TY - JOUR A1 - Rauert-Wunderlich, Hilka A1 - Berberich, Ingolf A1 - Rosenwald, Andreas A1 - Rudelius, Martina T1 - CD40L mediated alternative NF kappa B-signaling induces resistance to BCR-inhibitors in patients with mantle cell lymphoma JF - Cell Death & Disease N2 - Drug resistance is a significant obstacle in cancer treatment and therefore a frequent subject of research. Developed or primary resistance limits the treatment success of inhibitors of the B cell receptor (BCR) pathway in mantle cell lymphoma (MCL) patients. Recent research has highlighted the role of the nuclear factor-kappa B (NF kappa B) pathway in the context of resistance to BCR inhibitors in MCL. In this study, we analyzed the dependency of MCL cell lines on NF kappa B signaling and illustrated the ability of CD40L to activate the alternative NF kappa B pathway in MCL. This activation leads to independency of classical NF kappa B signaling and results in resistance to BCR inhibitors. Therefore, ligands (such as CD40L) and their activation of the alternative NF kappa B pathway have a major impact on the drug response in MCL. Furthermore, this study indicates a protective role for cells expressing specific ligands as microenvironmental niches for MCL cells and underlines the significance of therapeutically targeting alternative NF kappa B signaling in MCL. KW - Bruton Tyrosine Kinase KW - Tumor Microenvironment KW - Targeted Therapies KW - Ibrutinib KW - Pathway KW - Malignancies KW - Activation KW - Ligand KW - Proliferation KW - PCI-32765 Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225027 IS - 9 ER - TY - JOUR A1 - Scheer, Ulrich T1 - Boveri's research at the Zoological Station Naples: Rediscovery of his original microscope slides at the University of Würzburg JF - Marine Genomics N2 - Eric Davidson once wrote about Theodor Boveri: "From his own researches, and perhaps most important, his generalized interpretations, derive the paradigms that underlie modern inquiries into the genomic basis of embryogenesis" (Davidson, 1985). As luck would have it, the "primary data" of Boveri's experimental work, namely the microscope slides prepared by him and his wife Marcella during several stays at the Zoological Station in Naples (1901/02, 1911/12 and 1914), have survived at the University of Wurzburg. More than 600 slides exist and despite their age they are in a surprisingly good condition. The slides are labelled and dated in Boveri's handwriting and thus can be assigned to his published experimental work on sea urchin development. The results allowed Boveri to unravel the role of the cell nucleus and its chromosomes in development and inheritance. Here, I present an overview of the slides in the context of Boveri's work along with photographic images of selected specimens taken from the original slides. It is planned to examine the slides in more detail, take high-resolution focal image series of significant specimens and make them online available. KW - Sea urchin development KW - Polyspermy KW - Multipolar mitosis KW - Aneuploidy KW - Merogone experiments KW - Science history Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228453 VL - 40 ER - TY - JOUR A1 - Rostás, Michael A1 - Bollmann, Felix A1 - Saville, David A1 - Riedel, Michael T1 - Ants contribute to pollination but not to reproduction in a rare calcareous grassland forb JF - PeerJ N2 - The number of plants pollinated by ants is surprisingly low given the abundance of ants and the fact that they are common visitors of angiosperms. Generally ants are considered as nectar robbers that do not provide pollination service. We studied the pollination system of the endangered dry grassland forb Euphorbia seguieriana and found two ant species to be the most frequent visitors of its flowers. Workers of Formica cunicularia carried five times more pollen than smaller Tapinoma erraticum individuals, but significantly more viable pollen was recovered from the latter. Overall, the viability of pollen on ant cuticles was significantly lower (p < 0.001)-presumably an antibiotic effect of the metapleural gland secretion. A marking experiment suggested that ants were unlikely to facilitate outcrossing as workers repeatedly returned to the same individual plant. In open pollinated plants and when access was given exclusively to flying insects, fruit set was nearly 100%. In plants visited by ants only, roughly one third of flowers set fruit, and almost none set fruit when all insects were excluded. The germination rate of seeds from flowers pollinated by flying insects was 31 +/- 7% in contrast to 1 +/- 1% resulting from ant pollination. We conclude that inbreeding depression may be responsible for the very low germination rate in ant pollinated flowers and that ants, although the most frequent visitors, play a negligible or even deleterious role in the reproduction of E. seguieriana. Our study reiterates the need to investigate plant fitness effects beyond seed set in order to confirm ant-plant mutualisms. KW - Ants KW - Breeding system KW - Geitonogamy KW - Germination KW - Inbreeding depression KW - Metapleural gland KW - Siberian spurge KW - Foraging behaviour KW - Pollen KW - Ecology KW - Entomology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227053 VL - 6 ER - TY - JOUR A1 - Rieger, C. T. A1 - Liss, B. A1 - Mellinghoff, S. A1 - Buchheidt, D. A1 - Cornely, O. A. A1 - Egerer, G. A1 - Heinz, W. J. A1 - Hentrich, M. A1 - Maschmeyer, G. A1 - Mayer, K. A1 - Sandherr, M. A1 - Silling, G. A1 - Ullmann, A. A1 - Vehreschild, M. J. G. T. A1 - von Lilienfeld-Toal, M. A1 - Wolf, H. H. A1 - Lehners, N. T1 - Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) JF - Annals of Oncology N2 - Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria. KW - infection KW - anti-infective vaccination KW - cancer KW - immunosuppression KW - autologous stem cell transplantation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226196 VL - 29 IS - 6 ER - TY - JOUR A1 - Schihada, Hannes A1 - Vandenabeele, Sylvie A1 - Zabel, Ulrike A1 - Frank, Monika A1 - Lohse, Martin J. A1 - Maiellaro, Isabella T1 - A universal bioluminescence resonance energy transfer sensor design enables high-sensitivity screening of GPCR activation dynamics JF - Communications Biology N2 - G-protein-coupled receptors (GPCRs) represent one of the most important classes of drug targets. The discovery of new GCPR therapeutics would greatly benefit from the development of a generalizable high-throughput assay to directly monitor their activation or de-activation. Here we screened a variety of labels inserted into the third intracellular loop and the C-terminus of the alpha(2 Lambda)-adrenergic receptor and used fluorescence (FRET) and bioluminescence resonance energy transfer (BRET) to monitor ligand-binding and activation dynamics. We then developed a universal intramolecular BRET receptor sensor design to quantify efficacy and potency of GPCR ligands in intact cells and real time. We demonstrate the transferability of the sensor design by cloning beta(2)-adrenergic and PTH1-receptor BRET sensors and monitored their efficacy and potency. For all biosensors, the Z factors were well above 0.5 showing the suitability of such design for microtiter plate assays. This technology will aid the identification of novel types of GPCR ligands. KW - Fluorescence resonance energy transfer KW - G protein-coupled receptors KW - High-throughput screening Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228592 VL - 1 IS - 105 ER - TY - JOUR A1 - Rogowski-Lehmann, Natalie A1 - Geroula, Aikaterini A1 - Prejbisz, Aleksander A1 - Timmers, Henri J. L. M. A1 - Megerle, Felix A1 - Robledo, Mercedes A1 - Fassnacht, Martin A1 - Fliedner, Stephanie M. J. A1 - Reincke, Martin A1 - Stell, Anthony A1 - Januszewicz, Andrzej A1 - Lenders, Jacques W. M. A1 - Eisenhofer, Graeme A1 - Beuschlein, Felix T1 - Missed clinical clues in patients with pheochromocytoma/paraganglioma discovered by imaging JF - Endocrine Connections N2 - Background: Pheochromocytomas and paragangliomas (PPGLs) are rare but potentially harmful tumors that can vary in their clinical presentation. Tumors may be found due to signs and symptoms, as part of a hereditary syndrome or following an imaging procedure. Objective: To investigate potential differences in clinical presentation between PPGLs discovered by imaging (iPPGLs), symptomatic cases (sPPGLs) and those diagnosed during follow-up because of earlier disease/known hereditary mutations (fPPGL). Design: Prospective study protocol, which has enrolled patients from six European centers with confirmed PPGLs. Data were analyzed from 235 patients (37 iPPGLs, 36 sPPGLs, 27% fPPGLs) and compared for tumor volume, biochemical profile, mutation status, presence of metastases and self-reported symptoms. iPPGL patients were diagnosed at a significantly higher age than fPPGLs (P<0.001), found to have larger tumors (P=0.003) and higher metanephrine and normetanephrine levels at diagnosis (P=0.021). Significantly lower than in sPPGL, there was a relevant number of self-reported symptoms in iPPGL (2.9 vs 4.3 symptoms, P< 0.001). In 16.2% of iPPGL, mutations in susceptibility genes were detected, although this proportion was lower than that in fPPGL (60.9%) and sPPGL (21.5%). Patients with PPGLs detected by imaging were older, have higher tumor volume and more excessive hormonal secretion in comparison to those found as part of a surveillance program. Presence of typical symptoms indicates that in a relevant proportion of those patients, the PPGL diagnosis had been delayed. Precis: Pheochromocytoma/paraganglioma discovered by imaging are often symptomatic and carry a significant proportion of germline mutations in susceptibility genes. KW - pheochromocytoma KW - paraganglioma KW - imaging KW - signs and symptoms KW - prospective KW - Biochemical-Diagnosis KW - Plasma KW - MASS KW - Normetanephrine KW - Metanephrine KW - Paraganglioma KW - Society KW - Utility Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226481 VL - 7 IS - 11 ER - TY - JOUR A1 - Refardt, Julie A1 - Sailer, Clara Odilia A1 - Winzeler, Bettina A1 - Betz, Matthias Johannes A1 - Chifu, Irina A1 - Schnyder, Ingeborg A1 - Fassnacht, Martin A1 - Fenske, Wiebke A1 - Christ-Crain, Mirjam T1 - FGF-21 levels in polyuria-polydipsia syndrome JF - Endocrine Connections N2 - The pathomechanism of primary polydipsia is poorly understood. Recent animal data reported a connection between fibroblast growth factor 21 (FGF-21) and elevated fluid intake independently of hormonal control by the hormone arginine-vasopressin (AVP) and osmotic stimulation. We therefore compared circulating FGF-21 levels in patients with primary polydipsia to patients with AVP deficiency (central diabetes insipidus) and healthy volunteers. In this prospective cohort study, we analyzed FGF-21 levels of 20 patients with primary polydipsia, 20 patients with central diabetes insipidus and 20 healthy volunteers before and after stimulation with hypertonic saline infusion targeting a plasma sodium level >= 150 mmol/L. The primary outcome was the difference in FGF-21 levels between the three groups. Baseline characteristics were similar between the groups except for patients with central diabetes insipidus being heavier. There was no difference in baseline FGF-21 levels between patients with primary polydipsia and healthy volunteers (122 pg/mL (52,277) vs 193 pg/mL (48,301), but higher levels in patients with central diabetes insipidus were observed (306 pg/mL (114,484); P=0.037). However, this was not confirmed in a multivariate linear regression analysis after adjusting for age, sex, BMI and smoking status. Osmotic stimulation did not affect FGF-21 levels in either group (difference to baseline: primary polydipsia -23 pg/mL (-43, 22); central diabetes insipidus 17 pg/mL (-76, 88); healthy volunteers -6 pg/mL (-68, 22); P=0.45). To conclude, FGF-21 levels are not increased in patients with primary polydipsia as compared to central diabetes insipidus or healthy volunteers. FGF-21 therefore does not seem to be causal of elevated fluid intake in these patients. KW - FGF21 KW - diabetes insipidus KW - primary polydipsia KW - osmotic stimulation KW - copeptin KW - Fibroblast Growth Factor-21 KW - Klotho-related molecules KW - Copeptin KW - Diagnosis KW - PF-05231023 KW - Resistance KW - Men Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225085 VL - 7 IS - 12 ER - TY - JOUR A1 - Greving, Sven A1 - Richter, Tobias T1 - Examining the testing effect in university teaching: retrievability and question format matter JF - Frontiers in Psychology N2 - Review of learned material is crucial for the learning process. One approach that promises to increase the effectiveness of reviewing during learning is to answer questions about the learning content rather than restudying the material (testing effect). This effect is well established in lab experiments. However, existing research in educational contexts has often combined testing with additional didactical measures that hampers the interpretation of testing effects. We aimed to examine the testing effect in its pure form by implementing a minimal intervention design in a university lecture (N = 92). The last 10 min of each lecture session were used for reviewing the lecture content by either answering short-answer questions, multiple-choice questions, or reading summarizing statements about core lecture content. Three unannounced criterial tests measured the retention of learning content at different times (1, 12, and 23 weeks after the last lecture). A positive testing effect emerged for short-answer questions that targeted information that participants could retrieve from memory. This effect was independent of the time of test. The results indicated no testing effect for multiple-choice testing. These results suggest that short-answer testing but not multiple-choice testing may benefit learning in higher education contexts. KW - testing effect KW - university teaching KW - retrieval practice KW - question format KW - educational psychology KW - net testing effect KW - desirable difficulties Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190802 SN - 1664-1078 VL - 9 ER - TY - JOUR A1 - Krause, Stefan A1 - Weber, Silvana T1 - Lift me up by looking down: social comparison effects of narratives JF - Frontiers in Psychology N2 - Stories are a powerful means to change recipients’ views on themselves by being transported into the story world and by identifying with story characters. Previous studies showed that recipients temporarily change in line with a story and its characters (assimilation). Conversely, assimilation might be less likely when recipients are less identified with story protagonists or less transported into a story by comparing themselves with a story character. This may lead to changes, which are opposite to a story and its characters (contrast). In two experiments, we manipulated transportation and experience taking via two written reviews (Experiment 1; N = 164) and by varying the perspective of the story’s narrator (Experiment 2; N = 79) of a short story about a negligent student. Recipients’ self-ratings in comparison to others, motives, and problem-solving behavior served as dependent variables. However, neither the review nor the perspective manipulation affected transportation or experience taking while reading the story. Against our expectations, highly transported recipients (in Study 1) and recipients with high experience taking (in Study 2) showed more persistency working on an anagram-solving task, even when controlling for trait conscientiousness. Our findings are critically discussed in light of previous research. KW - self KW - self-concept KW - transportation KW - identification KW - experience taking KW - narratives KW - social comparison Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190624 SN - 1664-1078 VL - 9 ER - TY - JOUR A1 - Fujiwara, Yuri A1 - Hermann-Luibl, Christiane A1 - Katsura, Maki A1 - Sekiguchi, Manabu A1 - Ida, Takanori A1 - Helfrich-Förster, Charlotte A1 - Yoshii, Taishi T1 - The CCHamide1 Neuropeptide Expressed in the Anterior Dorsal Neuron 1 Conveys a Circadian Signal to the Ventral Lateral Neurons in Drosophila melanogaster JF - Frontiers in Physiology N2 - The fruit fly Drosophila melanogaster possesses approximately 150 brain clock neurons that control circadian behavioral rhythms. Even though individual clock neurons have self-sustaining oscillators, they interact and synchronize with each other through a network. However, little is known regarding the factors responsible for these network interactions. In this study, we investigated the role of CCHamide1 (CCHa1), a neuropeptide expressed in the anterior dorsal neuron 1 (DN1a), in intercellular communication of the clock neurons. We observed that CCHa1 connects the DN1a clock neurons to the ventral lateral clock neurons (LNv) via the CCHa1 receptor, which is a homolog of the gastrin-releasing peptide receptor playing a role in circadian intercellular communications in mammals. CCHa1 knockout or knockdown flies have a generally low activity level with a special reduction of morning activity. In addition, they exhibit advanced morning activity under light-dark cycles and delayed activity under constant dark conditions, which correlates with an advance/delay of PAR domain Protein 1 (PDP1) oscillations in the small-LNv (s-LNv) neurons that control morning activity. The terminals of the s-LNv neurons show rather high levels of Pigment-dispersing factor (PDF) in the evening, when PDF is low in control flies, suggesting that the knockdown of CCHa1 leads to increased PDF release; PDF signals the other clock neurons and evidently increases the amplitude of their PDP1 cycling. A previous study showed that high-amplitude PDP1 cycling increases the siesta of the flies, and indeed, CCHa1 knockout or knockdown flies exhibit a longer siesta than control flies. The DN1a neurons are known to be receptive to PDF signaling from the s-LNv neurons; thus, our results suggest that the DN1a and s-LNv clock neurons are reciprocally coupled via the neuropeptides CCHa1 and PDF, and this interaction fine-tunes the timing of activity and sleep. KW - circadian clock KW - circadian rhythm KW - CCHamide1 KW - pacemaker neuron KW - neuropeptide KW - pigment-dispersing factor Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195940 SN - 1664-042X VL - 09 ER - TY - JOUR A1 - Beck, Katherina A1 - Hovhanyan, Anna A1 - Menegazzi, Pamela A1 - Helfrich-Förster, Charlotte A1 - Raabe, Thomas T1 - Drosophila RSK Influences the Pace of the Circadian Clock by Negative Regulation of Protein Kinase Shaggy Activity JF - Frontiers in Molecular Neuroscience N2 - Endogenous molecular circadian clocks drive daily rhythmic changes at the cellular, physiological, and behavioral level for adaptation to and anticipation of environmental signals. The core molecular system consists of autoregulatory feedback loops, where clock proteins inhibit their own transcription. A complex and not fully understood interplay of regulatory proteins influences activity, localization and stability of clock proteins to set the pace of the clock. This study focuses on the molecular function of Ribosomal S6 Kinase (RSK) in the Drosophila melanogaster circadian clock. Mutations in the human rsk2 gene cause Coffin–Lowry syndrome, which is associated with severe mental disabilities. Knock-out studies with Drosophila ortholog rsk uncovered functions in synaptic processes, axonal transport and adult behavior including associative learning and circadian activity. However, the molecular targets of RSK remain elusive. Our experiments provide evidence that RSK acts in the key pace maker neurons as a negative regulator of Shaggy (SGG) kinase activity, which in turn determines timely nuclear entry of the clock proteins Period and Timeless to close the negative feedback loop. Phosphorylation of serine 9 in SGG is mediated by the C-terminal kinase domain of RSK, which is in agreement with previous genetic studies of RSK in the circadian clock but argues against the prevailing view that only the N-terminal kinase domain of RSK proteins carries the effector function. Our data provide a mechanistic explanation how RSK influences the molecular clock and imply SGG S9 phosphorylation by RSK and other kinases as a convergence point for diverse cellular and external stimuli. KW - circadian clock KW - Period KW - Timeless KW - Shaggy kinase KW - RSK KW - Coffin–Lowry syndrome Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196034 SN - 1662-5099 VL - 11 IS - 122 ER - TY - JOUR A1 - Li, Cong A1 - Deng, Xiaobing A1 - Xie, Xiaowen A1 - Liu, Ying A1 - Friedmann Angeli, José Pedro A1 - Lai, Luhua T1 - Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy JF - Frontiers in Pharmacology N2 - The anti-oxidative enzyme, glutathione peroxidase 4 (GPX4), helps to promote inflammation resolution by eliminating oxidative species produced by the arachidonic acid (AA) metabolic network. Up-regulating its activity has been proposed as a promising strategy for inflammation intervention. In the present study, we aimed to study the effect of GPX4 activator on the AA metabolic network and inflammation related pathways. Using combined computational and experimental screen, we identified a novel compound that can activate the enzyme activity of GPX4 by more than two folds. We further assessed its potential in a series of cellular assays where GPX4 was demonstrated to play a regulatory role. We are able to show that GPX4 activation suppressed inflammatory conditions such as oxidation of AA and NF-κB pathway activation. We further demonstrated that this GPX4 activator can decrease the intracellular ROS level and suppress ferroptosis. Our study suggests that GPX4 activators can be developed as anti-inflammatory or cyto-protective agent in lipid-peroxidation-mediated diseases. KW - arachidonic acid metabolic network KW - GPX4 KW - enzyme activator KW - allosterism KW - drug discovery KW - anti-inflammatory KW - ferroptosis Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195985 SN - 1663-9812 VL - 9 IS - 1120 ER - TY - JOUR A1 - Schaefer, Natascha A1 - Zheng, Fang A1 - van Brederode, Johannes A1 - Berger, Alexandra A1 - Leacock, Sophie A1 - Hirata, Hiromi A1 - Paige, Christopher J. A1 - Harvey, Robert J. A1 - Alzheimer, Christian A1 - Villmann, Carmen T1 - Functional Consequences of the Postnatal Switch From Neonatal to Mutant Adult Glycine Receptor α1 Subunits in the Shaky Mouse Model of Startle Disease JF - Frontiers in Molecular Neuroscience N2 - Mutations in GlyR α1 or β subunit genes in humans and rodents lead to severe startle disease characterized by rigidity, massive stiffness and excessive startle responses upon unexpected tactile or acoustic stimuli. The recently characterized startle disease mouse mutant shaky carries a missense mutation (Q177K) in the β8-β9 loop within the large extracellular N-terminal domain of the GlyR α1 subunit. This results in a disrupted hydrogen bond network around K177 and faster GlyR decay times. Symptoms in mice start at postnatal day 14 and increase until premature death of homozygous shaky mice around 4–6 weeks after birth. Here we investigate the in vivo functional effects of the Q177K mutation using behavioral analysis coupled to protein biochemistry and functional assays. Western blot analysis revealed GlyR α1 subunit expression in wild-type and shaky animals around postnatal day 7, a week before symptoms in mutant mice become obvious. Before 2 weeks of age, homozygous shaky mice appeared healthy and showed no changes in body weight. However, analysis of gait and hind-limb clasping revealed that motor coordination was already impaired. Motor coordination and the activity pattern at P28 improved significantly upon diazepam treatment, a pharmacotherapy used in human startle disease. To investigate whether functional deficits in glycinergic neurotransmission are present prior to phenotypic onset, we performed whole-cell recordings from hypoglossal motoneurons (HMs) in brain stem slices from wild-type and shaky mice at different postnatal stages. Shaky homozygotes showed a decline in mIPSC amplitude and frequency at P9-P13, progressing to significant reductions in mIPSC amplitude and decay time at P18-24 compared to wild-type littermates. Extrasynaptic GlyRs recorded by bath-application of glycine also revealed reduced current amplitudes in shaky mice compared to wild-type neurons, suggesting that presynaptic GlyR function is also impaired. Thus, a distinct, but behaviorally ineffective impairment of glycinergic synapses precedes the symptoms onset in shaky mice. These findings extend our current knowledge on startle disease in the shaky mouse model in that they demonstrate how the progression of GlyR dysfunction causes, with a delay of about 1 week, the appearance of disease symptoms. KW - glycine receptor KW - startle disease KW - β8-β9 loop KW - mouse model KW - fast decay Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196056 SN - 1662-5099 VL - 11 IS - 167 ER - TY - JOUR A1 - Bahmer, Andreas A1 - Gupta, Daya Shankar T1 - Role of Oscillations in Auditory Temporal Processing: A General Model for Temporal Processing of Sensory Information in the Brain? JF - Frontiers in Neuroscience N2 - We review the role of oscillations in the brain and in the auditory system showing that the ability of humans to distinguish changes in pitch can be explained as a precise analysis of temporal information in auditory signals by neural oscillations. The connections between auditory brain stem chopper neurons construct neural oscillators, which discharge spikes at various constant intervals that are integer multiples of 0.4 ms, contributing to the temporal processing of auditory cochlear output. This is subsequently spatially mapped in the inferior colliculus. Electrophysiological measurements of auditory chopper neurons in different species show oscillations with periods which are integer multiples of 0.4 ms. The constant intervals of 0.4 ms can be attributed to the smallest synaptic delay between interconnected simulated chopper neurons. We also note the patterns of similarities between microcircuits in the brain stem and other parts of the brain (e.g., the pallidum, reticular formation, locus coeruleus, oculomotor nuclei, limbic system, amygdala, hippocampus, basal ganglia and substantia nigra), dedicated to the processing of temporal information. Similarities in microcircuits across the brain reflect the importance of one of the key mechanisms in the information processing in the brain, namely the temporal coupling of different neural events via coincidence detection. KW - canonical microcircuits KW - cochlear nucleus KW - locus coerulus KW - limbic system KW - amygdala KW - hippocampus KW - basal ganglia KW - substantia nigra Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196087 SN - 1662-453X VL - 12 IS - 793 ER - TY - JOUR A1 - Gromer, Daniel A1 - Madeira, Octávia A1 - Gast, Philipp A1 - Nehfischer, Markus A1 - Jost, Michael A1 - Müller, Mathias A1 - Mühlberger, Andreas A1 - Pauli, Paul T1 - Height Simulation in a Virtual Reality CAVE System: Validity of Fear Responses and Effects of an Immersion Manipulation JF - Frontiers in Human Neuroscience N2 - Acrophobia is characterized by intense fear in height situations. Virtual reality (VR) can be used to trigger such phobic fear, and VR exposure therapy (VRET) has proven effective for treatment of phobias, although it remains important to further elucidate factors that modulate and mediate the fear responses triggered in VR. The present study assessed verbal and behavioral fear responses triggered by a height simulation in a 5-sided cave automatic virtual environment (CAVE) with visual and acoustic simulation and further investigated how fear responses are modulated by immersion, i.e., an additional wind simulation, and presence, i.e., the feeling to be present in the VE. Results revealed a high validity for the CAVE and VE in provoking height related self-reported fear and avoidance behavior in accordance with a trait measure of acrophobic fear. Increasing immersion significantly increased fear responses in high height anxious (HHA) participants, but did not affect presence. Nevertheless, presence was found to be an important predictor of fear responses. We conclude that a CAVE system can be used to elicit valid fear responses, which might be further enhanced by immersion manipulations independent from presence. These results may help to improve VRET efficacy and its transfer to real situations. KW - anxiety KW - fear behavior KW - virtual reality KW - presence KW - immersion KW - acrophobia Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196113 SN - 1662-5161 VL - 12 IS - 372 ER - TY - JOUR A1 - Ventura-Bort, Carlos A1 - Wirkner, Janine A1 - Genheimer, Hannah A1 - Wendt, Julia A1 - Hamm, Alfons O. A1 - Weymar, Mathias T1 - Effects of Transcutaneous Vagus Nerve Stimulation (tVNS) on the P300 and Alpha-Amylase Level: A Pilot Study JF - Frontiers in Human Neuroscience N2 - Recent research suggests that the P3b may be closely related to the activation of the locus coeruleus-norepinephrine (LC-NE) system. To further study the potential association, we applied a novel technique, the non-invasive transcutaneous vagus nerve stimulation (tVNS), which is speculated to increase noradrenaline levels. Using a within-subject cross-over design, 20 healthy participants received continuous tVNS and sham stimulation on two consecutive days (stimulation counterbalanced across participants) while performing a visual oddball task. During stimulation, oval non-targets (standard), normal-head (easy) and rotated-head (difficult) targets, as well as novel stimuli (scenes) were presented. As an indirect marker of noradrenergic activation we also collected salivary alpha-amylase (sAA) before and after stimulation. Results showed larger P3b amplitudes for target, relative to standard stimuli, irrespective of stimulation condition. Exploratory post hoc analyses, however, revealed that, in comparison to standard stimuli, easy (but not difficult) targets produced larger P3b (but not P3a) amplitudes during active tVNS, compared to sham stimulation. For sAA levels, although main analyses did not show differential effects of stimulation, direct testing revealed that tVNS (but not sham stimulation) increased sAA levels after stimulation. Additionally, larger differences between tVNS and sham stimulation in P3b magnitudes for easy targets were associated with larger increase in sAA levels after tVNS, but not after sham stimulation. Despite preliminary evidence for a modulatory influence of tVNS on the P3b, which may be partly mediated by activation of the noradrenergic system, additional research in this field is clearly warranted. Future studies need to clarify whether tVNS also facilitates other processes, such as learning and memory, and whether tVNS can be used as therapeutic tool. KW - EEG KW - P300 KW - tVNS KW - norepinephrine KW - locus coeruleus KW - salivary alpha-amylase Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196129 SN - 1662-5161 VL - 12 IS - 202 ER - TY - JOUR A1 - Mahyera, Alexis S. A1 - Schneider, Tamara A1 - Halliger-Keller, Birgit A1 - Schrooten, Katja A1 - Hörner, Eva-Maria A1 - Rost, Simone A1 - Kress, Wolfram T1 - Distribution and Structure of DM2 Repeat Tract Alleles in the German Population JF - Frontiers in Neurology N2 - Autosomal dominant inherited Myotonic dystrophy type 1 and 2 (DM1 and DM2) are the most frequent muscle dystrophies in the European population and are caused by repeat expansion mutations. For Germany cumulative empiric evidence suggests an estimated prevalence of DM2 of roughly 9 in 100,000, therefore being as prevalent as DM1. In DM2, a (CCTG)n repeat tract located in the first intron of the CNBP gene is expanded. The CCTG repeat tract is part of a complex repeat structure comprising not only CCTG tetraplets but also repeated TG dinucleotides and TCTG tetraplet elements as well as NCTG interruptions. Here, we provide the distribution of normal sized alleles in the German population, which was found to be highly similar to the Slovak population. Sequencing of 34 unexpanded healthy range alleles in DM2 positive patients (heterozygous for a full expansion) revealed that the CCTG repeat tract is usually interrupted by at least three tetraplets which according to current opinion is supposed to render it stable against expansion. Interestingly, only the largest analyzed normal allele had 23 uninterrupted CCTGs and consequently could represent an instable early premutation allele. In our diagnostic history of DM2 cases, a total of 18 premutations were detected in 16 independent cases. Here, we describe two premutation families, one with an expansion from a premutation allele and the other with a contraction of a full expansion down to a premutation allele. Our diagnostic results support the general assumption that the premutation range of unstable CCTG stretches lies obviously between 25 and 75 CCTGs. However, the clinical significance of premutation alleles is still unclear. In the light of the two described families we suggest incomplete penetrance. Thus, as it was proposed for other repeat expansion diseases (e.g., Huntington's disease), a fluid transition of penetrance is more likely rather than a clear cut CCTG number threshold. KW - DM2 KW - intergenerational contraction KW - expansion KW - premutation KW - penetrance KW - prevalence Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196252 SN - 1664-2295 VL - 9 IS - 463 ER - TY - JOUR A1 - Prusty, Bhupesh K. A1 - Chowdhury, Suvagata R. A1 - Gulve, Nitish A1 - Rudel, Thomas T1 - Peptidase Inhibitor 15 (PI15) Regulates Chlamydial CPAF Activity JF - Frontiers in Cellular and Infection Microbiology N2 - Obligate intracellular pathogenic Chlamydia trachomatis express several serine proteases whose roles in chlamydial development and pathogenicity are not completely understood. The chlamydial protease CPAF is expressed during the replicative phase of the chlamydial developmental cycle and is secreted into the lumen of the Chlamydia-containing vacuole called inclusion. How the secreted protease is activated in the inclusion lumen is currently not fully understood. We have identified human serine peptidase inhibitor PI15 as a potential host factor involved in the regulation of CPAF activation. Silencing expression as well as over expression of PI15 affected normal development of Chlamydia. PI15 was transported into the chlamydial inclusion lumen where it co-localized with CPAF aggregates. We show that PI15 binds to the CPAF zymogen and potentially induces CPAF protease activity at low concentrations. However, at high concentrations PI15 inhibits CPAF activity possibly by blocking its protease domain. Our findings shed light on a new aspect of chlamydial host co-evolution which involves the recruitment of host cell proteins into the inclusion to control the activation of bacterial proteases like CPAF that are important for the normal development of Chlamydia. KW - chlamydia KW - CPAF activation KW - peptidase inhibitor PI15 KW - chlamydial inclusion KW - chlamydia serine proteases Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196918 SN - 2235-2988 VL - 8 IS - 183 ER - TY - JOUR A1 - Anelli, Viviana A1 - Ordas, Anita A1 - Kneitz, Susanne A1 - Sagredo, Leonel Munoz A1 - Gourain, Victor A1 - Schartl, Manfred A1 - Meijer, Annemarie H. A1 - Mione, Marina T1 - Ras-Induced miR-146a and 193a Target Jmjd6 to Regulate Melanoma Progression JF - Frontiers in Genetics N2 - Ras genes are among the most commonly mutated genes in human cancer; yet our understanding of their oncogenic activity at the molecular mechanistic level is incomplete. To identify downstream events that mediate ras-induced cellular transformation in vivo, we analyzed global microRNA expression in three different models of Ras-induction and tumor formation in zebrafish. Six microRNAs were found increased in Ras-induced melanoma, glioma and in an inducible model of ubiquitous Ras expression. The upregulation of the microRNAs depended on the activation of the ERK and AKT pathways and to a lesser extent, on mTOR signaling. Two Ras-induced microRNAs (miR-146a and 193a) target Jmjd6, inducing downregulation of its mRNA and protein levels at the onset of Ras expression during melanoma development. However, at later stages of melanoma progression, jmjd6 levels were found elevated. The dynamic of Jmjd6 levels during progression of melanoma in the zebrafish model suggests that upregulation of the microRNAs targeting Jmjd6 may be part of an anti-cancer response. Indeed, triple transgenic fish engineered to express a microRNA-resistant Jmjd6 from the onset of melanoma have increased tumor burden, higher infiltration of leukocytes and shorter melanoma-free survival. Increased JMJD6 expression is found in several human cancers, including melanoma, suggesting that the up-regulation of Jmjd6 is a critical event in tumor progression. The following link has been created to allow review of record GSE37015: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jjcrbiuicyyqgpc&acc=GSE37015. KW - zebrafish KW - cancer models KW - microRNA KW - Jmjd6 KW - ras KW - melanoma KW - miR-146a KW - miR-193a Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196963 SN - 1664-8021 VL - 9 IS - 675 ER - TY - JOUR A1 - Dasari, Prasad A1 - Shopova, Iordana A. A1 - Stroe, Maria A1 - Wartenberg, Dirk A1 - Martin-Dahse, Hans A1 - Beyersdorf, Niklas A1 - Hortschansky, Peter A1 - Dietrich, Stefanie A1 - Cseresnyés, Zoltán A1 - Figge, Marc Thilo A1 - Westermann, Martin A1 - Skerka, Christine A1 - Brakhage, Axel A. A1 - Zipfel, Peter F. T1 - Aspf2 From Aspergillus fumigatus Recruits Human Immune Regulators for Immune Evasion and Cell Damage JF - Frontiers in Immunology N2 - The opportunistic fungal pathogen Aspergillus fumigatus can cause life-threatening infections, particularly in immunocompromised patients. Most pathogenic microbes control host innate immune responses at the earliest time, already before infiltrating host immune cells arrive at the site of infection. Here, we identify Aspf2 as the first A. fumigatus Factor H-binding protein. Aspf2 recruits several human plasma regulators, Factor H, factor-H-like protein 1 (FHL-1), FHR1, and plasminogen. Factor H contacts Aspf2 via two regions located in SCRs6–7 and SCR20. FHL-1 binds via SCRs6–7, and FHR1 via SCRs3–5. Factor H and FHL-1 attached to Aspf2-maintained cofactor activity and assisted in C3b inactivation. A Δaspf2 knockout strain was generated which bound Factor H with 28% and FHL-1 with 42% lower intensity. In agreement with less immune regulator acquisition, when challenged with complement-active normal human serum, Δaspf2 conidia had substantially more C3b (>57%) deposited on their surface. Consequently, Δaspf2 conidia were more efficiently phagocytosed (>20%) and killed (44%) by human neutrophils as wild-type conidia. Furthermore, Aspf2 recruited human plasminogen and, when activated by tissue-type plasminogen activator, newly generated plasmin cleaved the chromogenic substrate S2251 and degraded fibrinogen. Furthermore, plasmin attached to conidia damaged human lung epithelial cells, induced cell retraction, and caused matrix exposure. Thus, Aspf2 is a central immune evasion protein and plasminogen ligand of A. fumigatus. By blocking host innate immune attack and by disrupting human lung epithelial cell layers, Aspf2 assists in early steps of fungal infection and likely allows tissue penetration. KW - complement KW - blocking opsonization KW - phagocytosis KW - acquisition of host regulators KW - immune evasion Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197013 SN - 1664-3224 VL - 9 IS - 1635 ER - TY - JOUR A1 - Rhodes, David A. A1 - Chen, Hung-Chang A1 - Williamson, James C. A1 - Hill, Alfred A1 - Yuan, Jack A1 - Smith, Sam A1 - Rhodes, Harriet A1 - Trowsdale, John A1 - Lehner, Paul J. A1 - Herrmann, Thomas A1 - Eberl, Matthias T1 - Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters JF - Frontiers in Immunology N2 - Activation of human Vγ9/Vδ2 T cells by “phosphoantigens” (pAg), the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach these problems, we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 T cell receptor (TCR) transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules, such as periplakin or RhoB, did not account for the functional variation between HeLa-L and HeLa-M cells. Instead, the data implicate a checkpoint controlling BTN3A1 stability and protein trafficking, acting at an early time point in its maturation. In addition, plasma membrane profiling was used to identify proteins upregulated in HMB-PP-treated HeLa-M. ABCG2, a member of the ATP-binding cassette (ABC) transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated with efficiency of T cell activation by cytokine secretion, although direct evidence of a functional role was not obtained by knockdown experiments. Our findings indicate a link between members of the ABC protein superfamily and the BTN3A-dependent activation of γδ T cells by endogenous and exogenous pAg. KW - butyrophilins KW - T cells KW - phosphoantigens KW - mevalonate pathway KW - ABCG2 KW - NRF2 Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197054 SN - 1664-3224 VL - 9 IS - 662 ER - TY - JOUR A1 - Pieger, Elisabeth A1 - Mengelkamp, Christoph A1 - Bannert, Maria T1 - Disfluency as a Desirable Difficulty — The Effects of Letter Deletion on Monitoring and Performance JF - Frontiers in Education N2 - Desirable difficulties initiate learning processes that foster performance. Such a desirable difficulty is generation, e.g., filling in deleted letters in a deleted letter text. Likewise, letter deletion is a manipulation of processing fluency: A deleted letter text is more difficult to process than an intact text. Disfluency theory also supposes that disfluency initiates analytic processes and thus, improves performance. However, performance is often not affected but, rather, monitoring is affected. The aim of this study is to propose a specification of the effects of disfluency as a desirable difficulty: We suppose that mentally filling in deleted letters activates analytic monitoring but not necessarily analytic cognitive processing and improved performance. Moreover, once activated, analytic monitoring should remain for succeeding fluent text. To test our assumptions, half of the students (n = 32) first learned with a disfluent (deleted letter) text and then with a fluent (intact) text. Results show no differences in monitoring between the disfluent and the fluent text. This supports our assumption that disfluency activates analytic monitoring that remains for succeeding fluent text. When the other half of the students (n = 33) first learned with a fluent and then with a disfluent text, differences in monitoring between the disfluent and the fluent text were found. Performance was significantly affected by fluency but in favor of the fluent texts, and hence, disfluency did not activate analytic cognitive processing. Thus, difficulties can foster analytic monitoring that remains for succeeding fluent text, but they do not necessarily improve performance. Further research is required to investigate how analytic monitoring can lead to improved cognitive processing and performance. KW - metacomprehension KW - disfluency KW - metacognitive monitoring KW - metacognitive control KW - metacognitive judgments KW - desirable difficulties Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197179 SN - 2504-284X VL - 3 IS - 101 ER - TY - JOUR A1 - Bar-Yosef, Hagit A1 - Gildor, Tsvia A1 - Ramírez-Zavala, Bernardo A1 - Schmauch, Christian A1 - Weissman, Ziva A1 - Pinsky, Mariel A1 - Naddaf, Rawi A1 - Morschhäuser, Joachim A1 - Arkowitz, Robert A. A1 - Kornitzer, Daniel T1 - A global analysis of kinase function in Candida albicans hyphal morphogenesis reveals a role for the endocytosis regulator Akl1 JF - Frontiers in Cellular and Infection Microbiology N2 - The human pathogenic fungus Candida albicans can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of C. albicans protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter. Proportionately more phosphatases than kinases were identified that inhibited hyphal morphogenesis, consistent with the known role of protein phosphorylation in hyphal induction. Among the kinases, we identified AKL1 as a gene that significantly suppressed hyphal morphogenesis in serum. Akl1 specifically affected hyphal elongation rather than initiation: overexpression of AKL1 repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the absence of Akl1, the Pan1 patches were delocalized from the sub-apical region, and fluid-phase endocytosis was intensified. These results underscore the requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore, these results suggest that under standard conditions, endocytosis is rate-limiting for hyphal elongation. KW - hyphae KW - endocytosis KW - Pan1 KW - functional genomics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197204 SN - 2235-2988 VL - 8 ER - TY - JOUR A1 - Nadella, Vinod A1 - Mohanty, Aparna A1 - Sharma, Lalita A1 - Yellaboina, Sailu A1 - Mollenkopf, Hans-Joachim A1 - Mazumdar, Varadendra Balaji A1 - Palaparthi, Ramesh A1 - Mylavarapu, Madhavi B. A1 - Maurya, Radheshyam A1 - Kurukuti, Sreenivasulu A1 - Rudel, Thomas A1 - Prakash, Hridayesh T1 - Inhibitors of Apoptosis Protein Antagonists (Smac Mimetic Compounds) Control Polarization of Macrophages during Microbial Challenge and Sterile Inflammatory Responses JF - Frontiers in Immunology N2 - Apoptosis is a physiological cell death process essential for development, tissue homeostasis, and for immune defense of multicellular animals. Inhibitors of apoptosis proteins (IAPs) regulate apoptosis in response to various cellular assaults. Using both genetic and pharmacological approaches we demonstrate here that the IAPs not only support opportunistic survival of intracellular human pathogens like Chlamydia pneumoniae but also control plasticity of iNOS+ M1 macrophage during the course of infection and render them refractory for immune stimulation. Treatment of Th1 primed macrophages with birinapant (IAP-specific antagonist) inhibited NO generation and relevant proteins involved in innate immune signaling. Accordingly, birinapant promoted hypoxia, angiogenesis, and tumor-induced M2 polarization of iNOS+ M1 macrophages. Interestingly, birinapant-driven changes in immune signaling were accompanied with changes in the expression of various proteins involved in the metabolism, and thus revealing the new role of IAPs in immune metabolic reprogramming in committed macrophages. Taken together, our study reveals the significance of IAP targeting approaches (Smac mimetic compounds) for the management of infectious and inflammatory diseases relying on macrophage plasticity. KW - apoptosis KW - macrophages immunobiology KW - inflammation mediators KW - polarization KW - infection KW - hypothalamus Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197484 SN - 1664-3224 VL - 8 IS - 1792 ER - TY - JOUR A1 - Prauße, Maria T. E. A1 - Lehnert, Teresa A1 - Timme, Sandra A1 - Hünniger, Kerstin A1 - Leonhardt, Ines A1 - Kurzai, Oliver A1 - Figge, Marc Thilo T1 - Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood JF - Frontiers in Immunology N2 - Bloodstream infections by the human-pathogenic fungi Candida albicans and Candida glabrata increasingly occur in hospitalized patients and are associated with high mortality rates. The early immune response against these fungi in human blood comprises a concerted action of humoral and cellular components of the innate immune system. Upon entering the blood, the majority of fungal cells will be eliminated by innate immune cells, i.e., neutrophils and monocytes. However, recent studies identified a population of fungal cells that can evade the immune response and thereby may disseminate and cause organ dissemination, which is frequently observed during candidemia. In this study, we investigate the so far unresolved mechanism of fungal immune evasion in human whole blood by testing hypotheses with the help of mathematical modeling. We use a previously established state-based virtual infection model for whole-blood infection with C. albicans to quantify the immune response and identified the fungal immune-evasion mechanism. While this process was assumed to be spontaneous in the previous model, we now hypothesize that the immune-evasion process is mediated by host factors and incorporate such a mechanism in the model. In particular, we propose, based on previous studies that the fungal immune-evasion mechanism could possibly arise through modification of the fungal surface by as of yet unknown proteins that are assumed to be secreted by activated neutrophils. To validate or reject any of the immune-evasion mechanisms, we compared the simulation of both immune-evasion models for different infection scenarios, i.e., infection of whole blood with either C. albicans or C. glabrata under non-neutropenic and neutropenic conditions. We found that under non-neutropenic conditions, both immune-evasion models fit the experimental data from whole-blood infection with C. albicans and C. glabrata. However, differences between the immune-evasion models could be observed for the infection outcome under neutropenic conditions with respect to the distribution of fungal cells across the immune cells. Based on these predictions, we suggested specific experimental studies that might allow for the validation or rejection of the proposed immune-evasion mechanism. KW - immune evasion KW - state-based model KW - innate immune response KW - polymorphonuclear neutrophils KW - whole-blood infection assay Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197493 SN - 1664-3224 VL - 9 IS - 560 ER - TY - JOUR A1 - Muhammad, Khalid A1 - Rudolf, Ronald A1 - Pham, Duong Anh Thuy A1 - Klein-Hessling, Stefan A1 - Takata, Katsuyoshi A1 - Matsushita, Nobuko A1 - Ellenrieder, Volker A1 - Kondo, Eisaku A1 -  Serfling, Edgar T1 - Induction of Short NFATc1/αA Isoform Interferes with Peripheral B Cell Differentiation JF - Frontiers in Immunology N2 - In lymphocytes, immune receptor signals induce the rapid nuclear translocation of preformed cytosolic NFAT proteins. Along with co-stimulatory signals, persistent immune receptor signals lead to high levels of NFATc1/αA, a short NFATc1 isoform, in effector lymphocytes. Whereas NFATc1 is not expressed in plasma cells, in germinal centers numerous centrocytic B cells express nuclear NFATc1/αA. When overexpressed in chicken DT40 B cells or murine WEHI 231 B cells, NFATc1/αA suppressed their cell death induced by B cell receptor signals and affected the expression of genes controlling the germinal center reaction and plasma cell formation. Among those is the Prdm1 gene encoding Blimp-1, a key factor of plasma cell formation. By binding to a regulatory DNA element within exon 1 of the Prdm1 gene, NFATc1/αA suppresses Blimp-1 expression. Since expression of a constitutive active version of NFATc1/αA interfered with Prdm1 RNA expression, LPS-mediated differentiation of splenic B cells to plasmablasts in vitro and reduced immunoglobulin production in vivo, one may conclude that NFATc1/αA plays an important role in controlling plasmablast/plasma cell formation. KW - B cells KW - DT40 cells KW - germinal center KW - NFATc1 KW - plasmablasts KW - plasma cells Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197501 SN - 1664-3224 VL - 9 IS - 32 ER - TY - JOUR A1 - Volpato, Daniela A1 - Holzgrabe, Ulrike T1 - Designing Hybrids Targeting the Cholinergic System by Modulating the Muscarinic and Nicotinic Receptors: A Concept to Treat Alzheimer’s Disease JF - Molecules N2 - The cholinergic hypothesis has been reported first being the cause of memory dysfunction in the Alzheimer’s disease. Researchers around the globe have focused their attention on understanding the mechanisms of how this complicated system contributes to processes such as learning, memory, disorientation, linguistic problems, and behavioral issues in the indicated chronic neurodegenerative disease. The present review reports recent updates in hybrid molecule design as a strategy for selectively addressing multiple target proteins involved in Alzheimer’s disease (AD) and the study of their therapeutic relevance. The rationale and the design of the bifunctional compounds will be discussed in order to understand their potential as tools to investigate the role of the cholinergic system in AD. KW - AChE inhibitor KW - Alzheimer’s disease KW - bitopic ligand KW - cholinergic system KW - hybrid molecules KW - muscarinic receptors KW - nicotinic receptors Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197555 SN - 1420-3049 VL - 23 IS - 12 ER - TY - JOUR A1 - Zielewska-Büttner, Katarzyna A1 - Heurich, Marco A1 - Müller, Jörg A1 - Braunisch, Veronika T1 - Remotely Sensed Single Tree Data Enable the Determination of Habitat Thresholds for the Three-Toed Woodpecker (Picoides tridactylus) JF - Remote Sensing N2 - Forest biodiversity conservation requires precise, area-wide information on the abundance and distribution of key habitat structures at multiple spatial scales. We combined airborne laser scanning (ALS) data with color-infrared (CIR) aerial imagery for identifying individual tree characteristics and quantifying multi-scale habitat requirements using the example of the three-toed woodpecker (Picoides tridactylus) (TTW) in the Bavarian Forest National Park (Germany). This bird, a keystone species of boreal and mountainous forests, is highly reliant on bark beetles dwelling in dead or dying trees. While previous studies showed a positive relationship between the TTW presence and the amount of deadwood as a limiting resource, we hypothesized a unimodal response with a negative effect of very high deadwood amounts and tested for effects of substrate quality. Based on 104 woodpecker presence or absence locations, habitat selection was modelled at four spatial scales reflecting different woodpecker home range sizes. The abundance of standing dead trees was the most important predictor, with an increase in the probability of TTW occurrence up to a threshold of 44–50 dead trees per hectare, followed by a decrease in the probability of occurrence. A positive relationship with the deadwood crown size indicated the importance of fresh deadwood. Remote sensing data allowed both an area-wide prediction of species occurrence and the derivation of ecological threshold values for deadwood quality and quantity for more informed conservation management. KW - deadwood KW - standing deadwood KW - dead tree KW - snags KW - three-toed woodpecker (Picoides tridactylus) KW - habitat suitability model (HSM) KW - habitat requirements KW - airborne laser scanning (ALS) KW - CIR aerial imagery Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197565 SN - 2072-4292 VL - 10 IS - 12 ER - TY - JOUR A1 - Zimmerer, Chris A1 - Fischbach, Martin A1 - Latoschik, Marc Erich T1 - Semantic Fusion for Natural Multimodal Interfaces using Concurrent Augmented Transition Networks JF - Multimodal Technologies and Interaction N2 - Semantic fusion is a central requirement of many multimodal interfaces. Procedural methods like finite-state transducers and augmented transition networks have proven to be beneficial to implement semantic fusion. They are compliant with rapid development cycles that are common for the development of user interfaces, in contrast to machine-learning approaches that require time-costly training and optimization. We identify seven fundamental requirements for the implementation of semantic fusion: Action derivation, continuous feedback, context-sensitivity, temporal relation support, access to the interaction context, as well as the support of chronologically unsorted and probabilistic input. A subsequent analysis reveals, however, that there is currently no solution for fulfilling the latter two requirements. As the main contribution of this article, we thus present the Concurrent Cursor concept to compensate these shortcomings. In addition, we showcase a reference implementation, the Concurrent Augmented Transition Network (cATN), that validates the concept’s feasibility in a series of proof of concept demonstrations as well as through a comparative benchmark. The cATN fulfills all identified requirements and fills the lack amongst previous solutions. It supports the rapid prototyping of multimodal interfaces by means of five concrete traits: Its declarative nature, the recursiveness of the underlying transition network, the network abstraction constructs of its description language, the utilized semantic queries, and an abstraction layer for lexical information. Our reference implementation was and is used in various student projects, theses, as well as master-level courses. It is openly available and showcases that non-experts can effectively implement multimodal interfaces, even for non-trivial applications in mixed and virtual reality. KW - multimodal fusion KW - multimodal interface KW - semantic fusion KW - procedural fusion methods KW - natural interfaces KW - human-computer interaction Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197573 SN - 2414-4088 VL - 2 IS - 4 ER - TY - JOUR A1 - Romoli, Carlo A1 - Chakraborty, Nachiketa A1 - Dorner, Daniela A1 - Taylor, Andrew A1 - Blank, Michael T1 - Flux Distribution of Gamma-Ray Emission in Blazars: The Example of Mrk 501 JF - Galaxies N2 - Flux distribution is an important tool to understand the variability processes in activegalactic nuclei. We now have available a great deal of observational evidences pointing towards thepresence of log-normal components in the high energy light curves, and different models have beenproposed to explain these data. Here, we collect some of the recent developments on this topic usingthe well-known blazar Mrk 501 as example of complex and interesting aspects coming from its fluxdistribution in different energy ranges and at different timescales. The observational data we refer toare those collected in a complementary manner by Fermi-LAT over multiple years, and by the FirstG-APD Cherenkov Telescope (FACT) telescope and the H.E.S.S. array in correspondence of the brightflare of June 2014 KW - gamma rays KW - very high energy KW - active galactic nuclei KW - Markarian 501 KW - monitoring KW - flux distributions Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197580 SN - 2075-4434 VL - 6 IS - 4 ER - TY - CHAP A1 - Schmitz, Barbara T1 - King and God : conceptions of rule and God in 3 Maccabees T2 - Figures who shape scriptures, scriptures that shape figures N2 - In 3 Maccabees, kingship as a form of rule is addressed on two levels: On the political level the question about a good king is addressed against the background of Hellenistic understandings of kingship, using the example of Ptolemy IV Philopator. This king is portrayed at the beginning of 3 Maccabees as a successful, positive, Hellenistic ruler, but one whose good rule goes off the rails. This analysis of the ideal of Hellenistic rule (cf. 3 Macc. 3:12-29; 6:24-28; 7:1-9) is then taken to a theological level: the God of Israel is portrayed as the true good king, the Soter who saves his people in their time of greatest trial (6:29, 32; 7:16). By these means the many divine epithets that are a striking feature of 3 Maccabees are incorporated into the narrative (cf. 2:2-3). Thereby 3 Maccabees not only thematises the conflict with a Hellenistic king who exploits his power in diverse ways but also focuses in a concentrated way the notion of a good (Hellenistic) king into the notion of God as king and ruler. KW - Maccabees KW - Hellenistic kingship KW - Xenophon KW - Cyropaidia KW - Isocrates KW - God in 3 Macc Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205149 ER - TY - JOUR A1 - Grande, Vincenzo A1 - Soberats, Bartolome A1 - Herbst, Stefanie A1 - Stepanenko, Vladimir A1 - Würthner, Frank T1 - Hydrogen-bonded perylene bisimide J-aggregate aqua material N2 - A new twelvefold methoxy-triethyleneglycol-jacketed tetraphenoxy-perylene bisimide (MEG-PBI) amphiphile was synthesized that self-assembles into two types of supramolecular aggregates in water: red-coloured aggregates of low order and with weak exciton coupling among the PBIs and blue-coloured strongly coupled J-aggregates consisting of a highly ordered hydrogen-bonded triple helix of PBIs. At room temperature this PBI is miscible with water at any proportions which enables the development of robust dye aggregates in solution, in hydrogel states and in lyotropic liquid crystalline states. In the presence of 60–95 wt% water, self-standing coloured hydrogels exhibit colour changes from red to blue accompanied by a fluorescence light-up in the far-red region upon heating in the range of 30–50 °C. This phenomenon is triggered by an entropically driven temperature-induced hydrogen-bond-directed slipped stacking arrangement of the MEG-PBI chromophores within structurally well-defined J-aggregates. This versatile aqua material is the first example of a stable PBI J-aggregate in water. We anticipate that this study will open a new avenue for the development of biocompatible functional materials based on self-assembled dyes and inspire the construction of other hydrogen-bonded supramolecular materials in the highly competitive solvent water. KW - self-assembly KW - dyes KW - aqua material Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204715 UR - https://doi.org/10.1039/C8SC02409J SN - 2041-6539 VL - 9 ER - TY - JOUR A1 - Hagg, Wilfried A1 - Mayr, Elisabeth A1 - Mannig, Birgit A1 - Reyers, Mark A1 - Schubert, David A1 - Pinto, Joaquim G. A1 - Peters, Juliane A1 - Pieczonka, Tino A1 - Juen, Martin A1 - Bolch, Tobias A1 - Paeth, Heiko A1 - Mayer, Christoph T1 - Future climate change and its impact on runoff generation from the debris-covered Inylchek glaciers, Central Tian Shan, Kyrgyzstan JF - Water N2 - The heavily debris-covered Inylchek glaciers in the central Tian Shan are the largest glacier system in the Tarim catchment. It is assumed that almost 50% of the discharge of Tarim River are provided by glaciers. For this reason, climatic changes, and thus changes in glacier mass balance and glacier discharge are of high impact for the whole region. In this study, a conceptual hydrological model able to incorporate discharge from debris-covered glacier areas is presented. To simulate glacier melt and subsequent runoff in the past (1970/1971–1999/2000) and future (2070/2071–2099/2100), meteorological input data were generated based on ECHAM5/MPI-OM1 global climate model projections. The hydrological model HBV-LMU was calibrated by an automatic calibration algorithm using runoff and snow cover information as objective functions. Manual fine-tuning was performed to avoid unrealistic results for glacier mass balance. The simulations show that annual runoff sums will increase significantly under future climate conditions. A sensitivity analysis revealed that total runoff does not decrease until the glacier area is reduced by 43%. Ice melt is the major runoff source in the recent past, and its contribution will even increase in the coming decades. Seasonal changes reveal a trend towards enhanced melt in spring, but a change from a glacial-nival to a nival-pluvial runoff regime will not be reached until the end of this century. KW - glaciers KW - debris-covered glaciers KW - hydrological modelling KW - climate scenarios KW - Tian Shan Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197592 SN - 2073-4441 VL - 10 IS - 11 ER - TY - JOUR A1 - Weis, Matthias A1 - Shan, Junwen A1 - Kuhlmann, Matthias A1 - Jungst, Tomasz A1 - Tessmar, Jörg A1 - Groll, Jürgen T1 - Evaluation of hydrogels based on oxidized hyaluronic acid for bioprinting JF - Gels N2 - In this study, we evaluate hydrogels based on oxidized hyaluronic acid, cross-linked with adipic acid dihydrazide, for their suitability as bioinks for 3D bioprinting. Aldehyde containing hyaluronic acid (AHA) is synthesized and cross-linked via Schiff Base chemistry with bifunctional adipic acid dihydrazide (ADH) to form a mechanically stable hydrogel with good printability. Mechanical and rheological properties of the printed and casted hydrogels are tunable depending on the concentrations of AHA and ADH cross-linkers. KW - biofabrication KW - bioprinting KW - hyaluronic acid Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197600 SN - 2310-2861 VL - 4 IS - 4 ER - TY - JOUR A1 - Khan, Muhammad Usman A1 - Pirzadeh, Maryam A1 - Förster, Carola Yvette A1 - Shityakov, Sergey A1 - Shariati, Mohammad Ali T1 - Role of milk-derived antibacterial peptides in modern food biotechnology: their synthesis, applications and future perspectives JF - Biomolecules N2 - Milk-derived antibacterial peptides (ABPs) are protein fragments with a positive influence on the functions and conditions of a living organism. Milk-derived ABPs have several useful properties important for human health, comprising a significant antibacterial effect against various pathogens, but contain toxic side-effects. These compounds are mainly produced from milk proteins via fermentation and protein hydrolysis. However, they can also be produced using recombinant DNA techniques or organic synthesis. This review describes the role of milk-derived ABPs in modern food biotechnology with an emphasis on their synthesis and applications. Additionally, we also discuss the mechanisms of action and the main bioproperties of ABPs. Finally, we explore future perspectives for improving ABP physicochemical properties and diminishing their toxic side-effects. KW - milk proteins KW - bioactive peptide KW - antibacterial activity KW - fermentation KW - protein hydrolysis KW - recombinant DNA KW - peptide synthesis Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197610 SN - 2218-273X VL - 8 IS - 4 ER - TY - JOUR A1 - Marzocco, Stefania A1 - Fazeli, Gholamreza A1 - Di Micco, Lucia A1 - Autore, Giuseppina A1 - Adesso, Simona A1 - Dal Piaz, Fabrizio A1 - Heidland, August A1 - Di Iorio, Biagio T1 - Supplementation of short-chain fatty acid, sodium propionate, in patients on maintenance hemodialysis: beneficial effects on inflammatory parameters and gut-derived uremic toxins, a pilot study (PLAN Study) JF - Journal of Clinical Medicine N2 - Background: In end-stage renal disease (ESRD), gut-derived uremic toxins play a crucial role in the systemic inflammation and oxidative stress promoting the excess morbidity and mortality. The biochemical derangement is in part a consequence of an insufficient generation of short-chain fatty acids (SCFA) due to the dysbiosis of the gut and an insufficient consumption of the fermentable complex carbohydrates. Aim of the study: The primary end-point was to evaluate the potential efficacy of SCFA (specifically, sodium propionate (SP)) for patients on maintenance hemodialysis (MHD) on systemic inflammation. Secondary end-points included potential attenuation of oxidative stress markers, insulin resistance and production of gut-derived uremic toxins indoxyl sulfate and p-cresol sulfate, as well as health status after SP supplementation. Study design: We performed a single-center non-randomized pilot study in 20 MHD patients. They received the food additive SP with a daily intake of 2 × 500 mg in the form of capsules for 12 weeks. Pre-dialysis blood samples were taken at the beginning, after six weeks and at the end of the administration period, as well as four weeks after withdrawal of the treatment. Results: The subjects revealed a significant decline of inflammatory parameters C-reactive protein (−46%), interleukin IL-2 (−27%) and IL-17 (−15%). The inflammatory parameters IL-6 and IFN-gamma showed a mild non-significant reduction and the anti-inflammatory cytokine IL-10 increased significantly (+71%). While the concentration of bacterial endotoxins and TNF-α remained unchanged, the gut-derived uremic toxins, indoxyl sulfate (−30%) and p-cresyl sulfate (−50%), revealed a significant decline. The SP supplementation reduced the parameters of oxidative stress malondialdehyde (−32%) and glutathione peroxidase activity (−28%). The serum insulin levels dropped by 30% and the HOMA-index by 32%. The reduction of inflammatory parameters was associated with a lowering of ferritin and a significant increase in transferrin saturation (TSAT). Four weeks after the end of the treatment phase, all improved parameters deteriorated again. Evaluation of the psycho-physical performance with the short form 36 (SF-36) questionnaire showed an enhancement in the self-reported physical functioning, general health, vitality and mental health. The SP supplementation was well tolerated and without important side effects. No patient had left the study due to intolerance to the medication. The SP supplementation in MHD patients reduced pro-inflammatory parameters and oxidative stress and improved insulin resistance and iron metabolism. Furthermore, SP effectively lowered the important gut-derived uremic toxins indoxyl and p-cresol sulfate. These improvements were associated with a better quality of life. Further controlled studies are required in a larger cohort to evaluate the clinical outcome. KW - propionic acid KW - chronic kidney disease KW - hemodialysis KW - gut microbiome KW - systemic micro-inflammation oxidative stress KW - indoxyl sulfate KW - p-cresyl sulfate Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197626 SN - 2077-0383 VL - 7 IS - 10 ER - TY - JOUR A1 - Yanku, Yifat A1 - Bitman-Lotan, Eliya A1 - Zohar, Yaniv A1 - Kurant, Estee A1 - Zilke, Norman A1 - Eilers, Martin A1 - Orian, Amir T1 - Drosophila HUWE1 ubiquitin ligase regulates endoreplication and antagonizes JNK signaling during salivary gland development JF - Cells N2 - The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress and immune signaling, mitochondria homeostasis, and cell death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster and Humans. Here, we report that the Drosophila ortholog, dHUWE1 (CG8184), is an essential gene whose loss results in embryonic lethality and whose tissue-specific disruption establishes its regulatory role in larval salivary gland development. dHUWE1 is essential for endoreplication of salivary gland cells and its knockdown results in the inability of these cells to replicate DNA. Remarkably, dHUWE1 is a survival factor that prevents premature activation of JNK signaling, thus preventing the disintegration of the salivary gland, which occurs physiologically during pupal stages. This function of dHUWE1 is general, as its inhibitory effect is observed also during eye development and at the organismal level. Epistatic studies revealed that the loss of dHUWE1 is compensated by dMyc proeitn expression or the loss of dmP53. dHUWE1 is therefore a conserved survival factor that regulates organ formation during Drosophila development. KW - HECT KW - HUWE1 KW - ubiquitin KW - salivary gland KW - endoreplication KW - JNK KW - dMyc KW - dmP53 Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197630 SN - 2073-4409 VL - 7 IS - 10 ER - TY - JOUR A1 - Bura, Thomas A1 - Beaupré, Serge A1 - Légaré, Marc-André A1 - Ibraikulov, Olzhas A. A1 - Leclerc, Nicolas A1 - Leclerc, Mario T1 - Theoretical calculations for highly selective Direct Heteroarylation Polymerization: new nitrile-substituted Dithienyl-Diketopyrrolopyrrole-based polymers JF - Molecules N2 - Direct Heteroarylation Polymerization (DHAP) is becoming a valuable alternative to classical polymerization methods being used to synthesize π-conjugated polymers for organic electronics applications. In previous work, we showed that theoretical calculations on activation energy (Ea) of the C–H bonds were helpful to rationalize and predict the selectivity of the DHAP. For readers’ convenience, we have gathered in this work all our previous theoretical calculations on Ea and performed new ones. Those theoretical calculations cover now most of the widely utilized electron-rich and electron-poor moieties studied in organic electronics like dithienyl-diketopyrrolopyrrole (DT-DPP) derivatives. Theoretical calculations reported herein show strong modulation of the Ea of C–H bond on DT-DPP when a bromine atom or strong electron withdrawing groups (such as fluorine or nitrile) are added to the thienyl moiety. Based on those theoretical calculations, new cyanated dithienyl-diketopyrrolopyrrole (CNDT-DPP) monomers and copolymers were prepared by DHAP and their electro-optical properties were compared with their non-fluorinated and fluorinated analogues. KW - DHAP KW - selectivity KW - theoretical calculations KW - conjugated polymers KW - organic electronics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197648 SN - 1420-3049 VL - 23 IS - 9 ER - TY - JOUR A1 - Nyamekye, Clement A1 - Thiel, Michael A1 - Schönbrodt-Stitt, Sarah A1 - Zoungrana, Benewinde J.-B. A1 - Amekudzi, Leonard K. T1 - Soil and water conservation in Burkina Faso, West Africa JF - Sustainability N2 - Inadequate land management and agricultural activities have largely resulted in land degradation in Burkina Faso. The nationwide governmental and institutional driven implementation and adoption of soil and water conservation measures (SWCM) since the early 1960s, however, is expected to successively slow down the degradation process and to increase the agricultural output. Even though relevant measures have been taken, only a few studies have been conducted to quantify their effect, for instance, on soil erosion and environmental restoration. In addition, a comprehensive summary of initiatives, implementation strategies, and eventually region-specific requirements for adopting different SWCM is missing. The present study therefore aims to review the different SWCM in Burkina Faso and implementation programs, as well as to provide information on their effects on environmental restoration and agricultural productivity. This was achieved by considering over 143 studies focusing on Burkina Faso’s experience and research progress in areas of SWCM and soil erosion. SWCM in Burkina Faso have largely resulted in an increase in agricultural productivity and improvement in food security. Finally, this study aims at supporting the country’s informed decision-making for extending already existing SWCM and for deriving further implementation strategies. KW - soil and water conservation KW - environmental degradation KW - agricultural productivity KW - food security KW - soil erosion KW - Burkina Faso Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197653 SN - 2071-1050 VL - 10 IS - 9 ER - TY - JOUR A1 - Bencurova, Elena A1 - Gupta, Shishir K. A1 - Sarukhanyan, Edita A1 - Dandekar, Thomas T1 - Identification of antifungal targets based on computer modeling JF - Journal of Fungi N2 - Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to analyze possible targeting strategies on fungal-unique pathways. For instance, phylogenetic analysis reveals fungal targets, while domain analysis allows us to spot minor differences in protein composition between the host and fungi. Moreover, protein networks between host and fungi can be systematically compared by looking at orthologs and exploiting information from host–pathogen interaction databases. Further data—such as knowledge of a three-dimensional structure, gene expression data, or information from calculated metabolic fluxes—refine the search and rapidly put a focus on the best targets for antimycotics. We analyzed several of the best targets for application to structure-based drug design. Finally, we discuss general advantages and limitations in identification of unique fungal pathways and protein targets when applying bioinformatics tools. KW - Aspergillus KW - metabolic pathways KW - computational modelling KW - drug design Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197670 SN - 2309-608X VL - 4 IS - 3 ER - TY - JOUR A1 - Lausch, Angela A1 - Borg, Erik A1 - Bumberger, Jan A1 - Dietrich, Peter A1 - Heurich, Marco A1 - Huth, Andreas A1 - Jung, András A1 - Klenke, Reinhard A1 - Knapp, Sonja A1 - Mollenhauer, Hannes A1 - Paasche, Hendrik A1 - Paulheim, Heiko A1 - Pause, Marion A1 - Schweitzer, Christian A1 - Schmulius, Christiane A1 - Settele, Josef A1 - Skidmore, Andrew K. A1 - Wegmann, Martin A1 - Zacharias, Steffen A1 - Kirsten, Toralf A1 - Schaepman, Michael E. T1 - Understanding forest health with remote sensing, part III: requirements for a scalable multi-source forest health monitoring network based on data science approaches JF - Remote Sensing N2 - Forest ecosystems fulfill a whole host of ecosystem functions that are essential for life on our planet. However, an unprecedented level of anthropogenic influences is reducing the resilience and stability of our forest ecosystems as well as their ecosystem functions. The relationships between drivers, stress, and ecosystem functions in forest ecosystems are complex, multi-faceted, and often non-linear, and yet forest managers, decision makers, and politicians need to be able to make rapid decisions that are data-driven and based on short and long-term monitoring information, complex modeling, and analysis approaches. A huge number of long-standing and standardized forest health inventory approaches already exist, and are increasingly integrating remote-sensing based monitoring approaches. Unfortunately, these approaches in monitoring, data storage, analysis, prognosis, and assessment still do not satisfy the future requirements of information and digital knowledge processing of the 21st century. Therefore, this paper discusses and presents in detail five sets of requirements, including their relevance, necessity, and the possible solutions that would be necessary for establishing a feasible multi-source forest health monitoring network for the 21st century. Namely, these requirements are: (1) understanding the effects of multiple stressors on forest health; (2) using remote sensing (RS) approaches to monitor forest health; (3) coupling different monitoring approaches; (4) using data science as a bridge between complex and multidimensional big forest health (FH) data; and (5) a future multi-source forest health monitoring network. It became apparent that no existing monitoring approach, technique, model, or platform is sufficient on its own to monitor, model, forecast, or assess forest health and its resilience. In order to advance the development of a multi-source forest health monitoring network, we argue that in order to gain a better understanding of forest health in our complex world, it would be conducive to implement the concepts of data science with the components: (i) digitalization; (ii) standardization with metadata management after the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles; (iii) Semantic Web; (iv) proof, trust, and uncertainties; (v) tools for data science analysis; and (vi) easy tools for scientists, data managers, and stakeholders for decision-making support. KW - forest health KW - in situ forest monitoring KW - remote sensing KW - data science KW - digitalization KW - big data KW - semantic web KW - linked open data KW - FAIR KW - multi-source forest health monitoring network Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197691 SN - 2072-4292 VL - 10 IS - 7 ER - TY - JOUR A1 - Dittmann, Jonas A1 - Balles, Andreas A1 - Zabler, Simon T1 - Optimization based evaluation of grating interferometric phase stepping series and analysis of mechanical setup instabilities JF - Journal of Imaging N2 - The diffraction contrast modalities accessible by X-ray grating interferometers are not imaged directly but have to be inferred from sine-like signal variations occurring in a series of images acquired at varying relative positions of the interferometer’s gratings. The absolute spatial translations involved in the acquisition of these phase stepping series usually lie in the range of only a few hundred nanometers, wherefore positioning errors as small as 10 nm will already translate into signal uncertainties of 1–10% in the final images if not accounted for. Classically, the relative grating positions in the phase stepping series are considered input parameters to the analysis and are, for the Fast Fourier Transform that is typically employed, required to be equidistantly distributed over multiples of the gratings’ period. In the following, a fast converging optimization scheme is presented simultaneously determining the phase stepping curves’ parameters as well as the actually performed motions of the stepped grating, including also erroneous rotational motions which are commonly neglected. While the correction of solely the translational errors along the stepping direction is found to be sufficient with regard to the reduction of image artifacts, the possibility to also detect minute rotations about all axes proves to be a valuable tool for system calibration and monitoring. The simplicity of the provided algorithm, in particular when only considering translational errors, makes it well suitable as a standard evaluation procedure also for large image series. KW - X-ray imaging KW - Talbot–Lau interferometer KW - grating interferometer KW - phase contrast imaging KW - darkfield imaging KW - phase stepping KW - optimization Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197723 SN - 2313-433X VL - 4 IS - 6 ER - TY - JOUR A1 - Boehm, Anne A1 - Meininger, Susanne A1 - Tesch, Annemarie A1 - Gbureck, Uwe A1 - Müller, Frank A. T1 - The mechanical properties of biocompatible apatite bone cement reinforced with chemically activated carbon fibers JF - Materials N2 - Calcium phosphate cement (CPC) is a well-established bone replacement material in dentistry and orthopedics. CPC mimics the physicochemical properties of natural bone and therefore shows excellent in vivo behavior. However, due to their brittleness, the application of CPC implants is limited to non-load bearing areas. Generally, the fiber-reinforcement of ceramic materials enhances fracture resistance, but simultaneously reduces the strength of the composite. Combining strong C-fiber reinforcement with a hydroxyapatite to form a CPC with a chemical modification of the fiber surface allowed us to adjust the fiber–matrix interface and consequently the fracture behavior. Thus, we could demonstrate enhanced mechanical properties of CPC in terms of bending strength and work of fracture to a strain of 5% (WOF5). Hereby, the strength increased by a factor of four from 9.2 ± 1.7 to 38.4 ± 1.7 MPa. Simultaneously, the WOF5 increased from 0.02 ± 0.004 to 2.0 ± 0.6 kJ∙m−2, when utilizing an aqua regia/CaCl2 pretreatment. The cell proliferation and activity of MG63 osteoblast-like cells as biocompatibility markers were not affected by fiber addition nor by fiber treatment. CPC reinforced with chemically activated C-fibers is a promising bone replacement material for load-bearing applications. KW - calcium phosphate cement KW - damage tolerant cement KW - carbon fiber reinforcement KW - interface control KW - fiber–matrix interaction Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197808 SN - 1996-1944 VL - 11 IS - 2 ER - TY - JOUR A1 - Wei, Chunzhu A1 - Blaschke, Thomas T1 - Pixel-wise vs. object-based impervious surface analysis from remote sensing: correlations with land surface temperature and population density JF - Urban Science N2 - Impervious surface areas (ISA) are heavily influenced by urban structure and related structural features. We examined the effects of object-based impervious surface spatial pattern analysis on land surface temperature and population density in Guangzhou, China, in comparison to classic per-pixel analyses. An object-based support vector machine (SVM) and a linear spectral mixture analysis (LSMA) were integrated to estimate ISA fraction using images from the Chinese HJ-1B satellite for 2009 to 2011. The results revealed that the integrated object-based SVM-LSMA algorithm outperformed the traditional pixel-wise LSMA algorithm in classifying ISA fraction. More specifically, the object-based ISA spatial patterns extracted were more suitable than pixel-wise patterns for urban heat island (UHI) studies, in which the UHI areas (landscape surface temperature >37 °C) generally feature high ISA fraction values (ISA fraction >50%). In addition, the object-based spatial patterns enable us to quantify the relationship of ISA with population density (correlation coefficient >0.2 in general), with global human settlement density (correlation coefficient >0.2), and with night-time light map (correlation coefficient >0.4), and, whereas pixel-wise ISA did not yield significant correlations. These results indicate that object-based spatial patterns have a high potential for UHI detection and urbanization monitoring. Planning measures that aim to reduce the urbanization impacts and UHI intensities can be better supported. KW - impervious surface areas KW - object-based image analysis KW - land surface temperature KW - population density Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197829 SN - 2413-8851 VL - 2 IS - 1 ER - TY - INPR A1 - Titov, Evgenii A1 - Humeniuk, Alexander A1 - Mitric, Roland T1 - Exciton localization in excited-state dynamics of a tetracene trimer: A surface hopping LC-TDDFTB study T2 - Physical Chemistry Chemical Physics N2 - Excitons in the molecular aggregates of chromophores are key participants in important processes such as photosynthesis or the functioning of organic photovoltaic devices. Therefore, the exploration of exciton dynamics is crucial. Here we report on exciton localization during excited-state dynamics of the recently synthesized tetracene trimer [Liu et al., Org. Lett., 2017, 19, 580]. We employ the surface hopping approach to nonadiabatic molecular dynamics in conjunction with the long-range corrected time-dependent density functional tight binding (LC-TDDFTB) method [Humeniuk and Mitrić, Comput. Phys. Commun., 2017, 221, 174]. Utilizing a set of descriptors based on the transition density matrix, we perform comprehensive analysis of exciton dynamics. The obtained results reveal an ultrafast exciton localization to a single tetracene unit of the trimer during excited-state dynamics, along with exciton transfer between units. KW - Exciton dynamics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198680 UR - https://doi.org/10.1039/C8CP05240A N1 - Accepted Manuscript ER - TY - JOUR A1 - Madan, Christopher R. A1 - Bayer, Janine A1 - Gamer, Matthias A1 - Lonsdorf, Tina B. A1 - Sommer, Tobias T1 - Visual Complexity and Affect: Ratings Reflect More Than Meets the Eye JF - Frontiers in Psychology N2 - Pictorial stimuli can vary on many dimensions, several aspects of which are captured by the term ‘visual complexity.’ Visual complexity can be described as, “a picture of a few objects, colors, or structures would be less complex than a very colorful picture of many objects that is composed of several components.” Prior studies have reported a relationship between affect and visual complexity, where complex pictures are rated as more pleasant and arousing. However, a relationship in the opposite direction, an effect of affect on visual complexity, is also possible; emotional arousal and valence are known to influence selective attention and visual processing. In a series of experiments, we found that ratings of visual complexity correlated with affective ratings, and independently also with computational measures of visual complexity. These computational measures did not correlate with affect, suggesting that complexity ratings are separately related to distinct factors. We investigated the relationship between affect and ratings of visual complexity, finding an ‘arousal-complexity bias’ to be a robust phenomenon. Moreover, we found this bias could be attenuated when explicitly indicated but did not correlate with inter-individual difference measures of affective processing, and was largely unrelated to cognitive and eyetracking measures. Taken together, the arousal-complexity bias seems to be caused by a relationship between arousal and visual processing as it has been described for the greater vividness of arousing pictures. The described arousal-complexity bias is also of relevance from an experimental perspective because visual complexity is often considered a variable to control for when using pictorial stimuli. KW - visual complexity KW - affect KW - arousal KW - valence KW - eyetracking KW - emotion Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190015 SN - 1664-1078 VL - 8 IS - 2368 ER - TY - JOUR A1 - Trafimow, David A1 - Amrhein, Valentin A1 - Areshenkoff, Corson N. A1 - Barrera-Causil, Carlos J. A1 - Beh, Eric J. A1 - Bilgiç, Yusuf K. A1 - Bono, Roser A1 - Bradley, Michael T. A1 - Briggs, William M. A1 - Cepeda-Freyre, Héctor A. A1 - Chaigneau, Sergio E. A1 - Ciocca, Daniel R. A1 - Correa, Juan C. A1 - Cousineau, Denis A1 - de Boer, Michiel R. A1 - Dhar, Subhra S. A1 - Dolgov, Igor A1 - Gómez-Benito, Juana A1 - Grendar, Marian A1 - Grice, James W. A1 - Guerrero-Gimenez, Martin E. A1 - Gutiérrez, Andrés A1 - Huedo-Medina, Tania B. A1 - Jaffe, Klaus A1 - Janyan, Armina A1 - Karimnezhad, Ali A1 - Korner-Nievergelt, Fränzi A1 - Kosugi, Koji A1 - Lachmair, Martin A1 - Ledesma, Rubén D. A1 - Limongi, Roberto A1 - Liuzza, Marco T. A1 - Lombardo, Rosaria A1 - Marks, Michael J. A1 - Meinlschmidt, Gunther A1 - Nalborczyk, Ladislas A1 - Nguyen, Hung T. A1 - Ospina, Raydonal A1 - Perezgonzalez, Jose D. A1 - Pfister, Roland A1 - Rahona, Juan J. A1 - Rodríguez-Medina, David A. A1 - Romão, Xavier A1 - Ruiz-Fernández, Susana A1 - Suarez, Isabel A1 - Tegethoff, Marion A1 - Tejo, Mauricio A1 - van de Schoot, Rens A1 - Vankov, Ivan I. A1 - Velasco-Forero, Santiago A1 - Wang, Tonghui A1 - Yamada, Yuki A1 - Zoppino, Felipe C. M. A1 - Marmolejo-Ramos, Fernando T1 - Manipulating the Alpha Level Cannot Cure Significance Testing JF - Frontiers in Psychology N2 - We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable. KW - statistical significance KW - null hypothesis testing KW - p-value KW - significance testing KW - decision making Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189973 SN - 1664-1078 VL - 9 IS - 699 ER - TY - JOUR A1 - Schwab, Frank A1 - Hennighausen, Christine A1 - Adler, Dorothea C. A1 - Carolus, Astrid T1 - Television Is Still “Easy” and Print Is Still “Tough”? More Than 30 Years of Research on the Amount of Invested Mental Effort JF - Frontiers in Psychology N2 - We provide a literature overview of 30 years of research on the amount of invested mental effort (AIME, Salomon, 1984), illuminating relevant literature in this field. Since the introduction of AIME, this concept appears to have vanished. To obtain a clearer picture of where the theory of AIME has diffused, we conducted a literature search focusing on the period 1985–2015. We examined scientific articles (N = 244) that cite Salomon (1984) and content-analyzed their keywords. Based on these keywords, we identified seven content clusters: affect and motivation, application fields, cognition and learning, education and teaching, media technology, learning with media technology, and methods. We present selected works of each content cluster and describe in which research field the articles had been published. Results indicate that AIME was most commonly (but not exclusively) referred to in the area of educational psychology indicating its importance regarding learning and education, thereby investigating print and TV, as well as new media. From a methodological perspective, research applied various research methods (e.g., longitudinal studies, experimental designs, theoretical analysis) and samples (e.g., children, college students, low income families). From these findings, the importance of AIME for further research is discussed. KW - AIME KW - amount of invested mental effort KW - literature review KW - content-analysis KW - content cluster Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189965 SN - 1664-1078 VL - 9 IS - 1098 ER - TY - JOUR A1 - Wolff, Hans-Georg A1 - Weikamp, Julia G. A1 - Batinic, Bernad T1 - Implicit Motives as Determinants of Networking Behaviors JF - Frontiers in Psychology N2 - In today’s world of work, networking behaviors are an important and viable strategy to enhance success in work and career domains. Concerning personality as an antecedent of networking behaviors, prior studies have exclusively relied on trait perspectives that focus on how people feel, think, and act. Adopting a motivational perspective on personality, we enlarge this focus and argue that beyond traits predominantly tapping social content, motives shed further light on instrumental aspects of networking – or why people network. We use McClelland’s implicit motives framework of need for power (nPow), need for achievement (nAch), and need for affiliation (nAff) to examine instrumental determinants of networking. Using a facet theoretical approach to networking behaviors, we predict differential relations of these three motives with facets of (1) internal vs. external networking and (2) building, maintaining, and using contacts. We conducted an online study, in which we temporally separate measures (N = 539 employed individuals) to examine our hypotheses. Using multivariate latent regression, we show that nAch is related to networking in general. In line with theoretical differences between networking facets, we find that nAff is positively related to building contacts, whereas nPow is positively related to using internal contacts. In sum, this study shows that networking is not only driven by social factors (i.e., nAff), but instead the achievement motive is the most important driver of networking behaviors. KW - networking KW - social capital KW - implicit motives KW - work behavior KW - social interaction KW - career self-management Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189954 SN - 1664-1078 VL - 9 IS - 411 ER - TY - JOUR A1 - Nagler, Matthias A1 - Nägele, Thomas A1 - Gilli, Christian A1 - Fragner, Lena A1 - Korte, Arthur A1 - Platzer, Alexander A1 - Farlow, Ashley A1 - Nordborg, Magnus A1 - Weckwerth, Wolfram T1 - Eco-Metabolomics and Metabolic Modeling: Making the Leap From Model Systems in the Lab to Native Populations in the Field JF - Frontiers in Plant Science N2 - Experimental high-throughput analysis of molecular networks is a central approach to characterize the adaptation of plant metabolism to the environment. However, recent studies have demonstrated that it is hardly possible to predict in situ metabolic phenotypes from experiments under controlled conditions, such as growth chambers or greenhouses. This is particularly due to the high molecular variance of in situ samples induced by environmental fluctuations. An approach of functional metabolome interpretation of field samples would be desirable in order to be able to identify and trace back the impact of environmental changes on plant metabolism. To test the applicability of metabolomics studies for a characterization of plant populations in the field, we have identified and analyzed in situ samples of nearby grown natural populations of Arabidopsis thaliana in Austria. A. thaliana is the primary molecular biological model system in plant biology with one of the best functionally annotated genomes representing a reference system for all other plant genome projects. The genomes of these novel natural populations were sequenced and phylogenetically compared to a comprehensive genome database of A. thaliana ecotypes. Experimental results on primary and secondary metabolite profiling and genotypic variation were functionally integrated by a data mining strategy, which combines statistical output of metabolomics data with genome-derived biochemical pathway reconstruction and metabolic modeling. Correlations of biochemical model predictions and population-specific genetic variation indicated varying strategies of metabolic regulation on a population level which enabled the direct comparison, differentiation, and prediction of metabolic adaptation of the same species to different habitats. These differences were most pronounced at organic and amino acid metabolism as well as at the interface of primary and secondary metabolism and allowed for the direct classification of population-specific metabolic phenotypes within geographically contiguous sampling sites. KW - eco-metabolomics KW - in situ analysis KW - metabolomics KW - metabolic modeling KW - SNP KW - natural variation KW - Jacobian matrix KW - green systems biology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189560 SN - 1664-462X VL - 9 IS - 1556 ER - TY - INPR A1 - Werner, Rudolf A. A1 - Bundschuh, Ralph A. A1 - Bundschuh, Lena A1 - Javadi, Mehrbod S. A1 - Leal, Jeffrey P. A1 - Higuchi, Takahiro A1 - Pienta, Kenneth J. A1 - Buck, Andreas K. A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Lapa, Constantin A1 - Rowe, Steven P. T1 - Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging T2 - Journal of Nuclear Medicine N2 - Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center. Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed. Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4%) instances, three readers in 40/125 (32%) and two observers in 27/125 (21.6%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005). Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials. KW - 18F-DCFPyL KW - Positronen-Emissions-Tomografie KW - PSMA-RADS KW - interreader KW - interobserver KW - PSMA KW - prostate cancer KW - RADS KW - reporting and data system KW - PET Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167788 SN - 0161-5505 N1 - This research was originally published in JNM. Rudolf A. Werner, Ralph A. Bundschuh, Lena Bundschuh, Mehrbod S. Javadi, Jeffrey P. Leal, Takahiro Higuchi, Kenneth J. Pienta, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Constantin Lapa and Steven P. Rowe. Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on 18F-DCFPyL PET/CT Imaging. J Nucl Med 2018;59:1857-1864 © SNMMI. ER - TY - JOUR A1 - Chtourou, Hamdi A1 - Engel, Florian Azad A1 - Fakhfakh, Hassen A1 - Fakhfakh, Hazem A1 - Hammouda, Omar A1 - Ammar, Achraf A1 - Trabelsi, Khaled A1 - Souissi, Nizar A1 - Sperlich, Billy T1 - Diurnal Variation of Short-Term Repetitive Maximal Performance and Psychological Variables in Elite Judo Athletes JF - Frontiers in Physiology N2 - Objectives: The aim of this study was to examine the effect of time of day on short-term repetitive maximal performance and psychological variables in elite judo athletes. Methods: Fourteen Tunisian elite male judokas (age: 21 ± 1 years, height:172 ± 7 cm, body-mass: 70.0 ± 8.1 kg) performed a repeated shuttle sprint and jump ability (RSSJA) test (6 m × 2 m × 12.5 m every 25-s incorporating one countermovement jump (CMJ) between sprints) in the morning (7:00 a.m.) and afternoon (5:00 p.m.). Psychological variables (Profile of mood states (POMS-f) and Hooper questionnaires) were assessed before and ratings of perceived exertion (RPE) immediately after the RSSJA. Results: Sprint times (p > 0.05) of the six repetition, fatigue index of sprints (p > 0.05) as well as mean (p > 0.05) jump height and fatigue index (p > 0.05) of CMJ did not differ between morning and afternoon. No differences were observed between the two times-of-day for anxiety, anger, confusion, depression, fatigue, interpersonal relationship, sleep, and muscle soreness (p > 0.05). Jump height in CMJ 3 and 4 (p < 0.05) and RPE (p < 0.05) and vigor (p < 0.01) scores were higher in the afternoon compared to the morning. Stress was higher in the morning compared to the afternoon (p < 0.01). Conclusion: In contrast to previous research, repeated sprint running performance and mood states of the tested elite athletes showed no-strong dependency of time-of-day of testing. A possible explanation can be the habituation of the judo athletes to work out early in the morning. KW - circadian rhythm KW - repeated sprint running KW - repeated exercise KW - mood KW - fatigue Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189269 SN - 1664-042X VL - 9 ER - TY - JOUR A1 - Akhrif, Atae A1 - Romanos, Marcel A1 - Domschke, Katharina A1 - Schmitt-Boehrer, Angelika A1 - Neufang, Susanne T1 - Fractal Analysis of BOLD Time Series in a Network Associated With Waiting Impulsivity JF - Frontiers in Physiology N2 - Fractal phenomena can be found in numerous scientific areas including neuroscience. Fractals are structures, in which the whole has the same shape as its parts. A specific structure known as pink noise (also called fractal or 1/f noise) is one key fractal manifestation, exhibits both stability and adaptability, and can be addressed via the Hurst exponent (H). FMRI studies using H on regional fMRI time courses used fractality as an important characteristic to unravel neural networks from artificial noise. In this fMRI-study, we examined 103 healthy male students at rest and while performing the 5-choice serial reaction time task. We addressed fractality in a network associated with waiting impulsivity using the adaptive fractal analysis (AFA) approach to determine H. We revealed the fractal nature of the impulsivity network. Furthermore, fractality was influenced by individual impulsivity in terms of decreasing fractality with higher impulsivity in regions of top-down control (left middle frontal gyrus) as well as reward processing (nucleus accumbens and anterior cingulate cortex). We conclude that fractality as determined via H is a promising marker to quantify deviations in network functions at an early stage and, thus, to be able to inform preventive interventions before the manifestation of a disorder. KW - fMRI KW - Hurst Exponent KW - frontal cortex KW - nucleus accumbens KW - biomarker KW - impulse control disorders Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189191 SN - 1664-042X VL - 9 ER - TY - JOUR A1 - Engel, Florian Azad A1 - Ackermann, Alexander A1 - Chtourou, Hamdi A1 - Sperlich, Billy T1 - High-Intensity Interval Training Performed by Young Athletes: A Systematic Review and Meta-Analysis JF - Frontiers in Physiology N2 - Background: High-intensity interval training (HIIT) is as a time-efficient alternative to moderate- or low-intensity continuous exercise for improving variables related to endurance and anaerobic performance in young and adolescent athletes. Objectives: To assess original research about enhancement of endurance and anaerobic exercise performance in young and adolescent athletes performing HIIT. Method: Relevant articles published in peer-reviewed journals were retrieved from the electronic databases PubMed and SPORTDiscus in December 2017. Inclusion criteria were: (i) controlled trials (HIIT vs. alternative training protocol) with pre-post design; (ii) healthy young athletes (≤18 years); (iii) assessing variables related to endurance and exercise performance. Hedges' g effect size (ES), and associated 95% confidence intervals were calculated for comparison of any outcome between experimental (HIIT) and alternative training protocol. Results: Twenty four studies, involving 577 athletes (mean age: 15.5 ± 2.2 years), were included in this review. HIIT exerted no or small positive mean ES on peak oxygen uptake (VO2peak), running performance, repeated sprint ability, jumping performance and submaximal heart rate. Although the mean ES for changes in VO2peak with HIIT is small (mean g = 0.10±0.28), the average increase in VO2peak from pre to post HIIT-interventions were 7.2 ± 6.9% vs. 4.3 ± 6.9% with any other alternative intervention. HIIT largely and positively affected running speed and oxygen consumption at various lactate- or ventilatory-based thresholds, as well as for sprint running performance. Calculations showed negative mean ES for change-of-direction ability (large), and peak blood lactate concentrations (small). Mean duration per training session for HIIT was shorter than for control interventions (28 ± 15 min vs. 38 ± 24 min). Conclusion: The present findings suggest that young athletes performing HIIT may improve certain important variables related to aerobic, as well as anaerobic, performance. With HIIT, most variables related to endurance improved to a higher extent, compared to alternative training protocols. However, based on ES, HIIT did not show clear superiority to the alternative training protocols. Nevertheless, young athletes may benefit from HIIT as it requires less time per training session leaving more time for training sport specific skills. KW - adolescents KW - physical fitness KW - aerobic training KW - peak oxygen uptake KW - training intensity Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189173 SN - 1664-042X VL - 9 ER - TY - JOUR A1 - Fuss, Franz Konstantin A1 - Düking, Peter A1 - Weizman, Yehuda T1 - Discovery of a Sweet Spot on the Foot with a Smart Wearable Soccer Boot Sensor That Maximizes the Chances of Scoring a Curved Kick in Soccer JF - Frontiers in Physiology N2 - This paper provides the evidence of a sweet spot on the boot/foot as well as the method for detecting it with a wearable pressure sensitive device. This study confirmed the hypothesized existence of sweet and dead spots on a soccer boot or foot when kicking a ball. For a stationary curved kick, kicking the ball at the sweet spot maximized the probability of scoring a goal (58–86%), whereas having the impact point at the dead zone minimized the probability (11–22%). The sweet spot was found based on hypothesized favorable parameter ranges (center of pressure in x/y-directions and/or peak impact force) and the dead zone based on hypothesized unfavorable parameter ranges. The sweet spot was rather concentrated, independent of which parameter combination was used (two- or three-parameter combination), whereas the dead zone, located 21 mm from the sweet spot, was more widespread. KW - smart soccer boot KW - pressure sensor KW - sweet spot KW - dead spot KW - probability of scoring a goal KW - center of pressure KW - impact force KW - wearable technology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189126 SN - 1664-042X VL - 9 ER - TY - THES A1 - Gil Pulido, Jesús T1 - The role of Batf3-dependent dendritic cells and the IL-23 receptor in atherosclerosis T1 - Die Rolle von Batf3-abhängigen dendritischen Zellen und des IL-23-Rezeptors in der Atherosklerose N2 - Cardiovascular diseases represent the leading cause of death worldwide, with myocardial infarction and strokes being the most common complications. In both cases, the appearance of an enlarged artery wall as a consequence of a growing plaque is responsible for the disturbance of the blood flow. The formation of plaques is driven by a chronic inflammatory condition known as atherosclerosis, characterized by an initial step of endothelial cell (EC) dysfunction followed by the recruitment of circulating immune cells into the tunica intima of the vessel. Accumulation of lipids and cells lead to the formation of atheromatous plaques that will define the cardiovascular outcome of an individual. The role of the immune system in the progression of atherosclerosis has been widely recognized. By far, macrophages constitute the most abundant cell type in lesions and are known to be the major source of the lipid-laden foam cell pool during the course of the disease. However, other immune cells types, including T cells, dendritic cells (DCs) or mast cells, among others, have been described to be present in human and mouse plaques. How these populations can modulate the atherogenic process is dependent on their specialized function. DCs constitute a unique population with the ability to bridge innate and adaptive immune responses, mainly by their strong capacity to present antigens bound to a major histocompatibility complex (MHC) molecule. Given their ability to polarize T cells and secrete cytokines, their role in atherosclerosis has gained attention for the development of new therapeutic approaches that could impact lesion growth. Hence, knowing the effect of a specific subset is an initial key step to evaluate its potential for clinical purposes. For example, the basic leucine zipper ATF-like 3 transcription factor (Batf3) controls the development of conventional dendritic cells type 1 (cDCs1), characterized by the expression of the surface markers CD8 and CD103. Initially, they were described to promote both T-helper 1 (Th1) and regulatory T cell (Treg) responses, known to accelerate and to protect against atherosclerosis, respectively. The first part of this thesis aimed to elucidate the potential role of Batf3-dependent DCs in atherosclerosis and concluded that even though systemic immune responses were mildly altered they do not modify the course of the disease and may not represent an attractive candidate for clinical studies. DCs also have the ability to impact lesion growth through the release of a broad range of cytokines, which can either directly impact atherosclerotic plaques by modulating resident cells, or by further polarizing T cell responses. Among others, interleukin (IL) 23, a member of the IL-12 family of cytokines, has received much attention during the past year due to its connection to autoimmunity. IL-23 is known to induce pathogenicity of Th17 cells and is responsible for the development of several autoimmune diseases including multiple sclerosis, psoriasis or rheumatoid arthritis. Interestingly, these patients often present with an accelerated course of atherosclerosis and thus, are at higher risk of developing cardiovascular events. Several epidemiological studies have pointed toward a possible connection between IL-23 and its receptor IL-23R in atherosclerosis, although their exact contribution remains to be elucidated. The second part of this thesis showed that resident antigen-presenting cells (APCs) in the aorta produced IL-23 during the steady state but this secretion was greatly enhanced after incubation with oxidized low-density lipoprotein (oxLDL). Furthermore, disruption of the IL-23R signaling led to decreased relative necrotic plaque area in lesions of Ldlr-/-Il23r-/- mice fed a high-fat diet (HFD) for 6 and 12 weeks compared to Ldlr-/- controls. A proposed mechanism involves that increased IL-23 production in the context of atherosclerosis may promote the pathogenicity of IL-23-responding T cells, especially IL-23R+ γδ T cells in the aortic root. Response to IL-23 might increase the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17 and alter the pro- and anti-inflammatory balance of cytokines in the aortic root. Altogether, these data showed that the IL-23 / IL-23R axis play a role in plaque stability. N2 - Kardiovaskuläre Erkrankungen sind weltweit die häufigste Todesursache, wobei Myokardinfarkt und Schlaganfall die häufigsten Komplikationen darstellen. In beiden Fällen ist das Auftreten einer verbreiterten Arterienwand als Folge eines wachsenden Plaques für die Störung des Blutflusses verantwortlich. Die Bildung von Plaques wird durch einen chronischen Entzündungszustand, bekannt als Atherosklerose, ausgelöst. Zunächst kommt es dabei zur Entstehung einer endothelialen Dysfunktion, die zur Rekrutierung zirkulierender Immunzellen in die Tunica Intima des Gefäßes führt. Die Akkumulation von Lipiden und Zellen wiederum führt zur Bildung von atheromatösen Plaques, die den kardiovaskulären Gefäßstatus eines Individuums bestimmen. Die Rolle des Immunsystems bei der Progression der Atherosklerose wurde weithin anerkannt. Makrophagen stellen bei weitem den häufigsten Zelltyp innerhalb der Läsionen dar und sind bekanntermaßen die Hauptquelle des mit Lipid beladenen Schaumzellpools im Verlauf der Erkrankung. Es wurde jedoch auch beschrieben, dass andere Arten von Immunzellen, einschließlich der T-Zellen, dendritischen Zellen (DCs) und Mastzellen, in humanen und murinen Plaques vorhanden sind. Wie diese Populationen den atherogenen Prozess modulieren können, hängt von ihrer spezialisierten Funktion ab. DCs bilden eine einzigartige Population, der es möglich ist, angeborene und adaptive Immunartworten zu überbrücken. Dies geschieht hauptsächlich aufgrund ihrer ausgeprägten Fähigkeit, Antigene zu präsentieren, die an einen Haupthistokompatibilitätskomplex gebunden sind. Angesichts ihrer Rolle in der Polarisierung von T-Zellen und der Sezernierung von Zytokinen haben sie bisher Aufmerksamkeit bei der Entwicklung neuer therapeutischer Ansätze zur Beeinflussung des Läsionswachstums erlangt. Die Kenntnis der Wirkung einer bestimmten Subpopulation ist ein erster wichtiger Schritt, um ihr Potenzial für klinische Zwecke zu bewerten. Zum Beispiel steuert der Transkriptionsfaktor „basic leucine zipper ATF-like 3“ (Batf3) die Entwicklung von herkömmlichen dendritischen Zellen Typ 1, welche durch die Expression der Oberflächenmarker CD8 und CD103 gekennzeichnet sind. Anfänglich wurde beschrieben, dass sie sowohl die Antworten von T-Helfer 1 als auch von regulatorischen T-Zellen fördern, welche je nach Zellfunktion die Atherosklerose beschleunigen oder vorbeugen. Im ersten Teil dieser Arbeit wurde die potentielle Rolle von Batf3-abhängigen DCs für die Entstehung der Atherosklerose aufgeklärt. Trotz diese einer leichten Veränderungen der systemischen Immunantwort den Krankheitsverlauf nicht beeinflussen und daher keine attraktiven Kandidaten für klinische Studien darstellen. DCs haben auch die Fähigkeit das Läsionswachstum durch Freisetzung einer breiten Palette an Zytokinen zu beeinflussen, die atherosklerotische Plaques entweder direkt durch Modulation von ortsständigen residenten Zellen oder durch weiteres Polarisieren von T-Zell-Reaktionen beeinflussen können. Unter anderem hat interleukin (IL) 23, ein Mitglied der IL-12-Zytokinfamilie, aufgrund seines Zusammenhangs mit Auto-immunität im vergangenen Jahr viel Aufmerksamkeit erhalten. Es ist bekannt, dass IL-23 die Pathogenität von Th17-Zellen induziert und für die Entwicklung von mehreren Autoimmunkrankheiten einschließlich multipler Sklerose, Psoriasis oder rheumatoider Arthritis verantwortlich ist. Interessanterweise haben alle diese Erkrankungen gemeinsam, dass sie die Entstehung einer Atherosklerose beschleunigen. Die betroffenen Patienten haben ein höheres Risiko für ein kardiovaskuläres Ereignis. Mehrere epidemiologische Studien haben auf einen möglichen Zusammenhang zwischen IL-23 und seinem Rezeptor IL-23R bei Atherosklerose hingewiesen, auch wenn die genaue Relevanz dieser Hinweise noch zu klären ist. Im zweiten Teil dieser Arbeit konnte es gezeigt werden, dass ortsständige antigenpräsentierende Zellen in der Aorta IL-23 zwar bereits im Steady State produzieren, diese Sekretion jedoch nach Inkubation mit oxLDL stark erhöht ist. Darüber hinaus führte eine Störung der IL-23R-Signalgebung nach 6 bis 12 Wochen einer fettreichen Diät (HFD) zu einer verringerten relativen nekrotischen Plaque-Fläche in Läsionen von Ldlr-/-Il23r-/- Mäusen verglichen mit Ldlr-/- Mäusen. In Bezug auf den zugrunde liegenden Mechanismus wurde diskutiert, dass eine erhöhte IL-23-Produktion im Zusammenhang mit Atherosklerose die Pathogenität von IL-23R-reaktiven T-Zellen, insbesondere von IL-23R+ γδ T-Zellen in der Aortenwurzel, fördern kann. Reaktionen auf IL-23 könnten die Freisetzung von Granulozyten-Monozyten-Kolonie-stimulierendem Faktor und IL-17 erhöhen und das pro- und antiinflammatorische Gleichgewicht von Zytokinen innerhalb der Aortenwurzel verändern. Insgesamt zeigen diese Daten, dass die IL-23 / IL-23R Achse eine wichtige Rolle in der Etablierung der Plaquestabilität einnimmt. KW - Arteriosklerose KW - Immunsystem KW - Dendritic cells KW - IL-23 KW - Interleukine KW - Dendritische Zelle KW - Atherosclerosis Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167203 ER - TY - INPR A1 - Yin, Yafu A1 - Werner, Rudolf A. A1 - Higuchi, Takahiro A1 - Lapa, Constantin A1 - Pienta, Kenneth J. A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Rowe, Steven P. T1 - Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMARADS- 3B Categories T2 - Journal of Nuclear Medicine N2 - Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa. Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy. Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0%) PSMA-RADS-3A lesions and 3/14 (21.4%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up. Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy. KW - PSMA-RADS-3B KW - Positronen-Emissions-Tomografie KW - prostate-specific membrane antigen KW - prostate cancer KW - PSMA-targeted PET KW - PSMA-RADS-3A Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167594 SN - 0161-5505 N1 - This research was originally published in JNM. Yafu Yin, Rudolf A. Werner, Takahiro Higuchi, Constantin Lapa, Kenneth J. Pienta, Martin G. Pomper, Michael A. Gorin, Steven P. Rowe. Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMA-RADS-3B Categories. J Nucl Med. 2019;60:511-516 © SNMMI. ER - TY - JOUR A1 - Schairer, Patrick A1 - Wagner, Stephan A1 - Geidel, Ekkehard T1 - An experimental introduction to basic principles of the interaction of electromagnetic radiation with matter JF - World Journal of Chemical Education N2 - To understand basic principles about the interaction of electromagnetic radiation with matter is often a challenge in chemical education due to the difficult theoretical background of this topic. The present contribution therefore offers an experimental based introduction into the basic principles of UV/Vis spectroscopy following a three-step strategy. The starting point is to construct a simple self-built spectrometer working within the visible range of light. Learners can explore the most important components of such a device and understand their functions without previous knowledge. In a second step, emission spectra of different common light sources are investigated and compared. Finally, spectroscopic experiments are suggested for chemical education such as the qualitative detection of cations and the quantitative analysis of the dye carmine in food. This context-based introduction links chemical applications with the everyday life. It can be presumed that this way, learners are provided an easier access to radiation-matter interaction. KW - UV/Vis spectroscopy KW - low-cost spectrometer KW - flame test KW - quantitative analysis KW - carmine Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175811 VL - 6 IS - 1 ER - TY - JOUR A1 - Grossheinrich, Nicola A1 - Firk, Christine A1 - Schulte-Rüther, Martin A1 - von Leupoldt, Andreas A1 - Konrad, Kerstin A1 - Huestegge, Lynn T1 - Looking while unhappy: a mood-congruent attention bias toward sad adult faces in children JF - Frontiers in Psychology N2 - A negative mood-congruent attention bias has been consistently observed, for example, in clinical studies on major depression. This bias is assumed to be dysfunctional in that it supports maintaining a sad mood, whereas a potentially adaptive role has largely been neglected. Previous experiments involving sad mood induction techniques found a negative mood-congruent attention bias specifically for young individuals, explained by an adaptive need for information transfer in the service of mood regulation. In the present study we investigated the attentional bias in typically developing children (aged 6–12 years) when happy and sad moods were induced. Crucially, we manipulated the age (adult vs. child) of the displayed pairs of facial expressions depicting sadness, anger, fear and happiness. The results indicate that sad children indeed exhibited a mood specific attention bias toward sad facial expressions. Additionally, this bias was more pronounced for adult faces. Results are discussed in the context of an information gain which should be stronger when looking at adult faces due to their more expansive life experience. These findings bear implications for both research methods and future interventions. KW - eye tracking KW - emotion regulation KW - mood induction KW - attention bias KW - major depression KW - adaptive role Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177688 VL - 9 IS - 2577 ER - TY - JOUR A1 - Rau, Monika A1 - Schmitt, Johannes A1 - Berg, Thomas A1 - Kremer, Andreas E. A1 - Stieger, Bruno A1 - Spanaus, Katharina A1 - Bengsch, Bertram A1 - Romero, Marta R. A1 - Marin, Jose J. A1 - Keitel, Verena A1 - Klinker, Hartwig A1 - Tony, Hans-Peter A1 - Müllhaupt, Beat A1 - Geier, Andreas T1 - Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients JF - PLoS ONE N2 - Background & aims Serum interferon-gamma-inducible protein-10 (IP-10) is elevated in cholestatic liver diseases and predicts response to antiviral therapy in patients with chronic hepatitis C virus (HCV) infection. Dipeptidylpeptidase 4 (DPPIV) cleaves active IP-10 into an inactive form, which inhibits recruitment of CXCR3+ T cells to the liver. In this study the link between IP-10 levels, DPPIV activity in serum and CXCR3+ T cells is analysed in cholestatic and non-cholestatic liver patients. Methods In serum DPPIV activity (by enzymatic assay), IP-10 (by ELISA) and bile acids (BA) (by enzymatic assay) were analysed in 229 naive HCV genotype (GT) 1 patients and in 16 patients with cholestatic liver disease. In a prospective follow-up (FU) cohort of 27 HCV GT 1 patients peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ cells were measured by FACS. Results In 229 HCV patients serum IP-10 levels correlated positively to DPPIV serum activity. Higher IP-10 levels and DPPIV activity were detected in cholestatic and in cirrhotic HCV patients. Increased IP-10 serum levels were associated with therapeutic non-response to antiviral treatment with pegylated-interferon and ribavirin. In the HCV FU cohort elevated IP-10 serum levels and increased BA were associated with higher frequencies of peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ T cells. Positive correlation between serum IP-10 levels and DPPIV activity was likewise validated in patients with cholestatic liver diseases. Conclusions A strong correlation between elevated serum levels of IP-10 and DPPIV activity was seen in different cholestatic patient groups. Furthermore, in cholestatic HCV patients a functional link to increased numbers of peripheral CXCR3+ immune cells could be observed. The source of DPPIV release in cholestatic patients remains open. KW - hepatitis C virus KW - T cells KW - liver diseases KW - chemokines KW - cytotoxic T cells KW - immune cells KW - cirrhosis KW - bile Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177674 VL - 13 IS - 12 ER - TY - JOUR A1 - Rodrigues, Johannes A1 - Nagowski, Natalie A1 - Mussel, Patrick A1 - Hewig, Johannes T1 - Altruistic punishment is connected to trait anger, not trait altruism, if compensation is available JF - Heliyon N2 - 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. KW - psychology KW - altruism KW - altruistic punishment KW - altruistic compensation KW - anger Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177669 VL - 4 IS - 11 ER - TY - JOUR A1 - Pfister, Roland A1 - Schwarz, Katharina A. T1 - Should we pre-date the beginning of scientific psychology to 1787? JF - Frontiers in Psychology N2 - No abstract available. KW - psychology KW - history Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177641 VL - 9 IS - 2481 ER - TY - JOUR A1 - Keller, Alexander A1 - Brandel, Annette A1 - Becker, Mira C. A1 - Balles, Rebecca A1 - Abdelmohsen, Usama Ramadan A1 - Ankenbrand, Markus J. A1 - Sickel, Wiebke T1 - Wild bees and their nests host Paenibacillus bacteria with functional potential of avail JF - Microbiome N2 - 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. KW - 16S metabarcoding KW - American foulbrood KW - anti-microbial activit KW - bacterial genomics KW - bioassays KW - European foulbrood KW - Paenibacterin KW - phylogenomics KW - bee disease KW - pathogen vector Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177554 VL - 6 IS - 229 ER - TY - JOUR A1 - Feldheim, Jonas A1 - Kessler, Almuth F A1 - Schmitt, Dominik A1 - Wilczek, Lara A1 - Linsenmann, Thomas A1 - Dahlmann, Mathias A1 - Monoranu, Camelia M A1 - Ernestus, Ralf-Ingo A1 - Hagemann, Carsten A1 - Löhr, Mario T1 - Expression of activating transcription factor 5 (ATF5) is increased in astrocytomas of different WHO grades and correlates with survival of glioblastoma patients JF - OncoTargets and Therapy N2 - 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. KW - glioblastoma multiforme KW - recurrence KW - growth pattern KW - protein and mRNA expression Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177541 VL - 11 ER - TY - JOUR A1 - Ruedenauer, Fabian A. A1 - Wöhrle, Christine A1 - Spaethe, Johannes A1 - Leonhardt, Sara D. T1 - Do honeybees (Apis mellifera) differentiate between different pollen types? JF - PLoS ONE N2 - 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. KW - pollen KW - bees KW - honey bees KW - conditioned response KW - behavioral conditioning KW - foraging KW - nutrients KW - sensory cues Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177537 VL - 13 IS - 11 ER - TY - JOUR A1 - Beck, Sebastian A1 - Yu-Strzelczyk, Jing A1 - Pauls, Dennis A1 - Constantin, Oana M. A1 - Gee, Christine E. A1 - Ehmann, Nadine A1 - Kittel, Robert J. A1 - Nagel, Georg A1 - Gao, Shiqiang T1 - Synthetic light-activated ion channels for optogenetic activation and inhibition JF - Frontiers in Neuroscience N2 - 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. KW - optogenetics KW - calcium KW - potassium KW - bPAC KW - CNG channel KW - cAMP KW - Drosophila melanogaster motoneuron KW - rat hippocampal neurons Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177520 VL - 12 IS - 643 ER - TY - JOUR A1 - Tian, Yuehui A1 - Gao, Shiqiang A1 - von der Heyde, Eva Laura A1 - Hallmann, Armin A1 - Nagel, Georg T1 - Two-component cyclase opsins of green algae are ATP-dependent and light-inhibited guanylyl cyclases JF - BMC Biology N2 - 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. KW - chlamydomonas reinhardtii KW - volvox carteri KW - two-component system KW - chlamyopsin KW - optogenetics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177516 VL - 16 IS - 144 ER - TY - JOUR A1 - Strohmeier, Michael A1 - Walter, Thomas A1 - Rothe, Julian A1 - Montenegro, Sergio T1 - Ultra-wideband based pose estimation for small unmanned aerial vehicles JF - IEEE Access N2 - 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°. KW - UAV KW - navigation KW - pose estimation KW - distance measurement KW - DecaWave KW - extended Kalman filter KW - UWB Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177503 VL - 6 ER - TY - JOUR A1 - Lotz, C. A1 - Kiesewetter, L. A1 - Schmid, F. F. A1 - Hansmann, J. A1 - Walles, H. A1 - Groeber-Becker, F. T1 - Replacing the Draize eye test: impedance spectroscopy as a 3R method to discriminate between all GHS categories for eye irritation JF - Scientific Reports N2 - 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. KW - biological models KW - electrical and electronic engineering KW - regenerative medicine KW - tissue engineering KW - toxicology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177492 VL - 8 IS - 15049 ER - TY - JOUR A1 - Haring, Bernhard A1 - Selvin, Elizabeth A1 - He, Xintong A1 - Coresh, Josef A1 - Steffen, Lyn M. A1 - Folsom, Aaron R. A1 - Tang, Weihong A1 - Rebholz, Casey M. T1 - Adherence to the dietary approaches to stop hypertension dietary pattern and risk of abdominal aortic aneurysm: results from the ARIC study JF - Journal of the American Heart Association N2 - 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. KW - diet KW - dietary approaches to stop hypertension KW - aneurysm Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177442 VL - 7 IS - 21 ER - TY - JOUR A1 - Boelch, Sebastian P. A1 - Rueckl, Kilian A1 - Fuchs, Clara A1 - Jordan, Martin A1 - Knauer, Markus A1 - Steinert, Andre A1 - Rudert, Maximilian A1 - Luedemann, Martin T1 - 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 JF - BioMed Research International N2 - 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. KW - Copal\(^®\) spacem KW - PMMA bone cement KW - elution KW - compressive strength Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177435 VL - 2018 IS - 4323518 ER - TY - JOUR A1 - Pauls, Dennis A1 - Blechschmidt, Christine A1 - Frantzmann, Felix A1 - el Jundi, Basil A1 - Selcho, Mareike T1 - A comprehensive anatomical map of the peripheral octopaminergic/tyraminergic system of Drosophila melanogaster JF - Scientific Reports N2 - 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. KW - neural circuits KW - peripheral nervous system KW - Drosophila melanogaster Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177412 VL - 8 IS - 15314 ER - TY - JOUR A1 - Ruf, Katharina A1 - Wirbelauer, Johannes A1 - Beissert, Antje A1 - Frieauff, Eric T1 - Successful treatment of severe arterial hypotension and anuria in a preterm infant with renal tubular dysgenesis– a case report JF - Maternal Health, Neonatology and Perinatology N2 - 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. KW - potter sequence KW - oligohydramnios sequence KW - renal tubular dysgenesis KW - arterial hypotension KW - vasopressin KW - respiratory distress KW - anuria KW - preterm KW - dry lung syndrome KW - neonatal renal failure Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177405 VL - 4 IS - 27 ER - TY - JOUR A1 - Bakhtiarizadeh, Mohammad Reza A1 - Hosseinpour, Batool A1 - Shahhoseini, Maryam A1 - Korte, Arthur A1 - Gifani, Peyman T1 - Weighted gene co-expression network analysis of endometriosis and identification of functional modules associated with its main hallmarks JF - Frontiers in Genetics N2 - 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. KW - endometriosis KW - module KW - weighted gene co-expression network KW - hub genes KW - expression Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177376 VL - 9 IS - 453 ER - TY - JOUR A1 - Weigel, Tobias A1 - Schmitz, Tobias A1 - Pfister, Tobias A1 - Gaetzner, Sabine A1 - Jannasch, Maren A1 - Al-Hijailan, Reem A1 - Schürlein, Sebastian A1 - Suliman, Salwa A1 - Mustafa, Kamal A1 - Hansmann, Jan T1 - A three-dimensional hybrid pacemaker electrode seamlessly integrates into engineered, functional human cardiac tissue in vitro JF - Scientific Reports N2 - 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. KW - biomedical materials KW - cardiac device therapy KW - hybrid pacemaker Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177368 VL - 8 IS - 14545 ER - TY - JOUR A1 - Schliermann, Anna A1 - Nickel, Joachim T1 - Unraveling the connection between fibroblast growth factor and bone morphogenetic protein signaling JF - International Journal of Molecular Sciences N2 - 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. KW - bone morphogenetic protein KW - fibroblast growth factor KW - signal transduction KW - cross-talk KW - signal integration Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177358 SN - 1422-0067 VL - 19 IS - 10 ER - TY - JOUR A1 - Malsch, Carolin A1 - Liman, Thomas A1 - Wiedmann, Silke A1 - Siegerink, Bob A1 - Georgakis, Marios K. A1 - Tiedt, Steffen A1 - Endres, Matthias A1 - Heuschmann, Peter U. T1 - Outcome after stroke attributable to baseline factors—the PROSpective Cohort with Incident Stroke (PROSCIS) JF - PLoS ONE N2 - 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. KW - ischemic stroke KW - stroke KW - physical activity KW - diabetes mellitus KW - regression analysis KW - hemorrhagic stroke KW - atrial fibrillation KW - hypertension Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177342 VL - 13 IS - 9 ER - TY - JOUR A1 - Jarick, Marcel A1 - Bertsche, Ute A1 - Stahl, Mark A1 - Schultz, Daniel A1 - Methling, Karen A1 - Lalk, Michael A1 - Stigloher, Christian A1 - Steger, Mirco A1 - Schlosser, Andreas A1 - Ohlsen, Knut T1 - The serine/threonine kinase Stk and the phosphatase Stp regulate cell wall synthesis in Staphylococcus aureus JF - Scientific Reports N2 - 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. KW - bacterial transcription KW - pathogens KW - cell wall synthesis Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177333 VL - 8 IS - 13693 ER - TY - JOUR A1 - Sperlich, Billy A1 - De Clerck, Ine A1 - Zinner, Christoph A1 - Holmberg,, Hans-Christer A1 - Wallmann-Sperlich, Birgit T1 - Prolonged sitting interrupted by 6-min of high-intensity exercise: circulatory, metabolic, hormonal, thermal, cognitive, and perceptual responses JF - Frontiers in Physiology N2 - 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. KW - inactivity KW - high-intensity interval training KW - sedentary lifestyle KW - students KW - workplace KW - intervention KW - physical activity KW - health promotion Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177307 VL - 9 IS - 1279 ER - TY - JOUR A1 - Krishna, Anand A1 - Peter, Sebastian M. T1 - Questionable research practices in student final theses – prevalence, attitudes, and the role of the supervisor’s perceived attitudes JF - PLoS ONE N2 - 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. KW - supervisors KW - psychology KW - human learning KW - learning KW - careers KW - scientists KW - psychometrics KW - psychologists Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177296 VL - 13 IS - 8 ER - TY - JOUR A1 - Grimm, Johannes A1 - Hufnagel, Anita A1 - Wobser, Marion A1 - Borst, Andreas A1 - Haferkamp, Sebastian A1 - Houben, Roland A1 - Meierjohann, Svenja T1 - BRAF inhibition causes resilience of melanoma cell lines by inducing the secretion of FGF1 JF - Oncogenesis N2 - 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. KW - melanoma KW - senescence KW - BRAF KW - tumor Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177261 VL - 7 IS - 71 ER - TY - JOUR A1 - Abdelhafez, Omnia Hesham A1 - Fawzy, Michael Atef A1 - Fahim, John Refaat A1 - Desoukey, Samar Yehia A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Abdelmohsen, Usama Ramadan T1 - Hepatoprotective potential of Malvaviscus arboreus against carbon tetrachloride-induced liver injury in rats JF - PLoS ONE N2 - 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. KW - high performance liquid chromatography KW - phenols KW - phytochemicals KW - antioxidants KW - metabolomics KW - medicinal plants KW - Egypt KW - xenobiotic metabolism KW - Malvaviscus arboreus Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177243 VL - 13 IS - 8 ER - TY - JOUR A1 - Kaluza, Benjamin F. A1 - Wallace, Helen M. A1 - Heard, Tim A. A1 - Minden, Vanessa A1 - Klein, Alexandra A1 - Leonhardt, Sara D. T1 - Social bees are fitter in more biodiverse environments JF - Scientific Reports N2 - 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. KW - biodiversity KW - ecosystem services KW - social bees KW - fitness Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177231 VL - 8 IS - 12353 ER - TY - JOUR A1 - Kienle-Garrido, Melina-Lorén A1 - Breitenbach, Tim A1 - Chudej, Kurt A1 - Borzì, Alfio T1 - Modeling and numerical solution of a cancer therapy optimal control problem JF - Applied Mathematics N2 - 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. KW - cancer KW - therapy KW - optimal control problem Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177152 VL - 9 IS - 8 ER - TY - JOUR A1 - Hefner, Jochen A1 - Berberich, Sara A1 - Lanvers, Elena A1 - Sanning, Maria A1 - Steimer, Ann-Kathrin A1 - Kunzmann, Volker T1 - Patient-doctor relationship and adherence to capecitabine in outpatients of a German comprehensive cancer center JF - Patient Preference and Adherence N2 - 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. KW - oral anticancer drugs KW - patient-doctor-relationship KW - capecitabine Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177143 VL - 12 ER - TY - JOUR A1 - Förstner, Konrad U A1 - Reuscher, Carina M A1 - Haberzettl, Kerstin A1 - Weber, Lennart A1 - Klug, Gabriele T1 - RNase E cleavage shapes the transcriptome of Rhodobacter sphaeroides and strongly impacts phototrophic growth JF - Life Science Alliance N2 - 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. KW - Rhodobacter sphaeroides KW - phototrophic growth KW - RNase E Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177139 VL - 1 IS - 4 ER - TY - JOUR A1 - Zoltner, Martin A1 - Krienitz, Nina A1 - Field, Mark C. A1 - Kramer, Susanne T1 - Comparative proteomics of the two T. brucei PABPs suggests that PABP2 controls bulk mRNA JF - PLoS Neglected Tropical Diseases N2 - 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. KW - Trypanosoma KW - mRNA KW - T. brucei KW - PABPs Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177126 VL - 12 IS - 7 ER - TY - JOUR A1 - Yu, Sung-Huan A1 - Vogel, Jörg A1 - Förstner, Konrad U. T1 - ANNOgesic: a Swiss army knife for the RNA-seq based annotation of bacterial/archaeal genomes JF - GigaScience N2 - 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/. KW - genome annotation KW - RNA-seq KW - transcriptomics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-178942 VL - 7 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Marcus, Charles A1 - Sheikhbahaei, Sara A1 - Solnes, Lilja B. A1 - Leal, Jeffrey P. A1 - Du, Yong A1 - Rowe, Steven P. A1 - Higuchi, Takahiro A1 - Buck, Andreas K. A1 - Lapa, Constantin A1 - Javadi, Mehrbod S. T1 - Visual and Semiquantitative Accuracy in Clinical Baseline 123I-Ioflupane SPECT/CT Imaging JF - Clinical Nuclear Medicine N2 - 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. KW - Single-Photon-Emissions-Computertomographie KW - SPECT KW - Parkinson’s disease KW - Parkinsonism KW - DaTscan KW - 123I-Ioflupane KW - SPECT KW - SPECT/CT Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168181 SN - 1536-0229 VL - 44 IS - 1 ER - TY - JOUR A1 - Redlich, Sarah A1 - Martin, Emily A. A1 - Wende, Beate A1 - Steffan-Dewenter, Ingolf T1 - Landscape heterogeneity rather than crop diversity mediates bird diversity in agricultural landscapes JF - PLoS ONE N2 - 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. KW - bird diversity KW - crop diversity KW - landscape heterogeneity Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177110 VL - 13 IS - 8 ER - TY - JOUR A1 - Bankoglu, Ezgi Eyluel A1 - Arnold, Charlotte A1 - Hering, Ilona A1 - Hankir, Mohammed A1 - Seyfried, Florian A1 - Stopper, Helga T1 - Decreased chromosomal damage in lymphocytes of obese patients after bariatric surgery JF - Scientific Reports N2 - 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. KW - obesity KW - bariatric surgery KW - cancer risk Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177090 VL - 8 IS - 11195 ER - TY - INPR A1 - Stennett, Tom A1 - Mattock, James A1 - Pentecost, Leanne A1 - Vargas, Alfredo A1 - Braunschweig, Holger T1 - Chelated Diborenes and their Inverse-Electron-Demand Diels- Alder Reactions with Dienes T2 - Angewandte Chemie, International Edition N2 - 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. KW - boron KW - cycloaddition KW - DFT calculations KW - chelates KW - low-valent compounds Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-178268 N1 - This is the pre-peer reviewed version of the following article: T. E. Stennett, J. D. Mattock, L. Pentecost, A. Vargas, H. Braunschweig, Angew. Chem. Int. Ed. 2018, 57, 15276., which has been published in final form at https://doi.org/10.1002/anie.201809217. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. ER - TY - INPR A1 - Stennett, Tom A1 - Bertermann, Rüdiger A1 - Braunschweig, Holger T1 - Construction of Linear and Branched Tetraboranes via 1,1- and 1,2-Diboration of Diborenes T2 - Angewandte Chemie, International Edition N2 - 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. KW - boron KW - diboration KW - chain structures KW - low-valent compounds KW - isomers Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-178276 N1 - This is the pre-peer reviewed version of the following article: T. E. Stennett, R. Bertermann, H. Braunschweig, Angew. Chem. Int. Ed. 2018, 57, 15896., which has been published in final form at https://doi.org/10.1002/anie.201809976. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. ER - TY - JOUR A1 - Schlichting, Matthias A1 - Rieger, Dirk A1 - Cusumano, Paola A1 - Grebler, Rudi A1 - Costa, Rodolfo A1 - Mazzotta, Gabriella M. A1 - Helfrich-Förster, Charlotte T1 - Cryptochrome interacts with actin and enhances eye-mediated light sensitivity of the circadian clock in Drosophila melanogaster JF - Frontiers in Molecular Neuroscience N2 - 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. KW - Drosophila melanogaster KW - cryptochrome KW - F-actin KW - phototransduction KW - activity rhythms Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177086 VL - 11 IS - 238 ER - TY - JOUR A1 - Kunze, Ekkehard A1 - Lilla, Nadine A1 - Stetter, Christian A1 - Ernestus, Ralf-Ingo A1 - Westermaier, Thomas T1 - Magnesium protects in episodes of critical perfusion after aneurysmal SAH JF - Translational Neuroscience N2 - 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. KW - subarachnoid hemorrhage KW - magnesium KW - neuroprotection KW - delayed cerebral infarction Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177078 VL - 9 IS - 1 ER - TY - JOUR A1 - Rasheed, Huma A1 - Höllein, Ludwig A1 - Holzgrabe, Ulrike T1 - Future information technology tools for fighting substandard and falsified medicines in low- and middle-income countries JF - Frontiers in Pharmacology N2 - 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. KW - track and trace KW - information technology KW - medicine authentication tools KW - mobile apps KW - quality evaluation KW - field testing KW - substandard and falsified medicines Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177068 VL - 9 IS - 995 ER - TY - JOUR A1 - Wurmb, T A1 - Schorscher, N A1 - Justice, P A1 - Dietz, S A1 - Schua, R A1 - Jarausch, T A1 - Kinstle, U A1 - Greiner, J A1 - Möldner, G A1 - Müller, J A1 - Kraus, M A1 - Simon, S A1 - Wagenhäuser, U A1 - Hemm, J A1 - Roewer, N A1 - Helm, M T1 - Structured analysis, evaluation and report of the emergency response to a terrorist attack in Wuerzburg, Germany using a new template of standardised quality indicators JF - Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine N2 - 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. KW - terror attack KW - mass casualties KW - evaluation KW - quality indicators KW - rescue mission Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177054 VL - 26 IS - 87 ER - TY - JOUR A1 - Fischer, Matthias A1 - Heinrichs, Harald T1 - Dimensions, dialectic, discourse. Three political perspectives on the sustainability of the German healthcare system JF - International Journal of Environmental Research and Public Health N2 - 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. KW - sustainability KW - German healthcare system KW - policy KW - politics KW - polity Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177003 VL - 15 IS - 7 ER - TY - JOUR A1 - Schuster, Frank A1 - Johannsen, Stephan A1 - Isbary, Susanne A1 - Türkmeneli, Ismail A1 - Roewer, Norbert T1 - In vitro effects of levosimendan on muscle of malignant hyperthermia susceptible and non-susceptible swine JF - BMC Anesthesiology N2 - 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. KW - malignant hyperthermia KW - levosimendan KW - muscle KW - pigs KW - in vitro contracture test Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176991 VL - 18 IS - 182 ER - TY - JOUR A1 - Boelch, S. P. A1 - Jakuscheit, A. A1 - Doerries, S. A1 - Fraissler, L. A1 - Hoberg, M. A1 - Arnholdt, J. A1 - Rudert, M. T1 - Periprosthetic infection is the major indication for TKA revision – experiences from a university referral arthroplasty center JF - BMC Musculoskeletal Disorders N2 - 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. KW - knee arthroplasty KW - revision KW - failure KW - periprosthetic infection Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176983 VL - 19 IS - 395 ER -