aids to enhance the performance of quality evaluation kits, reference libraries for identification of falsified and substandard medicines, and quality evaluation kits based on machine learning for field testing. While being easy to access and simple to use, these initiatives are gaining acceptance in LMICs. Implementing 2D barcoding based on end-to-end verification and "Track and Trace" systems has emerged as a step toward global security in the supply chain. A breakthrough in web-based drug safety alert systems and data bases was the establishment of the Global Surveillance and Monitoring System by the World Health Organization in 2013. Future applications include concepts including "lab on a chip" and "paper analytical devices" and are claimed to be convenient and simple to use as well as affordable. The principles discussed herein are making profound impact in the fight against substandard and falsified medicines, offering cheap and accessible solutions.}, language = {en} } @article{WurmbSchorscherJusticeetal.2018, author = {Wurmb, T and Schorscher, N and Justice, P and Dietz, S and Schua, R and Jarausch, T and Kinstle, U and Greiner, J and M{\"o}ldner, G and M{\"u}ller, J and Kraus, M and Simon, S and Wagenh{\"a}user, U and Hemm, J and Roewer, N and Helm, M}, title = {Structured analysis, evaluation and report of the emergency response to a terrorist attack in Wuerzburg, Germany using a new template of standardised quality indicators}, series = {Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine}, volume = {26}, journal = {Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine}, number = {87}, doi = {10.1186/s13049-018-0555-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177054}, year = {2018}, abstract = {Background: Until now there has been a reported lack of systematic reports and scientific evaluations of rescue missions during terror attacks. This however is urgently required in order to improve the performance of emergency medical services and to be able to compare different missions with each other. Aim of the presented work was to report the systematic evaluation and the lessons learned from the response to a terror attack that happened in Wuerzburg, Germany in 2016. Methods: A team of 14 experts developed a template of quality indicators and operational characteristics, which allow for the description, assessment and comparison of civil emergency rescue missions during mass killing incidents. The entire systematic evaluation process consisted of three main steps. The first step was the systematic data collection according to the quality indicators and operational characteristics. Second was the systematic stratification and assessment of the data. The last step was the prioritisation of the identified weaknesses and the definition of the lessons learned. Results: Five important "lessons learned" have been defined. First of all, a comprehensive concept for rescue missions during terror attacks is essential. Furthermore, the establishment of a defined high priority communication infrastructure between the different dispatch centres ("red phone") is vital. The goal is to secure the continuity of information between a few well-defined individuals. Thirdly, the organization of the incident scene needs to be commonly decided and communicated between police, medical services and fire services during the mission. A successful mission tactic requires continuous flux of reports to the on-site command post. Therefore, a predefined and common communication infrastructure for all operational forces is a crucial point. Finally, all strategies need to be extensively trained before the real life scenario hits. Conclusion: According to a systematic evaluation, we defined the lessons learned from a terror attack in 2016. Further systematic reports and academic work surrounding life threatening rescue missions and mass killing incidents are needed in order to ultimately improve such mission outcomes. In the future, a close international collaboration might help to find the best database to report and evaluate major incidents but also mass killing events.}, language = {en} } @article{FischerHeinrichs2018, author = {Fischer, Matthias and Heinrichs, Harald}, title = {Dimensions, dialectic, discourse. Three political perspectives on the sustainability of the German healthcare system}, series = {International Journal of Environmental Research and Public Health}, volume = {15}, journal = {International Journal of Environmental Research and Public Health}, number = {7}, doi = {10.3390/ijerph15071526}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177003}, pages = {1526}, year = {2018}, abstract = {This review article deals with the topic of sustainability in the German healthcare system and presents an overview of how the six articles of our research relate to one another. After introducing to the context of the research, its internal principles, and the methods applied, three perspectives are presented, each also discussed in terms of the respective literature in sustainability science and political science. The review concludes by presenting a circular model and by discussing the general limitations as well as the practical implications of our research.}, language = {en} } @article{SchusterJohannsenIsbaryetal.2018, author = {Schuster, Frank and Johannsen, Stephan and Isbary, Susanne and T{\"u}rkmeneli, Ismail and Roewer, Norbert}, title = {In vitro effects of levosimendan on muscle of malignant hyperthermia susceptible and non-susceptible swine}, series = {BMC Anesthesiology}, volume = {18}, journal = {BMC Anesthesiology}, number = {182}, doi = {10.1186/s12871-018-0644-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176991}, year = {2018}, abstract = {Background: The calcium sensitizer levosimendan is increasingly used to improve hemodynamics in patients with acutely decompensated heart failure. By binding to cardiac troponin C the conformation of the calcium-troponin C complex is stabilized, which leads to acceleration of actin-myosin crossbrigde formation and increased force generating capacity of muscle fibers. Besides indications in cardiac failure, beneficial effects of levosimendan in skeletal muscle disorders are currently evaluated. The aim of this study was to investigate differential effects of levosimendan on skeletal muscle of pigs with and without susceptibility to malignant hyperthermia (MH) in order to identify possible risks of this emerging drug for patients with predisposition to MH. Methods: Muscle bundles of 17 pigs (9 MH susceptible (MHS); 8 MH non-susceptible (MHN)) were excised under general anesthesia and examined in the tissue bath with increasing concentrations of levosimendan (0.065; 0.125; 0.5; 1.0; 10 and 50 μg/ml). Baseline tension and twitch force were monitored continuously. Data are presented as median and interquartile range. Statistical evaluation was performed using D'Agostino \& Pearson test for normal distribution and student's t test and 2-way ANOVA for differences between the groups. P < 0.05 was considered significant. Results: There were no differences between the groups concerning length, weight, initial twitch force and pre-drug resting tension of the investigated muscle strips. After an initial decrease in both groups, twitch amplitude was significantly higher in MHN (- 3.0 [- 5.2-0.2] mN) compared to MHS (- 7.5 [- 10.8- -4.5] mN) (p = 0.0034) muscle at an applied levosimendan concentration of 50 μg/ml. A marked increase in resting tension was detected following levosimendan incubation with 50 μg/ml in MHS muscle bundles (3.3 [0.9-6.1] mN) compared to MHN (- 0.7 [- 1.3-0.0] mN) (p < 0.0001). Conclusions: This in vitro investigation revealed the development of significant contractures in muscle bundles of MHS pigs after incubation with levosimendan. However, the effect appeared only at supra-therapeutic concentrations and further research is needed to determine the impact of levosimendan on MHS individuals in vivo.}, language = {en} } @article{BoelchJakuscheitDoerriesetal.2018, author = {Boelch, S. P. and Jakuscheit, A. and Doerries, S. and Fraissler, L. and Hoberg, M. and Arnholdt, J. and Rudert, M.}, title = {Periprosthetic infection is the major indication for TKA revision - experiences from a university referral arthroplasty center}, series = {BMC Musculoskeletal Disorders}, volume = {19}, journal = {BMC Musculoskeletal Disorders}, number = {395}, doi = {10.1186/s12891-018-2314-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176983}, year = {2018}, abstract = {Background: We hypothesized, that periprosthetic joint infection (PJI) accounts for the major proportion of first (primary) and repeated (secondary) Total Knee Arthroplasty revisions at our university referral arthroplasty center. Methods: One thousand one hundred forty-three revisions, performed between 2008 and 2016 were grouped into primary (55\%) and secondary (45\%) revisions. The rate of revision indications was calculated and indications were categorized by time after index operation. The odds ratios of the indications for primary versus secondary revision were calculated. Results: In the primary revision group PJI accounted for 22.3\%, instability for 20.0\%, aseptic loosening for 14.9\% and retropatellar arthrosis for 14.2\%. PJI (25.6\%) was the most common indication up to 1 year after implantation, retropatellar arthrosis (26.8\%) 1-3 years and aseptic loosening (25.6\%) more than 3 years after implantation. In the secondary revision group PJI accounted for 39.7\%, aseptic loosening for 16.2\% and instability for 13.2\%. PJI was the most common indication at any time of revision with 43.8\% up to one, 35.4\% 1-3 years and 39.4\% more the 3 years after index operation. The odds ratios in repeated revision were 2.32 times higher (p = 0.000) for PJI. For instability and retropatellar arthrosis the odds ratios were 0.60 times (p = 0.006) and 0.22 times (p = 0.000) lower. Conclusions: PJI is the most common indication for secondary TKA revision and within one year after primary TKA. Aseptical failures such as instability, retropatellar arthrosis and aseptical loosening are the predominant reasons for revision more than one year after primary TKA.}, language = {en} } @article{JohannsenSchickRoeweretal.2018, author = {Johannsen, Stephan and Schick, Martin and Roewer, Norbert and Schuster, Frank}, title = {Microdialysis and ultrasound elastography for monitoring of localized muscular reaction after pharmacological stimulation in rats}, series = {BMC Research Notes}, volume = {11}, journal = {BMC Research Notes}, number = {636}, doi = {10.1186/s13104-018-3742-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176977}, year = {2018}, abstract = {Objective: Halothane and caffeine are known to cause skeletal muscular contractions in vitro and have been proven to induce circumscribed metabolic reactions when injected into rat skeletal muscle. In this study 26 rats were investigated by either continuous application of calcium 160 mM or bolus injection of caffeine 160 mM or halothane 10\% vol via a microdialysis probe in the tibialis anterior muscle. Tissue elasticity at the injection site was monitored by ultrasound strain elastography. Aim of this study was to detect (I) changes in local lactate concentrations and (II) whether these can be attributed to a muscular contraction detected by ultrasound elastography. Results: Localized metabolic reactions were verified by increasing intramuscular lactate concentrations following continuous application of calcium (0.6 [0.3;0.6] to 3.6 [3.0;4.3] mmol/l after 60 min) and bolus application of caffeine (0.2 [0.2;0.3] to 1.6 [0.9;1.9] mmol/l after 30 min) and halothane (0.3 [0.1;0.3] to 4.7 [4.3;6.3] mmol/l after 30 min). However, ultrasound elastography did not detect any differences in tissue elasticity compared to control animals. The authors identified potential limitations of the study conditions, which might be crucial to avoid for future investigations.}, language = {en} } @article{VoelkerWeigelStrehletal.2018, author = {V{\"o}lker, Hans-Ullrich and Weigel, Michael and Strehl, Annette and Frey, Lea}, title = {Levels of uPA and PAI-1 in breast cancer and its correlation to Ki67-index and results of a 21-multigene-array}, series = {Diagnostic Pathology}, volume = {13}, journal = {Diagnostic Pathology}, number = {67}, doi = {10.1186/s13000-018-0737-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176960}, year = {2018}, abstract = {Background: Conventional parameters including Ki67, hormone receptor and Her2/neu status are used for risk stratification for breast cancer. The serine protease urokinase plasminogen activator (uPA) and the plasminogen activator inhibitor type-1 (PAI-1) play an important role in tumour invasion and metastasis. Increased concentrations in tumour tissue are associated with more aggressive potential of the disease. Multigene tests provide detailed insights into tumour biology by simultaneously testing several prognostically relevant genes. With OncotypeDX\(^{®}\), a panel of 21 genes is tested by means of quantitative real-time polymerase chain reaction. The purpose of this pilot study was to analyse whether a combination of Ki67 and uPA/PAI-1 supplies indications of the result of the multigene test. Methods: The results of Ki67, uPA/PAI-1 and OncotypeDX\(^{®}\) were analysed in 25 breast carcinomas (luminal type, pT1/2, max pN1a, G2). A statistical and descriptive analysis was performed. Results: With a proliferation index Ki67 of < 14\%, the recurrence score (RS) from the multigene test was on average in the low risk range, with an intermediate RS usually resulting if Ki67 was > 14\%. Not elevated values of uPA and PAI-1 showed a lower rate of proliferation (average 8.5\%) than carcinomas with an increase of uPA and/or PAI-1 (average 13.9\%); p = 0.054, Student's t-test. When Ki67 was > 14\% and uPA and/or PAI-1 was raised, an intermediate RS resulted. These differences were significant when compared to cases with Ki67 < 14\% with non-raised uPA/PAI-1 (p < 0.03, Student's t-test). Without taking into account the proliferative activity, an intermediate RS was also verifiable if both uPA and PAI-1 showed raised values. Conclusion: A combination of the values Ki67 and uPA/PAI-1 tended to depict the RS to be expected. From this it can be deduced that an appropriate analysis of this parameter combination may be undertaken before the multigene test in routine clinical practice. The increasing cost pressure makes it necessary to base the implementation of a multigene test on ancillary variables and to potentially leave it out if not required in the event of a certain constellation of results (Ki67 raised, uPA and PAI-1 raised).}, language = {en} } @article{PetschkeStaab2018, author = {Petschke, Danny and Staab, Torsten E.M.}, title = {DLTPulseGenerator: a library for the simulation of lifetime spectra based on detector-output pulses}, series = {SoftwareX}, volume = {7}, journal = {SoftwareX}, doi = {10.1016/j.softx.2018.04.002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176883}, pages = {122-128}, year = {2018}, abstract = {The quantitative analysis of lifetime spectra relevant in both life and materials sciences presents one of the ill-posed inverse problems and, hence, leads to most stringent requirements on the hardware specifications and the analysis algorithms. Here we present DLTPulseGenerator, a library written in native C++ 11, which provides a simulation of lifetime spectra according to the measurement setup. The simulation is based on pairs of non-TTL detector output-pulses. Those pulses require the Constant Fraction Principle (CFD) for the determination of the exact timing signal and, thus, the calculation of the time difference i.e. the lifetime. To verify the functionality, simulation results were compared to experimentally obtained data using Positron Annihilation Lifetime Spectroscopy (PALS) on pure tin.}, language = {en} } @article{BoetzlRiesSchneideretal.2018, author = {Boetzl, Fabian A. and Ries, Elena and Schneider, Gudrun and Krauss, Jochen}, title = {It's a matter of design - how pitfall trap design affects trap samples and possible predictions}, series = {PeerJ}, volume = {6}, journal = {PeerJ}, number = {e5078}, doi = {10.7717/peerj.5078}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176870}, year = {2018}, abstract = {Background: Pitfall traps are commonly used to assess ground dwelling arthropod communities. The effects of different pitfall trap designs on the trapping outcome are poorly investigated however they might affect conclusions drawn from pitfall trap data greatly. Methods: We tested four pitfall trap types which have been used in previous studies for their effectiveness: a simple type, a faster exchangeable type with an extended plastic rim plate and two types with guidance barriers (V- and X-shaped). About 20 traps were active for 10 weeks and emptied biweekly resulting in 100 trap samples. Results: Pitfall traps with guidance barriers were up to five times more effective than simple pitfall traps and trap samples resulted in more similar assemblage approximations. Pitfall traps with extended plastic rim plates did not only perform poorly but also resulted in distinct carabid assemblages with less individuals of small species and a larger variation. Discussion: Due to the obvious trait filtering and resulting altered assemblages, we suggest not to use pitfall traps with extended plastic rim plates. In comprehensive biodiversity inventories, a smaller number of pitfall traps with guidance barriers and a larger number of spatial replicates is of advantage, while due to comparability reasons, the use of simple pitfall traps will be recommended in most other cases.}, language = {en} } @article{StaabFolegatiWolfertzetal.2018, author = {Staab, Thorsten E. M. and Folegati, Paola and Wolfertz, Iris and Puska, Martti J.}, title = {Stability of Cu-precipitates in Al-Cu alloys}, series = {Applied Sciences}, volume = {8}, journal = {Applied Sciences}, number = {6}, doi = {10.3390/app8061003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176866}, pages = {1003}, year = {2018}, abstract = {We present first principle calculations on formation and binding energies for Cu and Zn as solute atoms forming small clusters up to nine atoms in Al-Cu and Al-Zn alloys. We employ a density-functional approach implemented using projector-augmented waves and plane wave expansions. We find that some structures, in which Cu atoms are closely packed on {100}-planes, turn out to be extraordinary stable. We compare the results with existing numerical or experimental data when possible. We find that Cu atoms precipitating in the form of two-dimensional platelets on {100}-planes in the fcc aluminum are more stable than three-dimensional structures consisting of the same number of Cu-atoms. The preference turns out to be opposite for Zn in Al. Both observations are in agreement with experimental observations.}, language = {en} } @article{HuerterFortCottazetal.2018, author = {H{\"u}rter, Anna-Lena and Fort, S{\´e}bastian and Cottaz, Sylvain and Hedrich, Rainer and Geiger, Dietmar and Roelfsema, M. Rob G.}, title = {Mycorrhizal lipochitinoligosaccharides (LCOs) depolarize root hairs of Medicago truncatula}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0198126}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176841}, pages = {e0198126}, year = {2018}, abstract = {Arbuscular Mycorrhiza and Root Nodule Symbiosis are symbiotic interactions with a high benefit for plant growth and crop production. Thus, it is of great interest to understand the developmental process of these symbioses in detail. We analysed very early symbiotic responses of Medicago truncatula root hair cells, by stimulation with lipochitinoligosaccharides specific for the induction of nodules (Nod-LCOs), or the interaction with mycorrhiza (Myc-LCOs). Intracellular micro electrodes were used, in combination with Ca\(^{2+}\) sensitive reporter dyes, to study the relations between cytosolic Ca\(^{2+}\) signals and membrane potential changes. We found that sulfated Myc- as well as Nod-LCOs initiate a membrane depolarization, which depends on the chemical composition of these signaling molecules, as well as the genotype of the plants that were studied. A successive application of sulfated Myc-LCOs and Nod-LCOs resulted only in a single transient depolarization, indicating that Myc-LCOs can repress plasma membrane responses to Nod-LCOs. In contrast to current models, the Nod-LCO-induced depolarization precedes changes in the cytosolic Ca\(^{2+}\) level of root hair cells. The Nod-LCO induced membrane depolarization thus is most likely independent of cytosolic Ca\(^{2+}\) signals and nuclear Ca\(^{2+}\) spiking.}, language = {en} } @article{KaltdorfTheissMarkertetal.2018, author = {Kaltdorf, Kristin Verena and Theiss, Maria and Markert, Sebastian Matthias and Zhen, Mei and Dandekar, Thomas and Stigloher, Christian and Kollmannsberger, Philipp}, title = {Automated classification of synaptic vesicles in electron tomograms of C. elegans using machine learning}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0205348}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176831}, pages = {e0205348}, year = {2018}, abstract = {Synaptic vesicles (SVs) are a key component of neuronal signaling and fulfil different roles depending on their composition. In electron micrograms of neurites, two types of vesicles can be distinguished by morphological criteria, the classical "clear core" vesicles (CCV) and the typically larger "dense core" vesicles (DCV), with differences in electron density due to their diverse cargos. Compared to CCVs, the precise function of DCVs is less defined. DCVs are known to store neuropeptides, which function as neuronal messengers and modulators [1]. In C. elegans, they play a role in locomotion, dauer formation, egg-laying, and mechano- and chemosensation [2]. Another type of DCVs, also referred to as granulated vesicles, are known to transport Bassoon, Piccolo and further constituents of the presynaptic density in the center of the active zone (AZ), and therefore are important for synaptogenesis [3]. To better understand the role of different types of SVs, we present here a new automated approach to classify vesicles. We combine machine learning with an extension of our previously developed vesicle segmentation workflow, the ImageJ macro 3D ART VeSElecT. With that we reliably distinguish CCVs and DCVs in electron tomograms of C. elegans NMJs using image-based features. Analysis of the underlying ground truth data shows an increased fraction of DCVs as well as a higher mean distance between DCVs and AZs in dauer larvae compared to young adult hermaphrodites. Our machine learning based tools are adaptable and can be applied to study properties of different synaptic vesicle pools in electron tomograms of diverse model organisms.}, language = {en} } @article{KoenigGuerreiroPeršohetal.2018, author = {K{\"o}nig, Julia and Guerreiro, Marco Alexandre and Peršoh, Derek and Begerow, Dominik and Krauss, Jochen}, title = {Knowing your neighbourhood - the effects of Epichlo{\"e} endophytes on foliar fungal assemblages in perennial ryegrass in dependence of season and land-use intensity}, series = {PeerJ}, volume = {6}, journal = {PeerJ}, number = {e4660}, doi = {10.7717/peerj.4660}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176814}, year = {2018}, abstract = {Epichlo{\"e} endophytes associated with cool-season grass species can protect their hosts from herbivory and can suppress mycorrhizal colonization of the hosts' roots. However, little is known about whether or not Epichlo{\"e} endophyte infection can also change the foliar fungal assemblages of the host. We tested 52 grassland study sites along a land-use intensity gradient in three study regions over two seasons (spring vs. summer) to determine whether Epichlo{\"e} infection of the host grass Lolium perenne changes the fungal community structure in leaves. Foliar fungal communities were assessed by Next Generation Sequencing of the ITS rRNA gene region. Fungal community structure was strongly affected by study region and season in our study, while land-use intensity and infection with Epichlo{\"e} endophytes had no significant effects. We conclude that effects on non-systemic endophytes resulting from land use practices and Epichlo{\"e} infection reported in other studies were masked by local and seasonal variability in this study's grassland sites.}, language = {en} } @article{BoelchRothArnholdtetal.2018, author = {Boelch, Sebastian P. and Roth, Magnus and Arnholdt, Joerg and Rudert, Maximilian and Luedemann, Martin}, title = {Synovial fluid aspiration should not be routinely performed during the two-stage exchange of the knee}, series = {BioMed Research International}, volume = {2018}, journal = {BioMed Research International}, number = {6720712}, doi = {10.1155/2018/6720712}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176800}, year = {2018}, abstract = {Purpose. Detection of infection persistence during the two-stage exchange of the knee for periprosthetic joint infection is challenging. Synovial fluid culture (SFC) and synovial white blood cell count (SWBCC) before joint reimplantation are widespread diagnostic means for this indication. The sensitivity and specificity of SFC and of SWBCC for infection persistence before planned reimplantation were evaluated. Methods. 94 two-stage exchanges of the knee with synovial fluid aspiration performed after a drug holiday of at least 14 days and before reimplantation or spacer exchange (planned reimplantation) were retrospectively analyzed. Only cases with at least 3 intraoperative samples at planned reimplantation were included. SFC and SWBCC were compared to pathogen detection (SFC\(_{(culture)}\)/SWBCC\(_{(culture)}\) and to histopathological signs of infection persistence (SFC\(_{(histo)}\)/SWBCC\(_{(histo)}\) from intraoperative samples at planned reimplantation. For SFC, the sensitivity and specificity were calculated. For SWBCC, the optimal cut-off value with its sensitivity and specificity was calculated with the Youden-Index. Results. Sensitivity and specificity of SFC\(_{(culture)}\) were 0.0\% and 98.9\%. Sensitivity and specificity of SFC\(_{(histo)}\) were 3.4\% and 100\%. The optimal cut-off value for SWBCC\(_{(culture)}\) was 4450 cells/μl with a sensitivity of 50.0\% and a specificity of 86.5\%. The optimal cut-off value for SWBCC\(_{(histo)}\) was 3250 cells/μl with a sensitivity of 35.7\% and a specificity of 92.9\%. Conclusion. The detection of infection persistence remains challenging and a consented approach is lacking. The results do not warrant the routine performance of SFC during the two-stage exchange at the knee. SWBCC can be used to confirm infection persistence at high cut-offs, but they only occur in few patients and are therefore inappropriate for the routine use.}, language = {en} } @article{FischerRaabe2018, author = {Fischer, Matthias and Raabe, Thomas}, title = {Animal models for Coffin-Lowry syndrome: RSK2 and nervous system dysfunction}, series = {Frontiers in Behavioral Neuroscience}, volume = {12}, journal = {Frontiers in Behavioral Neuroscience}, number = {106}, doi = {10.3389/fnbeh.2018.00106}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176799}, year = {2018}, abstract = {Loss of function mutations in the rsk2 gene cause Coffin-Lowry syndrome (CLS), which is associated with multiple symptoms including severe mental disabilities. Despite the characterization of ribosomal S6 kinase 2 (RSK2) as a protein kinase acting as a downstream effector of the well characterized ERK MAP-kinase signaling pathway, it turns out to be a challenging task to link RSK2 to specific neuronal processes dysregulated in case of mutation. Animal models such as mouse and Drosophila combine advanced genetic manipulation tools with in vivo imaging techniques, high-resolution connectome analysis and a variety of behavioral assays, thereby allowing for an in-depth analysis for gene functions in the nervous system. Although modeling mental disability in animal systems has limitations because of the complexity of phenotypes, the influence of genetic variation and species-specific characteristics at the neural circuit and behavioral level, some common aspects of RSK2 function in the nervous system have emerged, which will be presented. Only with this knowledge our understanding of the pathophysiology of CLS can be improved, which might open the door for development of potential intervention strategies.}, language = {en} } @article{BiscottiAdolfiBaruccaetal.2018, author = {Biscotti, Maria Assunta and Adolfi, Mateus Contar and Barucca, Marco and Forconi, Mariko and Pallavicini, Alberto and Gerdol, Marco and Canapa, Adriana and Schartl, Manfred}, title = {A comparative view on sex differentiation and gametogenesis genes in lungfish and coelacanths}, series = {Genome Biology and Evolution}, volume = {10}, journal = {Genome Biology and Evolution}, number = {6}, doi = {10.1093/gbe/evy101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176774}, pages = {1430-1444}, year = {2018}, abstract = {Gonadal sex differentiation and reproduction are the keys to the perpetuation of favorable gene combinations and positively selected traits. In vertebrates, several gonad development features that differentiate tetrapods and fishes are likely to be, at least in part, related to the water-to-land transition. The collection of information from basal sarcopterygians, coelacanths, and lungfishes, is crucial to improve our understanding of the molecular evolution of pathways involved in reproductive functions, since these organisms are generally regarded as "living fossils" and as the direct ancestors of tetrapods. Here, we report for the first time the characterization of >50 genes related to sex differentiation and gametogenesis in Latimeria menadoensis and Protopterus annectens. Although the expression profiles of most genes is consistent with the intermediate position of basal sarcopterygians between actinopterygian fish and tetrapods, their phylogenetic placement and presence/absence patterns often reveal a closer affinity to the tetrapod orthologs. On the other hand, particular genes, for example, the male gonad factor gsdf (Gonadal Soma-Derived Factor), provide examples of ancestral traits shared with actinopterygians, which disappeared in the tetrapod lineage.}, language = {en} } @article{SunOrtegaTanetal.2018, author = {Sun, Ping and Ortega, Gabriela and Tan, Yan and Hua, Qian and Riederer, Peter F. and Deckert, J{\"u}rgen and Schmitt-B{\"o}hrer, Angelika G.}, title = {Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system}, series = {Frontiers in Aging Neuroscience}, volume = {10}, journal = {Frontiers in Aging Neuroscience}, number = {145}, doi = {10.3389/fnagi.2018.00145}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176741}, year = {2018}, abstract = {Rats intracerebroventricularily (icv) treated with streptozotocin (STZ), shown to generate an insulin resistant brain state, were used as an animal model for the sporadic form of Alzheimer's disease (sAD). Previously, we showed in an in vivo study that 3 months after STZ icv treatment hippocampal adult neurogenesis (AN) is impaired. In the present study, we examined the effects of STZ on isolated adult hippocampal neural stem cells (NSCs) using an in vitro approach. We revealed that 2.5 mM STZ inhibits the proliferation of NSCs as indicated by reduced number and size of neurospheres as well as by less BrdU-immunoreactive NSCs. Double immunofluorescence stainings of NSCs already being triggered to start with their differentiation showed that STZ primarily impairs the generation of new neurons, but not of astrocytes. For revealing mechanisms possibly involved in mediating STZ effects we analyzed expression levels of insulin/glucose system-related molecules such as the glucose transporter (GLUT) 1 and 3, the insulin receptor (IR) and the insulin-like growth factor (IGF) 1 receptor. Applying quantitative Real time-PCR (qRT-PCR) and immunofluorescence stainings we showed that STZ exerts its strongest effects on GLUT3 expression, as GLUT3 mRNA levels were found to be reduced in NSCs, and less GLUT3-immunoreactive NSCs as well as differentiating cells were detected after STZ treatment. These findings suggest that cultured NSCs are a good model for developing new strategies to treat nerve cell loss in AD and other degenerative disorders.}, language = {en} } @article{SarukhanyanShityakovDandekar2018, author = {Sarukhanyan, Edita and Shityakov, Sergey and Dandekar, Thomas}, title = {In silico designed Axl receptor blocking drug candidates against Zika virus infection}, series = {ACS Omega}, volume = {3}, journal = {ACS Omega}, number = {5}, doi = {10.1021/acsomega.8b00223}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176739}, pages = {5281-5290}, year = {2018}, abstract = {After a large outbreak in Brazil, novel drugs against Zika virus became extremely necessary. Evaluation of virus-based pharmacological strategies concerning essential host factors brought us to the idea that targeting the Axl receptor by blocking its dimerization function could be critical for virus entry. Starting from experimentally validated compounds, such as RU-301, RU-302, warfarin, and R428, we identified a novel compound 2′ (R428 derivative) to be the most potent for this task amongst a number of alternative compounds and leads. The improved affinity of compound 2′ was confirmed by molecular docking as well as molecular dynamics simulation techniques using implicit solvation models. The current study summarizes a new possibility for inhibition of the Axl function as a potential target for future antiviral therapies.}, language = {en} } @article{LangenhorstHaackGoebetal.2018, author = {Langenhorst, Daniela and Haack, Stephanie and G{\"o}b, Selina and Uri, Anna and L{\"u}hder, Fred and Vanhove, Bernhard and H{\"u}nig, Thomas and Beyersdorf, Niklas}, title = {CD28 costimulation of T helper 1 cells enhances cytokine release in vivo}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {1060}, doi = {10.3389/fimmu.2018.01060}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176726}, year = {2018}, abstract = {Compared to naive T cells, differentiated T cells are thought to be less dependent on CD28 costimulation for full activation. To revisit the role of CD28 costimulation in mouse T cell recall responses, we adoptively transferred in vitro generated OT-II T helper (Th) 1 cells into C57BL/6 mice (Thy1.2\(^{+}\)) and then either blocked CD28-ligand interactions with Fab fragments of the anti-CD28 monoclonal antibody (mAb) E18 or deleted CD28 expression using inducible CD28 knock-out OT-II mice as T cell donors. After injection of ovalbumin protein in adjuvant into the recipient mice we observed that systemic interferon (IFN)γ release strongly depended on CD28 costimulation of the Th1 cells, while secondary clonal expansion was not reduced in the absence of CD28 costimulation. For human memory CD4\(^{+}\) T cell responses we also noted that cytokine release was reduced upon inhibition of CD28 costimulation. Together, our data highlight the so far underestimated role of CD28 costimulation for the reactivation of fully differentiated CD4\(^{+}\) T cells.}, language = {en} } @article{SuchotzkiGamer2018, author = {Suchotzki, Kristina and Gamer, Matthias}, title = {Alcohol facilitates detection of concealed identity information}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {7825}, doi = {10.1038/s41598-018-25811-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176662}, year = {2018}, abstract = {The Concealed Information Test (CIT) is a well-validated means to detect whether someone possesses certain (e.g., crime-relevant) information. The current study investigated whether alcohol intoxication during CIT administration influences reaction time (RT) CIT-effects. Two opposing predictions can be made. First, by decreasing attention to critical information, alcohol intoxication could diminish CIT-effects. Second, by hampering the inhibition of truthful responses, alcohol intoxication could increase CIT-effects. A correlational field design was employed. Participants (n = 42) were recruited and tested at a bar, where alcohol consumption was voluntary and incidental. Participants completed a CIT, in which they were instructed to hide knowledge of their true identity. BAC was estimated via breath alcohol ratio. Results revealed that higher BAC levels were correlated with higher CIT-effects. Our results demonstrate that robust CIT effects can be obtained even when testing conditions differ from typical laboratory settings and strengthen the idea that response inhibition contributes to the RT-CIT effect.}, language = {en} } @article{JanschGuentherWaideretal.2018, author = {Jansch, Charline and G{\"u}nther, Katharina and Waider, Jonas and Ziegler, Georg C. and Forero, Andrea and Kollert, Sina and Svirin, Evgeniy and P{\"u}hringer, Dirk and Kwok, Chee Keong and Ullmann, Reinhard and Maierhofer, Anna and Flunkert, Julia and Haaf, Thomas and Edenhofer, Frank and Lesch, Klaus-Peter}, title = {Generation of a human induced pluripotent stem cell (iPSC) line from a 51-year-old female with attention-deficit/hyperactivity disorder (ADHD) carrying a duplication of SLC2A3}, series = {Stem Cell Research}, volume = {28}, journal = {Stem Cell Research}, doi = {10.1016/j.scr.2018.02.005}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176654}, pages = {136-140}, year = {2018}, abstract = {Fibroblasts were isolated from a skin biopsy of a clinically diagnosed 51-year-old female attention-deficit/hyperactivity disorder (ADHD) patient carrying a duplication of SLC2A3, a gene encoding neuronal glucose transporter-3 (GLUT3). Patient fibroblasts were infected with Sendai virus, a single-stranded RNA virus, to generate transgene-free human induced pluripotent stem cells (iPSCs). SLC2A3-D2-iPSCs showed expression of pluripotency-associated markers, were able to differentiate into cells of the three germ layers in vitro and had a normal female karyotype. This in vitro cellular model can be used to study the role of risk genes in the pathogenesis of ADHD, in a patient-specific manner.}, language = {en} } @article{PfitznerMayNuechter2018, author = {Pfitzner, Christian and May, Stefan and N{\"u}chter, Andreas}, title = {Body weight estimation for dose-finding and health monitoring of lying, standing and walking patients based on RGB-D data}, series = {Sensors}, volume = {18}, journal = {Sensors}, number = {5}, doi = {10.3390/s18051311}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176642}, pages = {1311}, year = {2018}, abstract = {This paper describes the estimation of the body weight of a person in front of an RGB-D camera. A survey of different methods for body weight estimation based on depth sensors is given. First, an estimation of people standing in front of a camera is presented. Second, an approach based on a stream of depth images is used to obtain the body weight of a person walking towards a sensor. The algorithm first extracts features from a point cloud and forwards them to an artificial neural network (ANN) to obtain an estimation of body weight. Besides the algorithm for the estimation, this paper further presents an open-access dataset based on measurements from a trauma room in a hospital as well as data from visitors of a public event. In total, the dataset contains 439 measurements. The article illustrates the efficiency of the approach with experiments with persons lying down in a hospital, standing persons, and walking persons. Applicable scenarios for the presented algorithm are body weight-related dosing of emergency patients.}, language = {en} } @article{LeichtWeinigMayeretal.2018, author = {Leicht, Hans Benno and Weinig, Elke and Mayer, Beate and Viebahn, Johannes and Geier, Andreas and Rau, Monika}, title = {Ceftriaxone-induced hemolytic anemia with severe renal failure: a case report and review of literature}, series = {BMC Pharmacology and Toxicology}, volume = {19}, journal = {BMC Pharmacology and Toxicology}, number = {67}, doi = {10.1186/s40360-018-0257-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176637}, year = {2018}, abstract = {Background: Drug induced immune hemolytic anemia (DIIHA) is a rare complication and often underdiagnosed. DIIHA is frequently associated with a bad outcome, including organ failure and even death. For the last decades, ceftriaxone has been one of the most common drugs causing DIIHA, and ceftriaxone-induced immune hemolytic anemia (IHA) has especially been reported to cause severe complications and fatal outcomes. Case Presentation: A 76-year-old male patient was treated with ceftriaxone for cholangitis. Short time after antibiotic exposure the patient was referred to intensive care unit due to cardiopulmonary instability. Hemolysis was observed on laboratory testing and the patient developed severe renal failure with a need for hemodialysis for 2 weeks. Medical history revealed that the patient had been previously exposed to ceftriaxone less than 3 weeks before with subsequent hemolytic reaction. Further causes for hemolytic anemia were excluded and drug-induced immune hemolytic (DIIHA) anemia to ceftriaxone could be confirmed. Conclusions: The case demonstrates the severity of ceftriaxone-induced immune hemolytic anemia, a rare, but immediately life-threatening condition of a frequently used antibiotic in clinical practice. Early and correct diagnosis of DIIHA is crucial, as immediate withdrawal of the causative drug is essential for the patient prognosis. Thus, awareness for this complication must be raised among treating physicians.}, language = {en} } @article{VonaMaroofianBellacchioetal.2018, author = {Vona, Barbara and Maroofian, Reza and Bellacchio, Emanuele and Najafi, Maryam and Thompson, Kyle and Alahmad, Ahmad and He, Langping and Ahangari, Najmeh and Rad, Abolfazl and Shahrokhzadeh, Sima and Bahena, Paulina and Mittag, Falk and Traub, Frank and Movaffagh, Jebrail and Amiri, Nafise and Doosti, Mohammad and Boostani, Reza and Shirzadeh, Ebrahim and Haaf, Thomas and Diodato, Daria and Schmidts, Miriam and Taylor, Robert W. and Karimiani, Ehsan Ghayoor}, title = {Expanding the clinical phenotype of IARS2-related mitochondrial disease}, series = {BMC Medical Genetics}, volume = {19}, journal = {BMC Medical Genetics}, number = {196}, doi = {10.1186/s12881-018-0709-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176620}, year = {2018}, abstract = {Background: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. Methods: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. Results: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. Conclusions: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia.}, language = {en} } @article{SchuhmannEberleinMuelleretal.2018, author = {Schuhmann, Sarah and Eberlein, Uta and M{\"u}ller, Jessica and Scherthan, Harry and Lassmann, Michael}, title = {Correlation of the absorbed dose to the blood and DNA damage in leukocytes after internal ex-vivo irradiation of blood samples with Ra-224}, series = {EJNMMI Research}, volume = {8}, journal = {EJNMMI Research}, number = {77}, doi = {10.1186/s13550-018-0422-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176593}, year = {2018}, abstract = {Background: Irradiation with α-particles creates densely packed damage tracks along particle trajectories in exposed cells, including complex DNA damage and closely spaced double-strand breaks (DSBs) in hit nuclei. Here, we investigated the correlation of the absorbed dose to the blood and the number of α-induced DNA damage tracks elicited in human blood leukocytes after ex-vivo in-solution exposure with Ra-224. The aim was to compare the data to previously published data on Ra-223 and to investigate differences in DNA damage induction between the two radium isotopes. Results: Blood samples from three healthy volunteers were exposed ex-vivo to six different concentrations of Ra-224 dichloride. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the Ra-224 decay chain, ranging from 0 to 127 mGy. γ-H2AX + 53BP1 DNA damage co-staining and analysis was performed on ethanol-fixed leukocytes isolated from the irradiated blood samples. For damage quantification, α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci were enumerated in the exposed leukocytes. This revealed a linear relationship between the frequency of α-induced γ-H2AX damage tracks and the absorbed dose to the blood, while the frequency of small γ-H2AX + 53BP1 DSB foci indicative of β-irradiation was similar to baseline values. Conclusions: Our data provide a first estimation of the DNA damage induced by Ra-224 in peripheral blood mononuclear cells. A comparison with our previously published Ra-223 data suggests that there is no difference in the induction of radiation-induced DNA damage between the two radium isotopes due to their similar decay properties.}, language = {en} } @article{KottlerSchartl2018, author = {Kottler, Verena A. and Schartl, Manfred}, title = {The colorful sex chromosomes of teleost fish}, series = {Genes}, volume = {9}, journal = {Genes}, number = {5}, doi = {10.3390/genes9050233}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176587}, pages = {233}, year = {2018}, abstract = {Teleost fish provide some of the most intriguing examples of sexually dimorphic coloration, which is often advantageous for only one of the sexes. Mapping studies demonstrated that the genetic loci underlying such color patterns are frequently in tight linkage to the sex-determining locus of a species, ensuring sex-specific expression of the corresponding trait. Several genes affecting color synthesis and pigment cell development have been previously described, but the color loci on the sex chromosomes have mostly remained elusive as yet. Here, we summarize the current knowledge about the genetics of such color loci in teleosts, mainly from studies on poeciliids and cichlids. Further studies on these color loci will certainly provide important insights into the evolution of sex chromosomes.}, language = {en} } @article{BoertleinDraegerSchoenaueretal.2018, author = {B{\"o}rtlein, Charlene and Draeger, Annette and Schoenauer, Roman and Kuhlemann, Alexander and Sauer, Markus and Schneider-Schaulies, Sybille and Avota, Elita}, title = {The neutral sphingomyelinase 2 is required to polarize and sustain T Cell receptor signaling}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {815}, doi = {10.3389/fimmu.2018.00815}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176572}, year = {2018}, abstract = {By promoting ceramide release at the cytosolic membrane leaflet, the neutral sphingomyelinase 2 (NSM) is capable of organizing receptor and signalosome segregation. Its role in T cell receptor (TCR) signaling remained so far unknown. We now show that TCR-driven NSM activation is dispensable for TCR clustering and initial phosphorylation, but of crucial importance for further signal amplification. In particular, at low doses of TCR stimulatory antibodies, NSM is required for Ca\(^{2+}\) mobilization and T cell proliferation. NSM-deficient T cells lack sustained CD3ζ and ZAP-70 phosphorylation and are unable to polarize and stabilize their microtubular system. We identified PKCζ as the key NSM downstream effector in this second wave of TCR signaling supporting dynamics of microtubule-organizing center (MTOC). Ceramide supplementation rescued PKCζ membrane recruitment and MTOC translocation in NSM-deficient cells. These findings identify the NSM as essential in TCR signaling when dynamic cytoskeletal reorganization promotes continued lateral and vertical supply of TCR signaling components: CD3ζ, Zap70, and PKCζ, and functional immune synapses are organized and stabilized via MTOC polarization.}, language = {en} } @article{SperlichHahnEdeletal.2018, author = {Sperlich, Billy and Hahn, Lea-Sofie and Edel, Antonia and Behr, Tino and Helmprobst, Julian and Leppich, Robert and Wallmann-Sperlich, Birgit and Holmberg, Hans-Christer}, title = {A 4-week intervention involving mobile-based daily 6-minute micro-sessions of functional high-intensity circuit training improves strength and quality of life, but not cardio-respiratory fitness of young untrained adults}, series = {Frontiers in Physiology}, volume = {9}, journal = {Frontiers in Physiology}, number = {423}, doi = {10.3389/fphys.2018.00423}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176565}, year = {2018}, abstract = {The present study was designed to assess the psycho-physiological responses of physically untrained individuals to mobile-based multi-stimulating, circuit-like, multiple-joint conditioning (Circuit\(_{HIIT}\)) performed either once (1xCircuitHIIT) or twice (2xCircuit\(_{HIIT}\)) daily for 4 weeks. In this single-center, two-arm randomized, controlled study, 24 men and women (age: 25 ± 5 years) first received no training instructions for 4 weeks and then performed 4 weeks of either 1xCircuitHIIT or 2xCircuit\(_{HIIT}\) (5 men and 7 women in each group) daily. The 1xCircuitHIIT and 2xCircuit\(_{HIIT}\) participants carried out 90.7 and 85.7\% of all planned training sessions, respectively, with average heart rates during the 6-min sessions of 74.3 and 70.8\% of maximal heart rate. Body, fat and fat-free mass, and metabolic rate at rest did not differ between the groups or between time-points of measurement. Heart rate while running at 6 km⋅h\(^{-1}\) declined after the intervention in both groups. Submaximal and peak oxygen uptake, the respiratory exchange ratio and heart rate recovery were not altered by either intervention. The maximal numbers of push-ups, leg-levers, burpees, 45°-one-legged squats and 30-s skipping, as well as perception of general health improved in both groups. Our 1xCircuit\(_{HIIT}\) or 2xCircuit\(_{HIIT}\) interventions improved certain parameters of functional strength and certain dimensions of quality of life in young untrained individuals. However, they were not sufficient to enhance cardio-respiratory fitness, in particular peak oxygen uptake.}, language = {en} } @article{GrohHoernerMartini2018, author = {Groh, Janos and H{\"o}rner, Michaela and Martini, Rudolf}, title = {Teriflunomide attenuates neuroinflammation-related neural damage in mice carrying human PLP1 mutations}, series = {Journal of Neuroinflammation}, volume = {15}, journal = {Journal of Neuroinflammation}, number = {194}, doi = {10.1186/s12974-018-1228-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176524}, year = {2018}, abstract = {Background: Genetically caused neurological disorders of the central nervous system (CNS) are mostly characterized by poor or even fatal clinical outcome and few or no causative treatments are available. Often, these disorders are associated with low-grade, disease-promoting inflammation, another feature shared by progressive forms of multiple sclerosis (PMS). We previously generated two mouse lines carrying distinct mutations in the oligodendrocytic PLP1 gene that have initially been identified in patients diagnosed with MS. These mutations cause a loss of PLP function leading to a histopathological and clinical phenotype common to both PMS and genetic CNS disorders, like hereditary spastic paraplegias. Importantly, neuroinflammation promotes disease progression in these models, suggesting that pharmacological modulation of inflammation might ameliorate disease outcome. Methods: We applied teriflunomide, an approved medication for relapsing-remitting MS targeting activated T-lymphocytes, in the drinking water (10 mg/kg body weight/day). Experimental long-term treatment of PLP mutant mice was non-invasively monitored by longitudinal optical coherence tomography and by rotarod analysis. Immunomodulatory effects were subsequently analyzed by flow cytometry and immunohistochemistry and treatment effects regarding neural damage, and neurodegeneration were assessed by histology and immunohistochemistry. Results: Preventive treatment with teriflunomide attenuated the increase in number of CD8+ cytotoxic effector T cells and fostered the proliferation of CD8+ CD122+ PD-1+ regulatory T cells in the CNS. This led to an amelioration of axonopathic features and neuron loss in the retinotectal system, also reflected by reduced thinning of the innermost retinal composite layer in longitudinal studies and ameliorated clinical outcome upon preventive long-term treatment. Treatment of immune-incompetent PLP mutants did not provide evidence for a direct, neuroprotective effect of the medication. When treatment was terminated, no rebound of neuroinflammation occurred and histopathological improvement was preserved for at least 75 days without treatment. After disease onset, teriflunomide halted ongoing axonal perturbation and enabled a recovery of dendritic arborization by surviving ganglion cells. However, neither neuron loss nor clinical features were ameliorated, likely due to already advanced neurodegeneration before treatment onset. Conclusions: We identify teriflunomide as a possible medication not only for PMS but also for inflammation-related genetic diseases of the nervous system for which causal treatment options are presently lacking.}, language = {en} } @article{KohlRutschmann2018, author = {Kohl, Patrick Laurenz and Rutschmann, Benjamin}, title = {The neglected bee trees: European beech forests as a home for feral honey bee colonies}, series = {PeerJ}, volume = {6}, journal = {PeerJ}, number = {e4602}, doi = {10.7717/peerj.4602}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176512}, year = {2018}, abstract = {It is a common belief that feral honey bee colonies (Apis mellifera L.) were eradicated in Europe through the loss of habitats, domestication by man and spread of pathogens and parasites. Interestingly, no scientific data are available, neither about the past nor the present status of naturally nesting honeybee colonies. We expected near-natural beech (Fagus sylvatica L.) forests to provide enough suitable nest sites to be a home for feral honey bee colonies in Europe. Here, we made a first assessment of their occurrence and density in two German woodland areas based on two methods, the tracing of nest sites based on forager flight routes (beelining technique), and the direct inspection of potential cavity trees. Further, we established experimental swarms at forest edges and decoded dances for nest sites performed by scout bees in order to study how far swarms from beekeeper-managed hives would potentially move into a forest. We found that feral honey bee colonies regularly inhabit tree cavities in near-natural beech forests at densities of at least 0.11-0.14 colonies/km\(^{2}\). Colonies were not confined to the forest edges; they were also living deep inside the forests. We estimated a median distance of 2,600 m from the bee trees to the next apiaries, while scout bees in experimental swarms communicated nest sites in close distances (median: 470 m). We extrapolate that there are several thousand feral honey bee colonies in German woodlands. These have to be taken in account when assessing the role of forest areas in providing pollination services to the surrounding land, and their occurrence has implications for the species' perception among researchers, beekeepers and conservationists. This study provides a starting point for investigating the life-histories and the ecological interactions of honey bees in temperate European forest environments.}, language = {en} } @article{DuekingAchtzehnHolmbergetal.2018, author = {D{\"u}king, Peter and Achtzehn, Silvia and Holmberg, Hans-Christer and Sperlich, Billy}, title = {Integrated framework of load monitoring by a combination of smartphone applications, wearables and point-of-care testing provides feedback that allows individual responsive adjustments to activities of daily living}, series = {Sensors}, volume = {18}, journal = {Sensors}, number = {5}, doi = {10.3390/s18051632}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176506}, pages = {1632}, year = {2018}, abstract = {Athletes schedule their training and recovery in periods, often utilizing a pre-defined strategy. To avoid underperformance and/or compromised health, the external load during training should take into account the individual's physiological and perceptual responses. No single variable provides an adequate basis for planning, but continuous monitoring of a combination of several indicators of internal and external load during training, recovery and off-training as well may allow individual responsive adjustments of a training program in an effective manner. From a practical perspective, including that of coaches, monitoring of potential changes in health and performance should ideally be valid, reliable and sensitive, as well as time-efficient, easily applicable, non-fatiguing and as non-invasive as possible. Accordingly, smartphone applications, wearable sensors and point-of-care testing appear to offer a suitable monitoring framework allowing responsive adjustments to exercise prescription. Here, we outline 24-h monitoring of selected parameters by these technologies that (i) allows responsive adjustments of exercise programs, (ii) enhances performance and/or (iii) reduces the risk for overuse, injury and/or illness.}, language = {en} } @article{SchaeferFriedrichJorgensenetal.2018, author = {Sch{\"a}fer, Nadine and Friedrich, Maximilian and J{\o}rgensen, Morten Egevang and Kollert, Sina and Koepsell, Hermann and Wischmeyer, Erhard and Lesch, Klaus-Peter and Geiger, Dietmar and D{\"o}ring, Frank}, title = {Functional analysis of a triplet deletion in the gene encoding the sodium glucose transporter 3, a potential risk factor for ADHD}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0205109}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176495}, pages = {e0205109}, year = {2018}, abstract = {Sodium-glucose transporters (SGLT) belong to the solute carrier 5 family, which is characterized by sodium dependent transport of sugars and other solutes. In contrast, the human SGLT3 (hSGLT3) isoform, encoded by SLC5A4, acts as a glucose sensor that does not transport sugar but induces membrane depolarization by Na\(^{+}\) currents upon ligand binding. Whole-exome sequencing (WES) of several extended pedigrees with high density of attention-deficit/hyperactivity disorder (ADHD) identified a triplet ATG deletion in SLC5A4 leading to a single amino acid loss (ΔM500) in the hSGLT3 protein imperfectly co-segregating with the clinical phenotype of ADHD. Since mutations in homologous domains of hSGLT1 and hSGLT2 were found to affect intestinal and renal function, respectively, we analyzed the functional properties of hSGLT3[wt] and [ΔM500] by voltage clamp and current clamp recordings from cRNA-injected Xenopus laevis oocytes. The cation conductance of hSGLT3[wt] was activated by application of glucose or the specific agonist 1-desoxynojirimycin (DNJ) as revealed by inward currents in the voltage clamp configuration and cell depolarization in the current clamp mode. Almost no currents and changes in membrane potential were observed when glucose or DNJ were applied to hSGLT3[ΔM500]-injected oocytes, demonstrating a loss of function by this amino acid deletion in hSGLT3. To monitor membrane targeting of wt and mutant hSGLT3, fusion constructs with YFP were generated, heterologously expressed in Xenopus laevis oocytes and analyzed for membrane fluorescence by confocal microscopy. In comparison to hSGLT3[wt] the fluorescent signal of mutant [ΔM500] was reduced by 43\% indicating that the mutant phenotype might mainly result from inaccurate membrane targeting. As revealed by homology modeling, residue M500 is located in TM11 suggesting that in addition to the core structure (TM1-TM10) of the transporter, the surrounding TMs are equally crucial for transport/sensor function. In conclusion, our findings indicate that the deletion [ΔM500] in hSGLT3 inhibits membrane targeting and thus largely disrupts glucose-induced sodium conductance, which may, in interaction with other ADHD risk-related gene variants, influence the risk for ADHD in deletion carriers.}, language = {en} } @article{GilbertEdenMeffertetal.2018, author = {Gilbert, F. and Eden, L. and Meffert, R. and Konietschke, F. and Lotz, J. and Bauer, L. and Staab, W.}, title = {Intra- and interobserver reliability of glenoid fracture classifications by Ideberg, Euler and AO}, series = {BMC Musculoskeletal Disorders}, volume = {19}, journal = {BMC Musculoskeletal Disorders}, number = {89}, doi = {10.1186/s12891-018-2016-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176482}, year = {2018}, abstract = {Background: Representing 3\%-5\% of shoulder girdle injuries scapula fractures are rare. Furthermore, approximately 1\% of scapula fractures are intraarticularfractures of the glenoid fossa. Because of uncertain fracture morphology and limited experience, the treatment of glenoid fossa fractures is difficult. The glenoid fracture classification by Ideberg (1984) and Euler (1996) is still commonly used in literature. In 2013 a new glenoid fracture classification was introduced by the AO. The purpose of this study was to examine the new AO classification in clinical practice in comparison with the classifications by Ideberg and Euler. Methods: In total CT images of 84 patients with glenoid fossa fractures from 2005 to 2018 were included. Parasagittal, paracoronary and axial reconstructions were examined according to the classifications of Ideberg, Euler and the AO by 3 investigators (orthopedic surgeon, radiologist, student of medicine) at three individual time settings. Inter- and intraobserver reliability of the three classification systems were ascertained by computing Inter- and Intraclass (ICCs) correlation coefficients using Spearman's rank correlation coefficient, 95\%-confidence intervals as well as F-tests for correlation coefficients. Results: Inter- and intraobserver reliability for the AO classification showed a perspicuous coherence (R = 0.74 and R = 0.79). Low to moderate intraobserver reliability for Ideberg (R = 0.46) and Euler classification (R = 0.41) was found. Furthermore, data show a low Interobserver reliability for both Ideberg and Euler classification (R < 0.2). Both the Inter- and Intraclass reliability using AO is significantly higher than those using Ideberg and Euler (p < 0.05). Using the new AO classification, it was possible to find a proper class for every glenoid fossa fracture. On average, according to Euler classification 10 of 84 fractures were not classifiable whereas to Ideberg classification 21 of 84 fractures were not classifiable. Conclusion: The new AO classification system introduced 2013 facilitates reliable grading of glenoid fossa fractures with high inter- and intraobserver reliability in 84 patients using CT images. It should possibly be applied in order to enable a valid, reliable and consistent academic description of glenoid fossa fractures. The established classifications by Euler and Ideberg are not capable of providing a similar reliability.}, language = {en} } @article{HennigMichalskiRutkowskietal.2018, author = {Hennig, Thomas and Michalski, Marco and Rutkowski, Andrzej J. and Djakovic, Lara and Whisnant, Adam W. and Friedl, Marie-Sophie and Jha, Bhaskar Anand and Baptista, Marisa A. P. and L'Hernault, Anne and Erhard, Florian and D{\"o}lken, Lars and Friedel, Caroline C.}, title = {HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes}, series = {PLoS Pathogens}, volume = {14}, journal = {PLoS Pathogens}, number = {3}, doi = {10.1371/journal.ppat.1006954}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176350}, pages = {e1006954}, year = {2018}, abstract = {Lytic herpes simplex virus 1 (HSV-1) infection triggers disruption of transcription termination (DoTT) of most cellular genes, resulting in extensive intergenic transcription. Similarly, cellular stress responses lead to gene-specific transcription downstream of genes (DoG). In this study, we performed a detailed comparison of DoTT/DoG transcription between HSV-1 infection, salt and heat stress in primary human fibroblasts using 4sU-seq and ATAC-seq. Although DoTT at late times of HSV-1 infection was substantially more prominent than DoG transcription in salt and heat stress, poly(A) read-through due to DoTT/DoG transcription and affected genes were significantly correlated between all three conditions, in particular at earlier times of infection. We speculate that HSV-1 either directly usurps a cellular stress response or disrupts the transcription termination machinery in other ways but with similar consequences. In contrast to previous reports, we found that inhibition of Ca\(^{2+}\) signaling by BAPTA-AM did not specifically inhibit DoG transcription but globally impaired transcription. Most importantly, HSV-1-induced DoTT, but not stress-induced DoG transcription, was accompanied by a strong increase in open chromatin downstream of the affected poly(A) sites. In its extent and kinetics, downstream open chromatin essentially matched the poly(A) read-through transcription. We show that this does not cause but rather requires DoTT as well as high levels of transcription into the genomic regions downstream of genes. This raises intriguing new questions regarding the role of histone repositioning in the wake of RNA Polymerase II passage downstream of impaired poly(A) site recognition.}, language = {en} } @article{KressBaurOttoetal.2018, author = {Kress, Sebastian and Baur, Johannes and Otto, Christoph and Burkard, Natalie and Braspenning, Joris and Walles, Heike and Nickel, Joachim and Metzger, Marco}, title = {Evaluation of a miniaturized biologically vascularized scaffold in vitro and in vivo}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {4719}, doi = {10.1038/s41598-018-22688-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176343}, year = {2018}, abstract = {In tissue engineering, the generation and functional maintenance of dense voluminous tissues is mainly restricted due to insufficient nutrient supply. Larger three-dimensional constructs, which exceed the nutrient diffusion limit become necrotic and/or apoptotic in long-term culture if not provided with an appropriate vascularization. Here, we established protocols for the generation of a pre-vascularized biological scaffold with intact arterio-venous capillary loops from rat intestine, which is decellularized under preservation of the feeding and draining vascular tree. Vessel integrity was proven by marker expression, media/blood reflow and endothelial LDL uptake. In vitro maintenance persisted up to 7 weeks in a bioreactor system allowing a stepwise reconstruction of fully vascularized human tissues and successful in vivo implantation for up to 4 weeks, although with time-dependent decrease of cell viability. The vascularization of the construct lead to a 1.5× increase in cellular drug release compared to a conventional static culture in vitro. For the first time, we performed proof-of-concept studies demonstrating that 3D tissues can be maintained within a miniaturized vascularized scaffold in vitro and successfully implanted after re-anastomosis to the intrinsic blood circulation in vivo. We hypothesize that this technology could serve as a powerful platform technology in tissue engineering and regenerative medicine.}, language = {en} } @article{MarischenEnglertSchmittetal.2018, author = {Marischen, Lothar and Englert, Anne and Schmitt, Anna-Lena and Einsele, Hermann and Loeffler, Juergen}, title = {Human NK cells adapt their immune response towards increasing multiplicities of infection of Aspergillus fumigatus}, series = {BMC Immunology}, volume = {19}, journal = {BMC Immunology}, number = {39}, doi = {10.1186/s12865-018-0276-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176331}, year = {2018}, abstract = {Background: The saprophytic fungus Aspergillus fumigatus reproduces by generation of conidia, which are spread by airflow throughout nature. Since humans are inhaling certain amounts of spores every day, the (innate) immune system is constantly challenged. Even though macrophages and neutrophils carry the main burden, also NK cells are regarded to contribute to the antifungal immune response. While NK cells reveal a low frequency, expression and release of immunomodulatory molecules seem to be a natural way of their involvement. Results: In this study we show, that NK cells secrete chemokines such as CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES early on after stimulation with Aspergillus fumigatus and, in addition, adjust the concentration of chemokines released to the multiplicity of infection of Aspergillus fumigatus. Conclusions: These results further corroborate the relevance of NK cells within the antifungal immune response, which is regarded to be more and more important in the development and outcome of invasive aspergillosis in immunocompromised patients after hematopoietic stem cell transplantation. Additionally, the correlation between the multiplicity of infection and the expression and release of chemokines shown here may be useful in further studies for the quantification and/or surveillance of the NK cell involvement in antifungal immune responses.}, language = {en} } @article{TauscherNakagawaVoelkeretal.2018, author = {Tauscher, Sabine and Nakagawa, Hitoshi and V{\"o}lker, Katharina and Werner, Franziska and Krebes, Lisa and Potapenko, Tamara and Doose, S{\"o}ren and Birkenfeld, Andreas L. and Baba, Hideo A. and Kuhn, Michaela}, title = {β Cell-specific deletion of guanylyl cyclase A, the receptor for atrial natriuretic peptide, accelerates obesity-induced glucose intolerance in mice}, series = {Cardiovascular Diabetology}, volume = {17}, journal = {Cardiovascular Diabetology}, number = {103}, doi = {10.1186/s12933-018-0747-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176322}, year = {2018}, abstract = {Background: The cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2 diabetes and its cardiometabolic complications. In vitro, synthetic ANP, via GC-A, stimulates glucose-dependent insulin release from cultured pancreatic islets and β-cell proliferation. However, the relevance for systemic glucose homeostasis in vivo is not known. To dissect whether the endogenous cardiac hormones modulate the secretory function and/or proliferation of β-cells under (patho)physiological conditions in vivo, here we generated a novel genetic mouse model with selective disruption of the GC-A receptor in β-cells. Methods: Mice with a floxed GC-A gene were bred to Rip-CreTG mice, thereby deleting GC-A selectively in β-cells (β GC-A KO). Weight gain, glucose tolerance, insulin sensitivity, and glucose-stimulated insulin secretion were monitored in normal diet (ND)- and high-fat diet (HFD)-fed mice. β-cell size and number were measured by immunofluorescence-based islet morphometry. Results: In vitro, the insulinotropic and proliferative actions of ANP were abolished in islets isolated from β GC-A KO mice. Concordantly, in vivo, infusion of BNP mildly enhanced baseline plasma insulin levels and glucose-induced insulin secretion in control mice. This effect of exogenous BNP was abolished in β GC-A KO mice, corroborating the efficient inactivation of the GC-A receptor in β-cells. Despite this under physiological, ND conditions, fasted and fed insulin levels, glucose-induced insulin secretion, glucose tolerance and β-cell morphology were similar in β GC-A KO mice and control littermates. However, HFD-fed β GC-A KO animals had accelerated glucose intolerance and diminished adaptative β-cell proliferation. Conclusions: Our studies of β GC-A KO mice demonstrate that the cardiac hormones ANP and BNP do not modulate β-cell's growth and secretory functions under physiological, normal dietary conditions. However, endogenous NP/GC-A signaling improves the initial adaptative response of β-cells to HFD-induced obesity. Impaired β-cell NP/GC-A signaling in obese individuals might contribute to the development of type 2 diabetes.}, language = {en} } @article{GilbertJakubietzMeffertetal.2018, author = {Gilbert, Fabian and Jakubietz, Rafael G. and Meffert, Rainer H. and Jakubietz, Michael G.}, title = {Does distal radio-ulnar joint configuration affect postoperative functional results after ulnar shortening osteotomy?}, series = {PRS Global Open}, volume = {6}, journal = {PRS Global Open}, number = {4}, doi = {10.1097/GOX.0000000000001760}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176265}, pages = {e1760}, year = {2018}, abstract = {Background: Reverse oblique distal radio-ulnar joint (DRUJ) configuration is assumed to show inferior postoperative results in ulnar-shortening osteotomy due to osteoarthritis, as the joint force pressure in the DRUJ may be increased. An evaluation and comparison of the postoperative functional results with regard to clinical and radiographic signs of arthritis among different DRUJ configurations was carried out retrospectively. Methods: Sixty-two patients after ulnar shortening osteotomy were included. The minimum follow-up was 5 years. Preoperative x-rays were assessed for the DRUJ configuration according to the Tolat classification, whereas postoperative radiographs were evaluated with regard to signs of osteoarthritis using the Kallgren-Lawrence-Score. Functional results were evaluated using the disabilities of the arm, shoulder and hand (DASH) and Mayo Wrist Score and measuring range of motion and grip strength. Results: Significantly better functional results were found in patients with parallel configuration of the DRUJ (Tolat type 1 configuration) with regard to DASH score, grip strength, and supination compared with nonparallel configurations. In the Tolat type 1, configurated DRUJ mean DASH score was 9 compared with 18 in the Tolat type 2 and 3 groups. Apart from supination, no differences were observed in range of motion among groups. Conclusion: Although long-term postoperative range of motion failed to display statistically significant differences between DRUJ configurations except for supination, better results regarding grip strength and DASH scores were seen in a parallel-aligned DRUJ configuration. Although onset of osteoarthritis does not seem to become apparent within the observation period, nonparallel aligned configuration predisposes to inferior results.}, language = {en} } @article{GilbertSchneemannScholzetal.2018, author = {Gilbert, F. and Schneemann, C. and Scholz, C. J. and Kickuth, R. and Meffert, R. H. and Wildenauer, R. and Lorenz, U. and Kellersmann, R. and Busch, A.}, title = {Clinical implications of fracture-associated vascular damage in extremity and pelvic trauma}, series = {BMC Muscuskeletal Disorders}, volume = {19}, journal = {BMC Muscuskeletal Disorders}, number = {404}, doi = {10.1186/s12891-018-2333-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176252}, year = {2018}, abstract = {Background: Vascular damage in polytrauma patients is associated with high mortality and morbidity. Therefore, specific clinical implications of vascular damage with fractures in major trauma patients are reassessed. Methods: This comprehensive nine-year retrospective single center cohort study analyzed demography, laboratory, treatment and outcome data from 3689 patients, 64 patients with fracture-associated vascular injuries were identified and were compared to a control group. Results: Vascular damage occurred in 7\% of patients with upper and lower limb and pelvic fractures admitted to the trauma room. Overall survival was 80\% in pelvic fracture and 97\% in extremity fracture patients and comparable to non-vascular trauma patients. Additional arterial damage required substantial fluid administration and was visible as significantly anemia and disturbed coagulation tests upon admission. Open procedures were done in over 80\% of peripheral extremity vascular damage. Endovascular procedures were predominant (87\%) in pelvic injury. Conclusion: Vascular damage is associated with high mortality rates especially in combination with pelvic fractures. Initial anemia, disturbed coagulation tests and the need for extensive pre-clinical fluid substitution were observed in the cohort with vascular damage. Therefore, fast diagnosis and early interventional and surgical procedures are necessary to optimize patient-specific outcome.}, language = {en} } @article{VonaHofrichterSchroederetal.2018, author = {Vona, Barbara and Hofrichter, Michaela A. H. and Schr{\"o}der, J{\"o}rg and Shehata-Dieler, Wafaa and Nanda, Indrajit and Haaf, Thomas}, title = {Hereditary hearing loss SNP-microarray pilot study}, series = {BMC Research Notes}, volume = {11}, journal = {BMC Research Notes}, number = {391}, doi = {10.1186/s13104-018-3466-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176239}, year = {2018}, abstract = {Objectives: Despite recent advancements in diagnostic tools, the genomic landscape of hereditary hearing loss remains largely uncharacterized. One strategy to understand genome-wide aberrations includes the analysis of copy number variation that can be mapped using SNP-microarray technology. A growing collection of literature has begun to uncover the importance of copy number variation in hereditary hearing loss. This pilot study underpins a larger effort that involves the stage-wise analysis of hearing loss patients, many of whom have advanced to high-throughput sequencing analysis. Data description: Our data originate from the Infinium HumanOmni1-Quad v1.0 SNP-microarrays (Illumina) that provide useful markers for genome-wide association studies and copy number variation analysis. This dataset comprises a cohort of 108 individuals (99 with hearing loss, 9 normal hearing family members) for the purpose of understanding the genetic contribution of copy number variations to hereditary hearing loss. These anonymized SNP-microarray data have been uploaded to the NCBI Gene Expression Omnibus and are intended to benefit other investigators interested in aggregating platform-matched array patient datasets or as part of a supporting reference tool for other laboratories to better understand recurring copy number variations in other genetic disorders.}, language = {en} } @article{StrobelJohswich2018, author = {Strobel, Lea and Johswich, Kay O.}, title = {Anticoagulants impact on innate immune responses and bacterial survival in whole blood models of Neisseria meningitidis infection}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {10225}, doi = {10.1038/s41598-018-28583-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176226}, year = {2018}, abstract = {Neisseria meningitidis (meningococcus) causes invasive diseases such as meningitis or septicaemia. Ex vivo infection of human whole blood is a valuable tool to study meningococcal virulence factors and the host innate immune responses. In order to consider effects of cellular mediators, the coagulation cascade must be inhibited to avoid clotting. There is considerable variation in the anticoagulants used among studies of N. meningitidis whole blood infections, featuring citrate, heparin or derivatives of hirudin, a polypeptide from leech saliva. Here, we compare the influence of these three different anticoagulants, and additionally Mg/EGTA, on host innate immune responses as well as on viability of N. meningitidis strains isolated from healthy carriers and disease cases, reflecting different sequence types and capsule phenotypes. We found that the anticoagulants significantly impact on cellular responses and, strain-dependently, also on bacterial survival. Hirudin does not inhibit complement and is therefore superior over the other anticoagulants; indeed hirudin-plasma most closely reflects the characteristics of serum during N. meningitidis infection. We further demonstrate the impact of heparin on complement activation on N. meningitidis and its consequences on meningococcal survival in immune sera, which appears to be independent of the heparin binding antigens Opc and NHBA.}, language = {en} } @article{HintzscheMontagStopper2018, author = {Hintzsche, Henning and Montag, Gracia and Stopper, Helga}, title = {Induction of micronuclei by four cytostatic compounds in human hematopoietic stem cells and human lymphoblastoid TK6 cells}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {3371}, doi = {10.1038/s41598-018-21680-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176210}, year = {2018}, abstract = {For mutagenicity testing, primary lymphocytes or mammalian cell lines are employed. However, the true target for carcinogenic action of mutagenic chemicals may be stem cells. Since hematopoietic cancers induced by chemical agents originate at the hematopoietic stem cell (HSC) stage and since one of the side effects of chemotherapeutic cancer treatment is the induction of secondary tumors, often leukemias, HSC may be a suitable cell system. We compared the sensitivity of HSC with the genotoxicity testing cell line TK6 for chromosomal mutations. HSC were less sensitive than TK6 cells for the genotoxic effects of the model genotoxins and chemotherapeutic agents doxorubicin, vinblastine, methyl methanesulfonate (MMS) and equally sensitive for mitomycin C (MMC). However, loss of viability after mitomycin C treatment was higher in HSC than in TK6 cells. Among the factors that may influence sensitivity for genomic damage, the generation or response to reactive oxygen species (ROS) and the effectiveness of DNA damage response can be discussed. Here we show that HSC can be used in a standard micronucleus test protocol for chromosomal mutations and that their sensitivity was not higher than that of a classical testing cell line.}, language = {en} } @article{DuekingFussHolmbergetal.2018, author = {D{\"u}king, Peter and Fuss, Franz Konstantin and Holmberg, Hans-Christer and Sperlich, Billy}, title = {Recommendations for assessment of the reliability, sensitivity, and validity of data provided by wearable sensors designed for monitoring physical activity}, series = {JMIR Mhealth and Uhealth}, volume = {6}, journal = {JMIR Mhealth and Uhealth}, number = {4}, doi = {10.2196/mhealth.9341}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176202}, pages = {e102}, year = {2018}, abstract = {Although it is becoming increasingly popular to monitor parameters related to training, recovery, and health with wearable sensor technology (wearables), scientific evaluation of the reliability, sensitivity, and validity of such data is limited and, where available, has involved a wide variety of approaches. To improve the trustworthiness of data collected by wearables and facilitate comparisons, we have outlined recommendations for standardized evaluation. We discuss the wearable devices themselves, as well as experimental and statistical considerations. Adherence to these recommendations should be beneficial not only for the individual, but also for regulatory organizations and insurance companies.}, language = {en} } @article{BenoitScheurlenGoebeleretal.2018, author = {Benoit, Sandrine and Scheurlen, Michael and Goebeler, Matthias and Stoevesandt, Johanna}, title = {Structured diagnostic approach and risk assessment in mucous membrane pemphigoid with oesophageal involvement}, series = {Acta Dermato-Venereologica}, volume = {98}, journal = {Acta Dermato-Venereologica}, doi = {10.2340/00015555-2938}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176191}, pages = {660-666}, year = {2018}, abstract = {Oesophageal involvement in mucous membrane pemphigoid is considered rare, but it may be underdiagnosed. To assess the incidence of oesophageal involvement in a group of patients with newly diagnosed mucous membrane pemphigoid we retrospectively analysed the medical records of 30 consecutive patients with mucous membrane pemphigoid diagnosed between 2006 and 2016 at the Department of Dermatology, University Hospital W{\"u}rzburg. Twenty-one patients (70\%) reported symptoms indicative of oesophageal mucous membrane pemphigoid. Twelve patients (40\%) underwent oesophagogastroduodenoscopy, and oesophageal pathology compatible with mucous membrane pemphigoid was endoscopically found in 9 cases (30\%). In all patients indirect and direct immunofluorescence were performed. Patients with and without oesophageal involvement did not differ with regard to the results of indirect immunofluorescence on salt-split human skin and monkey oesophagus. Study results demonstrate the necessity of a standardized diagnostic work-up, including adequate tissue samples for direct immunofluorescence, to prevent underdiagnosis of oesophageal mucous membrane pemphigoid.}, language = {en} } @article{PelzWagnerLichthardtetal.2018, author = {Pelz, J{\"o}rg O. W. and Wagner, Johanna and Lichthardt, Sven and Baur, Johannes and Kastner, Caroline and Matthes, Niels and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Laparoscopic right-sided colon resection for colon cancer - has the control group so far been chosen correctly?}, series = {World Journal of Surgical Oncology}, volume = {16}, journal = {World Journal of Surgical Oncology}, number = {117}, doi = {10.1186/s12957-018-1417-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176186}, year = {2018}, abstract = {Background: The treatment strategies for colorectal cancer located in the right side of the colon have changed dramatically during the last decade. Due to the introduction of complete mesocolic excision (CME) with central ligation of the vessels and systematic lymph node dissection, the long-term survival of affected patients has increased significantly. It has also been proposed that right-sided colon resection can be performed laparoscopically with the same extent of resection and equal long-term results. Methods: A retrospective evaluation of a prospectively expanded database on right-sided colorectal cancer or adenoma treated at the University Hospital of Wuerzburg between 2009 and 2016 was performed. All patients underwent CME. This data was analyzed alone and in comparison to the published data describing laparoscopic right-sided colon resection for colon cancer. Results: The database contains 279 patients, who underwent right-sided colon resection due to colorectal cancer or colorectal adenoma (255 open; 24 laparoscopic). Operation data (time, length of stay, time on ICU) was equal or superior to laparoscopy, which is comparable to the published results. Surprisingly, the surrogate parameter for correct CME (the number of removed lymph nodes) was significantly higher in the open group. In a subgroup analysis only including patients who were feasible for laparoscopic resection and had been operated with an open procedure by an experienced surgeon, operation time was significantly shorter and the number of removed lymph nodes is significantly higher in the open group. Conclusion: So far, several studies demonstrate that laparoscopic right-sided colon resection is comparable to open resection. Our data suggests that a consequent CME during an open operation leads to significantly more removed lymph nodes than in laparoscopically resected patients and in several so far published data of open control groups from Europe. Further prospective randomized trials comparing the long-term outcome are urgently needed before laparoscopy for right-sided colon resection can be recommended ubiquitously.}, language = {en} } @article{DuekingHolmbergSperlich2018, author = {D{\"u}king, Peter and Holmberg, Hans-Christer and Sperlich, Billy}, title = {The potential usefulness of virtual reality systems for athletes: a short SWOT analysis}, series = {Frontiers in Physiology}, volume = {9}, journal = {Frontiers in Physiology}, number = {128}, doi = {10.3389/fphys.2018.00128}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176178}, year = {2018}, abstract = {No abstract available.}, language = {en} } @article{WegenerSauer2018, author = {Wegener, Sonja and Sauer, Otto A.}, title = {Electrometer offset current due to scattered radiation}, series = {Journal of Applied Clinical Medical Physics}, volume = {19}, journal = {Journal of Applied Clinical Medical Physics}, number = {6}, doi = {10.1002/acm2.12458}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176137}, pages = {274-281}, year = {2018}, abstract = {Relative dose measurements with small ionization chambers in combination with an electrometer placed in the treatment room ("internal electrometer") show a large dependence on the polarity used. While this was observed previously for percent depth dose curves (PDDs), the effect has not been understood or preventable. To investigate the polarity dependence of internal electrometers used in conjunction with a small-volume ionization chamber, we placed an internal electrometer at a distance of 1 m from the isocenter and exposed it to different amounts of scattered radiation by varying the field size. We identified irradiation of the electrometer to cause a current of approximately -1 pA, regardless of the sign of the biasing voltage. For low-sensitivity detectors, such a current noticeably distorts relative dose measurements. To demonstrate how the current systematically changes PDDs, we collected measurements with nine ionization chambers of different volumes. As the chamber volume decreased, signal ratios at 20 and 10 cm depth (M20/M10) became smaller for positive bias voltage and larger for negative bias voltage. At the size of the iba CC04 (40 mm\(^{3}\)) the difference of M20/M10 was around 1\% and for the smallest studied chamber, the iba CC003 chamber (3 mm\(^{3}\)), around 7\% for a 10 × 10 cm² field. When the electrometer was moved further from the source or shielded, the additional current decreased. Consequently, PDDs at both polarities were brought into alignment at depth even for the 3 mm\(^{3}\) ionization chamber. The apparent polarity effect on PDDs and lateral beam profiles was reduced considerably by shielding the electrometer. Due to normalization the effect on output values was low. When measurements with a low-sensitivity probe are carried out in conjunction with an internal electrometer, we recommend careful monitoring of the particular setup by testing both polarities, and if deemed necessary, we suggest shielding the electrometer.}, language = {en} } @article{SimonIpekHomolaetal.2018, author = {Simon, Micha and Ipek, Rojda and Homola, Gy{\"o}rgy A. and Rovituso, Damiano M. and Schampel, Andrea and Kleinschnitz, Christoph and Kuerten, Stefanie}, title = {Anti-CD52 antibody treatment depletes B cell aggregates in the central nervous system in a mouse model of multiple sclerosis}, series = {Journal of Neuroinflammation}, volume = {15}, journal = {Journal of Neuroinflammation}, number = {225}, doi = {10.1186/s12974-018-1263-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176120}, year = {2018}, abstract = {Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) for which several new treatment options were recently introduced. Among them is the monoclonal anti-CD52 antibody alemtuzumab that depletes mainly B cells and T cells in the immune periphery. Considering the ongoing controversy about the involvement of B cells and in particular the formation of B cell aggregates in the brains of progressive MS patients, an in-depth understanding of the effects of anti-CD52 antibody treatment on the B cell compartment in the CNS itself is desirable. Methods: We used myelin basic protein (MBP)-proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 (B6) mice as B cell-dependent model of MS. Mice were treated intraperitoneally either at the peak of EAE or at 60 days after onset with 200 μg murine anti-CD52 vs. IgG2a isotype control antibody for five consecutive days. Disease was subsequently monitored for 10 days. The antigen-specific B cell/antibody response was measured by ELISPOT and ELISA. Effects on CNS infiltration and B cell aggregation were determined by immunohistochemistry. Neurodegeneration was evaluated by Luxol Fast Blue, SMI-32, and Olig2/APC staining as well as by electron microscopy and phosphorylated heavy neurofilament serum ELISA. Results: Treatment with anti-CD52 antibody attenuated EAE only when administered at the peak of disease. While there was no effect on the production of MP4-specific IgG, the treatment almost completely depleted CNS infiltrates and B cell aggregates even when given as late as 60 days after onset. On the ultrastructural level, we observed significantly less axonal damage in the spinal cord and cerebellum in chronic EAE after anti-CD52 treatment. Conclusion: Anti-CD52 treatment abrogated B cell infiltration and disrupted existing B cell aggregates in the CNS.}, language = {en} } @article{GilbertMeffertSchmalzletal.2018, author = {Gilbert, F. and Meffert, R. H. and Schmalzl, J. and Weng, A. M. and K{\"o}stler, H. and Eden, L.}, title = {Grade of retraction and tendon thickness correlates with MR-spectroscopically measured amount of fatty degeneration in full thickness supraspinatus tears}, series = {BMC Musculoskeletal Disorders}, volume = {19}, journal = {BMC Musculoskeletal Disorders}, number = {197}, doi = {10.1186/s12891-018-2096-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176116}, year = {2018}, abstract = {Background: The amount of fatty degeneration (FD) has major impact on the clinical result and cuff integrity after rotator cuff repair. A quantitative analysis with magnet resonance imaging (MRI) spectroscopy was employed to analyze possible correlation of FD with tendon retraction, tendon thickness and patients' characteristics in full thickness supraspinatus tears. Methods: Forty-two patients with full-thickness supraspinatus tears underwent shoulder MRI including an experimental spectroscopic sequence allowing quantification of the fat fraction in the supraspinatus muscle belly. The amount of fatty degeneration was correlated with tendon retraction, tendon thickness, patients' age, gender, smoker status, symptom duration and body mass index (BMI). Patients were divided in to three groups of retraction (A) 0-10 mm (n=), (B) 11-20 mm (n=) and (C) < 21 mm (n=) and the means of FD for each group were calculated. Results: Tendon retraction (R = 0.6) and symptom duration (R = 0.6) correlated positively, whereas tendon thickness correlated negatively (R = - 0.6) with the amount of FD. The fat fraction increased significantly with tendon retraction: Group (A) showed a mean fat mount of 3.7\% (±4\%), group (B) of 16.7\% (±8.2\%) and group (C) of 37.5\% (±19\%). BMI, age and smoker-status only showed weak to moderate correlation with the amount of FD in this cohort. Conclusion: MRI spectroscopy revealed significantly higher amount of fat with increasing grade of retraction, symptom duration and decreased tendon thickness. Thus, these parameters may indirectly be associated with the severity of tendon disease.}, language = {en} } @article{RazinskasBiagioniHecht2018, author = {Razinskas, Gary and Biagioni, Paolo and Hecht, Bert}, title = {Limits of Kirchhoff's laws in plasmonics}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {1921}, doi = {10.1038/s41598-018-20239-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176080}, year = {2018}, abstract = {The validity of Kirchhoff's laws in plasmonic nanocircuitry is investigated by studying a junction of plasmonic two-wire transmission lines. We find that Kirchhoff's laws are valid for sufficiently small values of a phenomenological parameter κ relating the geometrical parameters of the transmission line with the effective wavelength of the guided mode. Beyond such regime, for large values of the phenomenological parameter, increasing deviations occur and the equivalent impedance description (Kirchhoff's laws) can only provide rough, but nevertheless useful, guidelines for the design of more complex plasmonic circuitry. As an example we investigate a system composed of a two-wire transmission line and a nanoantenna as the load. By addition of a parallel stub designed according to Kirchhoff's laws we achieve maximum signal transfer to the nanoantenna.}, language = {en} } @article{ReichertvonRottkayRothetal.2018, author = {Reichert, Johannes C. and von Rottkay, Eberhard and Roth, Franz and Renz, Tim and Hausmann, Johannes and Kranz, Julius and Rackwitz, Lars and N{\"o}th, Ulrich and Rudert, Maximilian}, title = {A prospective randomized comparison of the minimally invasive direct anterior and the transgluteal approach for primary total hip arthroplasty}, series = {BMC Musculoskeletal Disorders}, volume = {19}, journal = {BMC Musculoskeletal Disorders}, number = {241}, doi = {10.1186/s12891-018-2133-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176072}, year = {2018}, abstract = {Background: The presented prospective randomized controlled single-centre study compares the clinical outcome up to 12 months after total hip arthroplasty using a minimally invasive single-incision direct anterior (DAA) and a direct transgluteal lateral approach. Methods: A total of 123 arthroplasties were evaluated utilizing the Harris Hip Score (HHS), the extra short musculoskeletal functional assessment questionnaire (XSFMA), the Short Form 36 (SF-36) health survey, a Stepwatch™ Activity Monitor (SAM), and a timed 25 m foot walk (T25-FW). Postoperative x-ray images after THA were reviewed to determine inclination and stem positioning. Results: At final follow-up, the XSFMA functional index scores were 10.3 (anterior) and 15.08 (lateral) while the bother index summed up to a score of 15.8 (anterior) and 21.66 (lateral) respectively, thus only differing significantly for the functional index (p = 0.040 and p = 0.056). The SF-36 physical component score (PCS) was 47.49 (anterior) and 42.91 (lateral) while the mental component score (MCS) summed up to 55.0 (anterior) and 56.23 (lateral) with a significant difference evident for the PCS (p = 0.017; p = 0.714). Patients undergoing THA through a DAA undertook a mean of 6402 cycles per day while those who had undergone THA through a transgluteal approach undertook a mean of 5340 cycles per day (p = 0.012). Furthermore, the obtained outcome for the T25-FW with 18.4 s (anterior) and 19.75 s (lateral) and the maximum walking distance (5932 m and 5125 m) differed significantly (p = 0.046 and p = 0.045). The average HHS showed no significant difference equaling 92.4 points in the anterior group and 91.43 in the lateral group (p = 0.477). The radiographic analysis revealed an average cup inclination of 38.6° (anterior) and 40.28° (lateral) without signs of migration. Conclusion: In summary, our outcomes show that after 1 year THA through the direct anterior approach results in a higher patient activity compared to THA utilizing a transgluteal lateral approach while no differences regarding hip function are evident.}, language = {en} } @unpublished{LoefflerMayerTrujilloVieraetal.2018, author = {L{\"o}ffler, Mona C. and Mayer, Alexander E. and Trujillo Viera, Jonathan and Loza Valdes, Angel and El-Merahib, Rabih and Ade, Carsten P. and Karwen, Till and Schmitz, Werner and Slotta, Anja and Erk, Manuela and Janaki-Raman, Sudha and Matesanz, Nuria and Torres, Jorge L. and Marcos, Miguel and Sabio, Guadalupe and Eilers, Martin and Schulze, Almut and Sumara, Grzegorz}, title = {Protein kinase D1 deletion in adipocytes enhances energy dissipation and protects against adiposity}, series = {The EMBO Journal}, journal = {The EMBO Journal}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176093}, year = {2018}, abstract = {Nutrient overload in combination with decreased energy dissipation promotes obesity and diabetes. Obesity results in a hormonal imbalance, which among others, activates G-protein coupled receptors utilizing diacylglycerol (DAG) as secondary messenger. Protein kinase D1 (PKD1) is a DAG effector which integrates multiple nutritional and hormonal inputs, but its physiological role in adipocytes is unknown. Here, we show that PKD1 promotes lipogenesis and suppresses mitochondrial fragmentation, biogenesis, respiration, and energy dissipation in an AMP-activated protein kinase (AMPK)-dependent manner. Moreover, mice lacking PKD1 in adipocytes are resistant to diet-induced obesity due to elevated energy expenditure. Beiging of adipocytes promotes energy expenditure and counteracts obesity. Consistently, deletion of PKD1 promotes expression of the β3-adrenergic receptor (ADRB3) in a CCAAT/enhancerbinding protein (C/EBP)-α and δ-dependent manner, which leads to the elevated expression of beige markers in adipocytes and subcutaneous adipose tissue. Finally, deletion of PKD1 in adipocytes improves insulin sensitivity and ameliorates liver steatosis. Thus, loss of PKD1 in adipocytes increases energy dissipation by several complementary mechanisms and might represent an attractive strategy to treat obesity and its related complications.}, language = {en} } @article{GeisslerJansBanaschewskietal.2018, author = {Geissler, Julia and Jans, Thomas and Banaschewski, Tobias and Becker, Katja and Renner, Tobias and Brandeis, Daniel and D{\"o}pfner, Manfred and Dose, Christina and Hautmann, Christopher and Holtmann, Martin and Jenkner, Carolin and Millenet, Sabina and Romanos, Marcel}, title = {Individualised short-term therapy for adolescents impaired by attention-deficit/hyperactivity disorder despite previous routine care treatment (ESCAadol)-Study protocol of a randomised controlled trial within the consortium ESCAlife}, series = {Trials}, volume = {19}, journal = {Trials}, number = {254}, doi = {10.1186/s13063-018-2635-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176061}, year = {2018}, abstract = {Background: Despite the high persistence rate of attention-deficit/hyperactivity disorder (ADHD) throughout the lifespan, there is a considerable gap in knowledge regarding effective treatment strategies for adolescents with ADHD. This group in particular often shows substantial psychosocial impairment, low compliance and insufficient response to psychopharmacological interventions. Effective and feasible treatments should further consider the developmental shift in ADHD symptoms, comorbidity and psychosocial adversity as well as family dysfunction. Thus, individualised interventions for adolescent ADHD should comprise a multimodal treatment strategy. The randomised controlled ESCAadol study addresses the needs of this patient group and compares the outcome of short-term cognitive behavioural therapy with parent-based telephone-assisted self-help. Methods/design: In step 1, 160 adolescents aged 12 to 17 years with a diagnosis of ADHD will undergo a treatment as usual (TAU) observation phase of 1 month. In step 2, those still severely affected are randomised to the intervention group with an Individualised Modular Treatment Programme (IMTP) or a telephone-assisted self-help programme for parents (TASH) as an active control condition. The IMTP was specifically designed for the needs of adolescent ADHD. It comprises 10 sessions of individual cognitive behavioural therapy with the adolescents and/or the parents, for which participants choose three out of 10 available focus modules (e.g. organisational skills and planning, emotion regulation, problem solving and stress management, dysfunctional family communication). TASH combines a bibliotherapeutic component with 10 counselling sessions for the parents via telephone. Primary outcome is the change in ADHD symptoms in a clinician-rated diagnostic interview. Outcomes are assessed at inclusion into the study, after the TAU phase, after the intervention phase and after a further 12-week follow-up period. The primary statistical analysis will be by intention-to-treat, using linear regression models. Additionally, we will analyse psychometric and biological predictors and moderators of treatment response. Discussion: ESCAadol compares two short-term non-pharmacological interventions as cost-efficient and feasible treatment options for adolescent ADHD, addressing the specific needs and obstacles to treatment success in this group. We aim to contribute to personalised medicine for adolescent ADHD intended to be implemented in routine clinical care.}, language = {en} } @article{DittertHuettnerPolaketal.2018, author = {Dittert, Natalie and H{\"u}ttner, Sandrina and Polak, Thomas and Herrmann, Martin J.}, title = {Augmentation of fear extinction by transcranial direct current stimulation (tDCS)}, series = {Frontiers in Behavioral Neuroscience}, volume = {12}, journal = {Frontiers in Behavioral Neuroscience}, number = {76}, doi = {10.3389/fnbeh.2018.00076}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176056}, year = {2018}, abstract = {Although posttraumatic stress disorder (PTSD; DSM-V 309.82) and anxiety disorders (DSM-V 300.xx) are widely spread mental disorders, the effectiveness of their therapy is still unsatisfying. Non-invasive brain-stimulation techniques like transcranial direct current stimulation (tDCS) might be an option to improve extinction learning, which is a main functional factor of exposure-based therapy for anxiety disorders. To examine this hypothesis, we used a fear conditioning paradigm with female faces as conditioned stimuli (CS) and a 95-dB female scream as unconditioned stimulus (UCS). We aimed to perform a tDCS of the ventromedial prefrontal cortex (vmPFC), which is mainly involved in the control of extinction-processes. Therefore, we applied two 4 × 4 cm electrodes approximately at the EEG-positions F7 and F8 and used a direct current of 1.5 mA. The 20-min stimulation was started during a 10-min break between acquisition and extinction and went on overall extinction-trials. The healthy participants were randomly assigned in two double-blinded process into two sham stimulation and two verum stimulation groups with opposite current flow directions. To measure the fear reactions, we used skin conductance responses (SCR) and subjective ratings. We performed a generalized estimating equations model for the SCR to assess the impact of tDCS and current flow direction on extinction processes for all subjects that showed a successful conditioning (N = 84). The results indicate that tDCS accelerates early extinction processes with a significantly faster loss of CS+/CS- discrimination. The discrimination loss was driven by a significant decrease in reaction toward the CS+ as well as an increase in reaction toward the CS- in the tDCS verum groups, whereas the sham groups showed no significant reaction changes during this period. Therefore, we assume that tDCS of the vmPFC can be used to enhance early extinction processes successfully. But before it should be tested in a clinical context further investigation is needed to assess the reason for the reaction increase on CS-. If this negative side effect can be avoided, tDCS may be a tool to improve exposure-based anxiety therapies.}, language = {en} } @article{FichtnerKarunakaranStaricketal.2018, author = {Fichtner, Alina Suzann and Karunakaran, Mohindar Murugesh and Starick, Lisa and Truman, Richard W. and Herrmann, Thomas}, title = {The armadillo (Dasypus novemcinctus): a witness but not a functional example for the emergence of the butyrophilin 3/Vγ9Vδ2 system in placental mammals}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {265}, doi = {10.3389/fimmu.2018.00265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176044}, year = {2018}, abstract = {1-5\% of human blood T cells are Vγ9Vδ2 T cells whose T cell receptor (TCR) contain a TRGV9/TRGJP rearrangement and a TRDV2 comprising Vδ2-chain. They respond to phosphoantigens (PAgs) like isopentenyl pyrophosphate or (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMBPP) in a butyrophilin 3 (BTN3)-dependent manner and may contribute to the control of mycobacterial infections. These cells were thought to be restricted to primates, but we demonstrated by analysis of genomic databases that TRGV9, TRDV2, and BTN3 genes coevolved and emerged together with placental mammals. Furthermore, we identified alpaca (Vicugna pacos) as species with typical Vγ9Vδ2 TCR rearrangements and currently aim to directly identify Vγ9Vδ2 T cells and BTN3. Other candidates to study this coevolution are the bottlenose dolphin (Tursiops truncatus) and the nine-banded armadillo (Dasypus novemcinctus) with genomic sequences encoding open reading frames for TRGV9, TRDV2, and the extracellular part of BTN3. Dolphins have been shown to express Vγ9- and Vδ2-like TCR chains and possess a predicted BTN3-like gene homologous to human BTN3A3. The other candidate, the armadillo, is of medical interest since it serves as a natural reservoir for Mycobacterium leprae. In this study, we analyzed the armadillo genome and found evidence for multiple non-functional BTN3 genes including genomic context which closely resembles the organization of the human, alpaca, and dolphin BTN3A3 loci. However, no BTN3 transcript could be detected in armadillo cDNA. Additionally, attempts to identify a functional TRGV9/TRGJP rearrangement via PCR failed. In contrast, complete TRDV2 gene segments preferentially rearranged with a TRDJ4 homolog were cloned and co-expressed with a human Vγ9-chain in murine hybridoma cells. These cells could be stimulated by immobilized anti-mouse CD3 antibody but not with human RAJI-RT1Bl cells and HMBPP. So far, the lack of expression of TRGV9 rearrangements and BTN3 renders the armadillo an unlikely candidate species for PAg-reactive Vγ9Vδ2 T cells. This is in line with the postulated coevolution of the three genes, where occurrence of Vγ9Vδ2 TCRs coincides with a functional BTN3 molecule.}, language = {en} } @article{SilwedelSpeerHaarmannetal.2018, author = {Silwedel, Christine and Speer, Christian P. and Haarmann, Axel and Fehrholz, Markus and Claus, Heike and Buttmann, Mathias and Glaser, Kirsten}, title = {Novel insights into neuroinflammation: bacterial lipopolysaccharide, tumor necrosis factor α, and Ureaplasma species differentially modulate atypical chemokine receptor 3 responses in human brain microvascular endothelial cells}, series = {Journal of Neuroinflammation}, volume = {15}, journal = {Journal of Neuroinflammation}, number = {156}, doi = {10.1186/s12974-018-1170-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175952}, year = {2018}, abstract = {Background: Atypical chemokine receptor 3 (ACKR3, synonym CXCR7) is increasingly considered relevant in neuroinflammatory conditions, in which its upregulation contributes to compromised endothelial barrier function and may ultimately allow inflammatory brain injury. While an impact of ACKR3 has been recognized in several neurological autoimmune diseases, neuroinflammation may also result from infectious agents, including Ureaplasma species (spp.). Although commonly regarded as commensals of the adult urogenital tract, Ureaplasma spp. may cause invasive infections in immunocompromised adults as well as in neonates and appear to be relevant pathogens in neonatal meningitis. Nonetheless, clinical and in vitro data on Ureaplasma-induced inflammation are scarce. Methods: We established a cell culture model of Ureaplasma meningitis, aiming to analyze ACKR3 variances as a possible pathomechanism in Ureaplasma-associated neuroinflammation. Non-immortalized human brain microvascular endothelial cells (HBMEC) were exposed to bacterial lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α), and native as well as LPS-primed HBMEC were cultured with Ureaplasma urealyticum serovar 8 (Uu8) and U. parvum serovar 3 (Up3). ACKR3 responses were assessed via qRT-PCR, RNA sequencing, flow cytometry, and immunocytochemistry. Results: LPS, TNF-α, and Ureaplasma spp. influenced ACKR3 expression in HBMEC. LPS and TNF-α significantly induced ACKR3 mRNA expression (p < 0.001, vs. control), whereas Ureaplasma spp. enhanced ACKR3 protein expression in HBMEC (p < 0.01, vs. broth control). Co-stimulation with LPS and either Ureaplasma isolate intensified ACKR3 responses (p < 0.05, vs. LPS). Furthermore, stimulation wielded a differential influence on the receptor's ligands. Conclusions: We introduce an in vitro model of Ureaplasma meningitis. We are able to demonstrate a pro-inflammatory capacity of Ureaplasma spp. in native and, even more so, in LPS-primed HBMEC, underlining their clinical relevance particularly in a setting of co-infection. Furthermore, our data may indicate a novel role for ACKR3, with an impact not limited to auto-inflammatory diseases, but extending to infection-related neuroinflammation as well. AKCR3-induced blood-brain barrier breakdown might constitute a potential common pathomechanism.}, language = {en} } @article{KruegerEngstler2018, author = {Kr{\"u}ger, Timothy and Engstler, Markus}, title = {The fantastic voyage of the trypanosome: a protean micromachine perfected during 500 million years of engineering}, series = {Micromachines}, volume = {9}, journal = {Micromachines}, number = {2}, doi = {10.3390/mi9020063}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175944}, pages = {63}, year = {2018}, abstract = {The human body is constantly attacked by pathogens. Various lines of defence have evolved, among which the immune system is principal. In contrast to most pathogens, the African trypanosomes thrive freely in the blood circulation, where they escape immune destruction by antigenic variation and incessant motility. These unicellular parasites are flagellate microswimmers that also withstand the harsh mechanical forces prevailing in the bloodstream. They undergo complex developmental cycles in the bloodstream and organs of the mammalian host, as well as the disease-transmitting tsetse fly. Each life cycle stage has been shaped by evolution for manoeuvring in distinct microenvironments. Here, we introduce trypanosomes as blueprints for nature-inspired design of trypanobots, micromachines that, in the future, could explore the human body without affecting its physiology. We review cell biological and biophysical aspects of trypanosome motion. While this could provide a basis for the engineering of microbots, their actuation and control still appear more like fiction than science. Here, we discuss potentials and challenges of trypanosome-inspired microswimmer robots.}, language = {en} } @article{KropfRoessler2018, author = {Kropf, Jan and R{\"o}ssler, Wolfgang}, title = {In-situ recording of ionic currents in projection neurons and Kenyon cells in the olfactory pathway of the honeybee}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0191425}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175869}, pages = {e0191425}, year = {2018}, abstract = {The honeybee olfactory pathway comprises an intriguing pattern of convergence and divergence: ~60.000 olfactory sensory neurons (OSN) convey olfactory information on ~900 projection neurons (PN) in the antennal lobe (AL). To transmit this information reliably, PNs employ relatively high spiking frequencies with complex patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB). This pathway comprises the medial (m-ALT) and the lateral antennal lobe tract (l-ALT). PNs from both tracts transmit information from a wide range of similar odors, but with distinct differences in coding properties. In the MBs, PNs form synapses with many Kenyon cells (KC) that encode odors in a spatially and temporally sparse way. The transformation from complex information coding to sparse coding is a well-known phenomenon in insect olfactory coding. Intrinsic neuronal properties as well as GABAergic inhibition are thought to contribute to this change in odor representation. In the present study, we identified intrinsic neuronal properties promoting coding differences between PNs and KCs using in-situ patch-clamp recordings in the intact brain. We found very prominent K+ currents in KCs clearly differing from the PN currents. This suggests that odor coding differences between PNs and KCs may be caused by differences in their specific ion channel properties. Comparison of ionic currents of m- and l-ALT PNs did not reveal any differences at a qualitative level.}, language = {en} } @article{HesselbachScheiner2018, author = {Hesselbach, Hannah and Scheiner, Ricarda}, title = {Effects of the novel pesticide flupyradifurone (Sivanto) on honeybee taste and cognition}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {4954}, doi = {10.1038/s41598-018-23200-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175853}, year = {2018}, abstract = {Due to intensive agriculture honeybees are threatened by various pesticides. The use of one group of them, the neonicotinoids, was recently restricted by the European Union. These chemicals bind to the nicotinic acetylcholine receptor (nAchR) in the honeybee brain. Recently, Bayer AG released a new pesticide by the name of "Sivanto" against sucking insects. It is assumed to be harmless for honeybees, although its active ingredient, flupyradifurone, binds nAchR similar to the neonicotinoids. We investigated if this pesticide affects the taste for sugar and cognitive performance in honeybee foragers. These bees are directly exposed to the pesticide while foraging for pollen or nectar. Our results demonstrate that flupyradifurone can reduce taste and appetitive learning performance in honeybees foraging for pollen and nectar, although only the highest concentration had significant effects. Most likely, honeybee foragers will not be exposed to these high concentrations. Therefore, the appropriate use of this pesticide is considered safe for honeybees, at least with respect to the behaviors studied here.}, language = {en} } @article{SchartlSchoriesWatamatsuetal.2018, author = {Schartl, Manfred and Schories, Susanne and Watamatsu, Yuko and Nagao, Yusuke and Hashimoto, Hisashi and Bertin, Chlo{\´e} and Mourot, Brigitte and Schmidt, Cornelia and Wilhelm, Dagmar and Centanin, Lazaro and Guiguen, Yann and Herpin, Amaury}, title = {Sox5 is involved in germ-cell regulation and sex determination in medaka following co-option of nested transposable elements}, series = {BMC Biology}, volume = {16}, journal = {BMC Biology}, number = {16}, doi = {10.1186/s12915-018-0485-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175827}, year = {2018}, abstract = {Background: Sex determination relies on a hierarchically structured network of genes, and is one of the most plastic processes in evolution. The evolution of sex-determining genes within a network, by neo- or sub-functionalization, also requires the regulatory landscape to be rewired to accommodate these novel gene functions. We previously showed that in medaka fish, the regulatory landscape of the master male-determining gene dmrt1bY underwent a profound rearrangement, concomitantly with acquiring a dominant position within the sex-determining network. This rewiring was brought about by the exaptation of a transposable element (TE) called Izanagi, which is co-opted to act as a silencer to turn off the dmrt1bY gene after it performed its function in sex determination. Results: We now show that a second TE, Rex1, has been incorporated into Izanagi. The insertion of Rex1 brought in a preformed regulatory element for the transcription factor Sox5, which here functions in establishing the temporal and cell-type-specific expression pattern of dmrt1bY. Mutant analysis demonstrates the importance of Sox5 in the gonadal development of medaka, and possibly in mice, in a dmrt1bY-independent manner. Moreover, Sox5 medaka mutants have complete female-to-male sex reversal. Conclusions: Our work reveals an unexpected complexity in TE-mediated transcriptional rewiring, with the exaptation of a second TE into a network already rewired by a TE. We also show a dual role for Sox5 during sex determination: first, as an evolutionarily conserved regulator of germ-cell number in medaka, and second, by de novo regulation of dmrt1 transcriptional activity during primary sex determination due to exaptation of the Rex1 transposable element.}, language = {en} } @article{HerrmannMuenstermannStrobeletal.2018, author = {Herrmann, Johannes and Muenstermann, Marcel and Strobel, Lea and Schubert-Unkmeir, Alexandra and Woodruff, Trent M. and Gray-Owen, Scott D. and Klos, Andreas and Johswich, Kay O.}, title = {Complement C5a receptor 1 exacerbates the pathophysiology of N. meningitidis sepsis and is a potential target for disease treatment}, series = {mBio}, volume = {9}, journal = {mBio}, number = {1}, doi = {10.1128/mBio.01755-17}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175792}, pages = {e01755-17}, year = {2018}, abstract = {Sepsis caused by Neisseria meningitidis (meningococcus) is a rapidly progressing, life-threatening disease. Because its initial symptoms are rather unspecific, medical attention is often sought too late, i.e., when the systemic inflammatory response is already unleashed. This in turn limits the success of antibiotic treatment. The complement system is generally accepted as the most important innate immune determinant against invasive meningococcal disease since it protects the host through the bactericidal membrane attack complex. However, complement activation concomitantly liberates the C5a peptide, and it remains unclear whether this potent anaphylatoxin contributes to protection and/or drives the rapidly progressing immunopathogenesis associated with meningococcal disease. Here, we dissected the specific contribution of C5a receptor 1 (C5aR1), the canonical receptor for C5a, using a mouse model of meningococcal sepsis. Mice lacking C3 or C5 displayed susceptibility that was enhanced by >1,000-fold or 100-fold, respectively, consistent with the contribution of these components to protection. In clear contrast, C5ar1\(^{-/-}\) mice resisted invasive meningococcal infection and cleared N. meningitidis more rapidly than wild-type (WT) animals. This favorable outcome stemmed from an ameliorated inflammatory cytokine response to N. meningitidis in C5ar1\(^{-/-}\) mice in both in vivo and ex vivo whole-blood infections. In addition, inhibition of C5aR1 signaling without interference with the complement bactericidal activity reduced the inflammatory response also in human whole blood. Enticingly, pharmacologic C5aR1 blockade enhanced mouse survival and lowered meningococcal burden even when the treatment was administered after sepsis induction. Together, our findings demonstrate that C5aR1 drives the pathophysiology associated with meningococcal sepsis and provides a promising target for adjunctive therapy. Importance: The devastating consequences of N. meningitidis sepsis arise due to the rapidly arising and self-propagating inflammatory response that mobilizes antibacterial defenses but also drives the immunopathology associated with meningococcemia. The complement cascade provides innate broad-spectrum protection against infection by directly damaging the envelope of pathogenic microbes through the membrane attack complex and triggers an inflammatory response via the C5a peptide and its receptor C5aR1 aimed at mobilizing cellular effectors of immunity. Here, we consider the potential of separating the bactericidal activities of the complement cascade from its immune activating function to improve outcome of N. meningitidis sepsis. Our findings demonstrate that the specific genetic or pharmacological disruption of C5aR1 rapidly ameliorates disease by suppressing the pathogenic inflammatory response and, surprisingly, allows faster clearance of the bacterial infection. This outcome provides a clear demonstration of the therapeutic benefit of the use of C5aR1-specific inhibitors to improve the outcome of invasive meningococcal disease.}, language = {en} } @article{HofrichterMojaradDolletal.2018, author = {Hofrichter, Michaela A. H. and Mojarad, Majid and Doll, Julia and Grimm, Clemens and Eslahi, Atiye and Hosseini, Neda Sadat and Rajati, Mohsen and M{\"u}ller, Tobias and Dittrich, Marcus and Maroofian, Reza and Haaf, Thomas and Vona, Barbara}, title = {The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family}, series = {BMC Medical Genetics}, volume = {19}, journal = {BMC Medical Genetics}, number = {81}, doi = {10.1186/s12881-018-0598-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175755}, year = {2018}, abstract = {Background: Genetic heterogeneity and consanguineous marriages make recessive inherited hearing loss in Iran the second most common genetic disorder. Only two reported pathogenic variants (c.323G>C, p.Arg108Pro and c.419A>G, p.Tyr140Cys) in the S1PR2 gene have previously been linked to autosomal recessive hearing loss (DFNB68) in two Pakistani families. We describe a segregating novel homozygous c.323G>A, p.Arg108Gln pathogenic variant in S1PR2 that was identified in four affected individuals from a consanguineous five generation Iranian family. Methods: Whole exome sequencing and bioinformatics analysis of 116 hearing loss-associated genes was performed in an affected individual from a five generation Iranian family. Segregation analysis and 3D protein modeling of the p.Arg108 exchange was performed. Results: The two Pakistani families previously identified with S1PR2 pathogenic variants presented profound hearing loss that is also observed in the affected Iranian individuals described in the current study. Interestingly, we confirmed mixed hearing loss in one affected individual. 3D protein modeling suggests that the p.Arg108 position plays a key role in ligand receptor interaction, which is disturbed by the p.Arg108Gln change. Conclusion: In summary, we report the third overall mutation in S1PR2 and the first report outside the Pakistani population. Furthermore, we describe a novel variant that causes an amino acid exchange (p.Arg108Gln) in the same amino acid residue as one of the previously reported Pakistani families (p.Arg108Pro). This finding emphasizes the importance of the p.Arg108 amino acid in normal hearing and confirms and consolidates the role of S1PR2 in autosomal recessive hearing loss.}, language = {en} } @article{GilbertHeintelJakubietzetal.2018, author = {Gilbert, F. and Heintel, T. M. and Jakubietz, M. G. and K{\"o}stler, H. and Sebald, C. and Meffert, R. H. and Weng, A. M.}, title = {Quantitative MRI comparison of multifidus muscle degeneration in thoracolumbar fractures treated with open and minimally invasive approach}, series = {BMC Musculoskeletal Disorders}, volume = {19}, journal = {BMC Musculoskeletal Disorders}, number = {75}, doi = {10.1186/s12891-018-2001-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175742}, year = {2018}, abstract = {Background: Minimally invasive pedicle screw fixation has less approach-related morbidity than open screw placement and is allegedly less traumatizing on paravertebral muscles, as there is no requirement to mobilize and retract the adjacent muscle portion. The approach-related long-term effects to the morphology of the paravertebral muscles are unknown. The purpose of this study was to compare the long-term amount of fatty degeneration of the multifidus muscle in patients treated with a classical open or a minimally invasive approach. Methods: Fourteen Patients meeting inclusion criteria were selected. In all patients a singular fracture of the thoracolumbar spine with a two-level posterior instrumentation was treated, either using an open approach or a minimally invasive approach. All patients underwent quantitative MRI spectroscopy for quantification of the fatty degeneration in the multifidus muscle as a long-term proof for muscle loss after minimum 4-year follow-up. Clinical outcome was assessed using Oswestry Low Back Pain Disability Questionnaire, SF-36 and VA-scale for pain. Results: The minimally invasive approach group failed to show less muscle degeneration in comparison to the open group. Total amount of fatty degeneration was 14.22\% in the MIS group and 12.60\% in the open group (p = 0.64). In accordance to MRI quantitative results there was no difference in the clinical outcome after a mean follow up of 5.9 years (±1.8). Conclusion: As short-term advantages of minimal invasive screw placement have been widely demonstrated, no advantage of the MIS, displaying a significant difference in the amount of fatty degeneration and resulting in a better clinical outcome could be found. Besides the well-known short-term advantage of minimally invasive pedicle screw placement, a long-term advantage, such as less muscle degeneration and thus superior clinical results, compared to the open approach could not be shown.}, language = {en} } @article{StrahlGerlichAlpersetal.2018, author = {Strahl, Andr{\´e} and Gerlich, Christian and Alpers, Georg W. and Ehrmann, Katja and Gehrke, J{\"o}rg and M{\"u}ller-Garnn, Annette and Vogel, Heiner}, title = {Development and evaluation of a standardized peer-training in the context of peer review for quality assurance in work capacity evaluation}, series = {BMC Medical Education}, volume = {18}, journal = {BMC Medical Education}, number = {135}, doi = {10.1186/s12909-018-1233-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175738}, year = {2018}, abstract = {Background: The German quality assurance programme for evaluating work capacity is based on peer review that evaluates the quality of medical experts' reports. Low reliability is thought to be due to systematic differences among peers. For this purpose, we developed a curriculum for a standardized peer-training (SPT). This study investigates, whether the SPT increases the inter-rater reliability of social medical physicians participating in a cross-institutional peer review. Methods: Forty physicians from 16 regional German Pension Insurances were subjected to SPT. The three-day training course consist of nine educational objectives recorded in a training manual. The SPT is split into a basic module providing basic information about the peer review and an advanced module for small groups of up to 12 peers training peer review using medical reports. Feasibility was tested by assessing selection, comprehensibility and subjective use of contents delivered, the trainers' delivery and design of training materials. The effectiveness of SPT was determined by evaluating peer concordance using three anonymised medical reports assessed by each peer. Percentage agreement and Fleiss' kappa (κ\(_m\)) were calculated. Concordance was compared with review results from a previous unstructured, non-standardized peer-training programme (control condition) performed by 19 peers from 12 German Pension Insurances departments. The control condition focused exclusively on the application of peer review in small groups. No specifically training materials, methods and trainer instructions were used. Results: Peer-training was shown to be feasible. The level of subjective confidence in handling the peer review instrument varied between 70 and 90\%. Average percentage agreement for the main outcome criterion was 60.2\%, resulting in a κ\(_m\) of 0.39. By comparison, the average percentage concordance was 40.2\% and the κ\(_m\) was 0.12 for the control condition. Conclusion: Concordance with the main criterion was relevant but not significant (p = 0.2) higher for SPT than for the control condition. Fleiss' kappa coefficient showed that peer concordance was higher for SPT than randomly expected. Nevertheless, a score of 0.39 for the main criterion indicated only fair inter-rater reliability, considerably lower than the conventional standard of 0.7 for adequate reliability.}, language = {en} } @article{UsmanReimannLiedletal.2018, author = {Usman, Muhammad and Reimann, Thomas and Liedl, Rudolf and Abbas, Azhar and Conrad, Christopher and Saleem, Shoaib}, title = {Inverse parametrization of a regional groundwater flow model with the aid of modelling and GIS: test and application of different approaches}, series = {ISPRS International Journal of Geo-Information}, volume = {7}, journal = {ISPRS International Journal of Geo-Information}, number = {1}, doi = {10.3390/ijgi7010022}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175721}, pages = {22}, year = {2018}, abstract = {The use of inverse methods allow efficient model calibration. This study employs PEST to calibrate a large catchment scale transient flow model. Results are demonstrated by comparing manually calibrated approaches with the automated approach. An advanced Tikhonov regularization algorithm was employed for carrying out the automated pilot point (PP) method. The results indicate that automated PP is more flexible and robust as compared to other approaches. Different statistical indicators show that this method yields reliable calibration as values of coefficient of determination (R-2) range from 0.98 to 0.99, Nash Sutcliffe efficiency (ME) range from 0.964 to 0.976, and root mean square errors (RMSE) range from 1.68 m to 1.23 m, for manual and automated approaches, respectively. Validation results of automated PP show ME as 0.969 and RMSE as 1.31 m. The results of output sensitivity suggest that hydraulic conductivity is a more influential parameter. Considering the limitations of the current study, it is recommended to perform global sensitivity and linear uncertainty analysis for the better estimation of the modelling results.}, language = {en} }