@article{BeckHovhanyanMenegazzietal.2018, author = {Beck, Katherina and Hovhanyan, Anna and Menegazzi, Pamela and Helfrich-F{\"o}rster, Charlotte and Raabe, Thomas}, title = {Drosophila RSK Influences the Pace of the Circadian Clock by Negative Regulation of Protein Kinase Shaggy Activity}, series = {Frontiers in Molecular Neuroscience}, volume = {11}, journal = {Frontiers in Molecular Neuroscience}, number = {122}, issn = {1662-5099}, doi = {10.3389/fnmol.2018.00122}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196034}, year = {2018}, abstract = {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.}, language = {en} } @article{LiDengXieetal.2018, author = {Li, Cong and Deng, Xiaobing and Xie, Xiaowen and Liu, Ying and Friedmann Angeli, Jos{\´e} Pedro and Lai, Luhua}, title = {Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy}, series = {Frontiers in Pharmacology}, volume = {9}, journal = {Frontiers in Pharmacology}, number = {1120}, issn = {1663-9812}, doi = {10.3389/fphar.2018.01120}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195985}, year = {2018}, abstract = {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.}, language = {en} } @article{SchaeferZhengvanBrederodeetal.2018, author = {Schaefer, Natascha and Zheng, Fang and van Brederode, Johannes and Berger, Alexandra and Leacock, Sophie and Hirata, Hiromi and Paige, Christopher J. and Harvey, Robert J. and Alzheimer, Christian and Villmann, Carmen}, title = {Functional Consequences of the Postnatal Switch From Neonatal to Mutant Adult Glycine Receptor α1 Subunits in the Shaky Mouse Model of Startle Disease}, series = {Frontiers in Molecular Neuroscience}, volume = {11}, journal = {Frontiers in Molecular Neuroscience}, number = {167}, issn = {1662-5099}, doi = {10.3389/fnmol.2018.00167}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196056}, year = {2018}, abstract = {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.}, language = {en} } @article{BahmerGupta2018, author = {Bahmer, Andreas and Gupta, Daya Shankar}, title = {Role of Oscillations in Auditory Temporal Processing: A General Model for Temporal Processing of Sensory Information in the Brain?}, series = {Frontiers in Neuroscience}, volume = {12}, journal = {Frontiers in Neuroscience}, number = {793}, issn = {1662-453X}, doi = {10.3389/fnins.2018.00793}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196087}, year = {2018}, abstract = {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.}, language = {en} } @article{GromerMadeiraGastetal.2018, author = {Gromer, Daniel and Madeira, Oct{\´a}via and Gast, Philipp and Nehfischer, Markus and Jost, Michael and M{\"u}ller, Mathias and M{\"u}hlberger, Andreas and Pauli, Paul}, title = {Height Simulation in a Virtual Reality CAVE System: Validity of Fear Responses and Effects of an Immersion Manipulation}, series = {Frontiers in Human Neuroscience}, volume = {12}, journal = {Frontiers in Human Neuroscience}, number = {372}, issn = {1662-5161}, doi = {10.3389/fnhum.2018.00372}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196113}, year = {2018}, abstract = {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.}, language = {en} } @article{VenturaBortWirknerGenheimeretal.2018, author = {Ventura-Bort, Carlos and Wirkner, Janine and Genheimer, Hannah and Wendt, Julia and Hamm, Alfons O. and Weymar, Mathias}, title = {Effects of Transcutaneous Vagus Nerve Stimulation (tVNS) on the P300 and Alpha-Amylase Level: A Pilot Study}, series = {Frontiers in Human Neuroscience}, volume = {12}, journal = {Frontiers in Human Neuroscience}, number = {202}, issn = {1662-5161}, doi = {10.3389/fnhum.2018.00202}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196129}, year = {2018}, abstract = {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.}, language = {en} } @article{MahyeraSchneiderHalligerKelleretal.2018, author = {Mahyera, Alexis S. and Schneider, Tamara and Halliger-Keller, Birgit and Schrooten, Katja and H{\"o}rner, Eva-Maria and Rost, Simone and Kress, Wolfram}, title = {Distribution and Structure of DM2 Repeat Tract Alleles in the German Population}, series = {Frontiers in Neurology}, volume = {9}, journal = {Frontiers in Neurology}, number = {463}, issn = {1664-2295}, doi = {10.3389/fneur.2018.00463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196252}, year = {2018}, abstract = {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.}, language = {en} } @article{PrustyChowdhuryGulveetal.2018, author = {Prusty, Bhupesh K. and Chowdhury, Suvagata R. and Gulve, Nitish and Rudel, Thomas}, title = {Peptidase Inhibitor 15 (PI15) Regulates Chlamydial CPAF Activity}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {8}, journal = {Frontiers in Cellular and Infection Microbiology}, number = {183}, issn = {2235-2988}, doi = {10.3389/fcimb.2018.00183}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196918}, year = {2018}, abstract = {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.}, language = {en} } @article{AnelliOrdasKneitzetal.2018, author = {Anelli, Viviana and Ordas, Anita and Kneitz, Susanne and Sagredo, Leonel Munoz and Gourain, Victor and Schartl, Manfred and Meijer, Annemarie H. and Mione, Marina}, title = {Ras-Induced miR-146a and 193a Target Jmjd6 to Regulate Melanoma Progression}, series = {Frontiers in Genetics}, volume = {9}, journal = {Frontiers in Genetics}, number = {675}, issn = {1664-8021}, doi = {10.3389/fgene.2018.00675}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196963}, year = {2018}, abstract = {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.}, language = {en} } @article{DasariShopovaStroeetal.2018, author = {Dasari, Prasad and Shopova, Iordana A. and Stroe, Maria and Wartenberg, Dirk and Martin-Dahse, Hans and Beyersdorf, Niklas and Hortschansky, Peter and Dietrich, Stefanie and Cseresny{\´e}s, Zolt{\´a}n and Figge, Marc Thilo and Westermann, Martin and Skerka, Christine and Brakhage, Axel A. and Zipfel, Peter F.}, title = {Aspf2 From Aspergillus fumigatus Recruits Human Immune Regulators for Immune Evasion and Cell Damage}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {1635}, issn = {1664-3224}, doi = {10.3389/fimmu.2018.01635}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197013}, year = {2018}, abstract = {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.}, language = {en} } @article{RhodesChenWilliamsonetal.2018, author = {Rhodes, David A. and Chen, Hung-Chang and Williamson, James C. and Hill, Alfred and Yuan, Jack and Smith, Sam and Rhodes, Harriet and Trowsdale, John and Lehner, Paul J. and Herrmann, Thomas and Eberl, Matthias}, title = {Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {662}, issn = {1664-3224}, doi = {10.3389/fimmu.2018.00662}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197054}, year = {2018}, abstract = {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.}, language = {en} } @article{PiegerMengelkampBannert2018, author = {Pieger, Elisabeth and Mengelkamp, Christoph and Bannert, Maria}, title = {Disfluency as a Desirable Difficulty — The Effects of Letter Deletion on Monitoring and Performance}, series = {Frontiers in Education}, volume = {3}, journal = {Frontiers in Education}, number = {101}, issn = {2504-284X}, doi = {10.3389/feduc.2018.00101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197179}, year = {2018}, abstract = {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.}, language = {en} } @article{BarYosefGildorRamirezZavalaetal.2018, author = {Bar-Yosef, Hagit and Gildor, Tsvia and Ram{\´i}rez-Zavala, Bernardo and Schmauch, Christian and Weissman, Ziva and Pinsky, Mariel and Naddaf, Rawi and Morschh{\"a}user, Joachim and Arkowitz, Robert A. and Kornitzer, Daniel}, title = {A global analysis of kinase function in Candida albicans hyphal morphogenesis reveals a role for the endocytosis regulator Akl1}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {8}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2018.00017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197204}, year = {2018}, abstract = {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.}, language = {en} } @article{NadellaMohantySharmaetal.2018, author = {Nadella, Vinod and Mohanty, Aparna and Sharma, Lalita and Yellaboina, Sailu and Mollenkopf, Hans-Joachim and Mazumdar, Varadendra Balaji and Palaparthi, Ramesh and Mylavarapu, Madhavi B. and Maurya, Radheshyam and Kurukuti, Sreenivasulu and Rudel, Thomas and Prakash, Hridayesh}, title = {Inhibitors of Apoptosis Protein Antagonists (Smac Mimetic Compounds) Control Polarization of Macrophages during Microbial Challenge and Sterile Inflammatory Responses}, series = {Frontiers in Immunology}, volume = {8}, journal = {Frontiers in Immunology}, number = {1792}, issn = {1664-3224}, doi = {10.3389/fimmu.2017.01792}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197484}, year = {2018}, abstract = {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.}, language = {en} } @article{PrausseLehnertTimmeetal.2018, author = {Prauße, Maria T. E. and Lehnert, Teresa and Timme, Sandra and H{\"u}nniger, Kerstin and Leonhardt, Ines and Kurzai, Oliver and Figge, Marc Thilo}, title = {Predictive Virtual Infection Modeling of Fungal Immune Evasion in Human Whole Blood}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {560}, issn = {1664-3224}, doi = {10.3389/fimmu.2018.00560}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197493}, year = {2018}, abstract = {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.}, language = {en} } @article{MuhammadRudolfPhametal.2018, author = {Muhammad, Khalid and Rudolf, Ronald and Pham, Duong Anh Thuy and Klein-Hessling, Stefan and Takata, Katsuyoshi and Matsushita, Nobuko and Ellenrieder, Volker and Kondo, Eisaku and  Serfling, Edgar}, title = {Induction of Short NFATc1/αA Isoform Interferes with Peripheral B Cell Differentiation}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {32}, issn = {1664-3224}, doi = {10.3389/fimmu.2018.00032}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197501}, year = {2018}, abstract = {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.}, language = {en} } @article{VolpatoHolzgrabe2018, author = {Volpato, Daniela and Holzgrabe, Ulrike}, title = {Designing Hybrids Targeting the Cholinergic System by Modulating the Muscarinic and Nicotinic Receptors: A Concept to Treat Alzheimer's Disease}, series = {Molecules}, volume = {23}, journal = {Molecules}, number = {12}, issn = {1420-3049}, doi = {10.3390/molecules23123230}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197555}, pages = {3230}, year = {2018}, abstract = {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.}, language = {en} } @article{ZielewskaBuettnerHeurichMuelleretal.2018, author = {Zielewska-B{\"u}ttner, Katarzyna and Heurich, Marco and M{\"u}ller, J{\"o}rg and Braunisch, Veronika}, title = {Remotely Sensed Single Tree Data Enable the Determination of Habitat Thresholds for the Three-Toed Woodpecker (Picoides tridactylus)}, series = {Remote Sensing}, volume = {10}, journal = {Remote Sensing}, number = {12}, issn = {2072-4292}, doi = {10.3390/rs10121972}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197565}, year = {2018}, abstract = {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.}, language = {en} } @article{ZimmererFischbachLatoschik2018, author = {Zimmerer, Chris and Fischbach, Martin and Latoschik, Marc Erich}, title = {Semantic Fusion for Natural Multimodal Interfaces using Concurrent Augmented Transition Networks}, series = {Multimodal Technologies and Interaction}, volume = {2}, journal = {Multimodal Technologies and Interaction}, number = {4}, issn = {2414-4088}, doi = {10.3390/mti2040081}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197573}, year = {2018}, abstract = {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.}, language = {en} } @article{RomoliChakrabortyDorneretal.2018, author = {Romoli, Carlo and Chakraborty, Nachiketa and Dorner, Daniela and Taylor, Andrew and Blank, Michael}, title = {Flux Distribution of Gamma-Ray Emission in Blazars: The Example of Mrk 501}, series = {Galaxies}, volume = {6}, journal = {Galaxies}, number = {4}, organization = {FACT and H.E.S.S. Collaborations}, issn = {2075-4434}, doi = {10.3390/galaxies6040135}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197580}, year = {2018}, abstract = {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}, language = {en} } @incollection{Schmitz2018, author = {Schmitz, Barbara}, title = {King and God : conceptions of rule and God in 3 Maccabees}, series = {Figures who shape scriptures, scriptures that shape figures}, booktitle = {Figures who shape scriptures, scriptures that shape figures}, doi = {10.1515/9783110596373-014}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205149}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {211-230}, year = {2018}, abstract = {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.}, language = {en} } @article{GrandeSoberatsHerbstetal.2018, author = {Grande, Vincenzo and Soberats, Bartolome and Herbst, Stefanie and Stepanenko, Vladimir and W{\"u}rthner, Frank}, title = {Hydrogen-bonded perylene bisimide J-aggregate aqua material}, volume = {9}, issn = {2041-6539}, doi = {10.1039/C8SC02409J}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204715}, pages = {6904-6911}, year = {2018}, abstract = {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.}, language = {en} } @article{HaggMayrMannigetal.2018, author = {Hagg, Wilfried and Mayr, Elisabeth and Mannig, Birgit and Reyers, Mark and Schubert, David and Pinto, Joaquim G. and Peters, Juliane and Pieczonka, Tino and Juen, Martin and Bolch, Tobias and Paeth, Heiko and Mayer, Christoph}, title = {Future climate change and its impact on runoff generation from the debris-covered Inylchek glaciers, Central Tian Shan, Kyrgyzstan}, series = {Water}, volume = {10}, journal = {Water}, number = {11}, issn = {2073-4441}, doi = {10.3390/w10111513}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197592}, pages = {1513}, year = {2018}, abstract = {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.}, language = {en} } @article{WeisShanKuhlmannetal.2018, author = {Weis, Matthias and Shan, Junwen and Kuhlmann, Matthias and Jungst, Tomasz and Tessmar, J{\"o}rg and Groll, J{\"u}rgen}, title = {Evaluation of hydrogels based on oxidized hyaluronic acid for bioprinting}, series = {Gels}, volume = {4}, journal = {Gels}, number = {4}, issn = {2310-2861}, doi = {10.3390/gels4040082}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197600}, pages = {82}, year = {2018}, abstract = {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.}, language = {en} } @article{KhanPirzadehFoersteretal.2018, author = {Khan, Muhammad Usman and Pirzadeh, Maryam and F{\"o}rster, Carola Yvette and Shityakov, Sergey and Shariati, Mohammad Ali}, title = {Role of milk-derived antibacterial peptides in modern food biotechnology: their synthesis, applications and future perspectives}, series = {Biomolecules}, volume = {8}, journal = {Biomolecules}, number = {4}, issn = {2218-273X}, doi = {10.3390/biom8040110}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197610}, pages = {110}, year = {2018}, abstract = {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.}, language = {en} } @article{MarzoccoFazeliDiMiccoetal.2018, author = {Marzocco, Stefania and Fazeli, Gholamreza and Di Micco, Lucia and Autore, Giuseppina and Adesso, Simona and Dal Piaz, Fabrizio and Heidland, August and Di Iorio, Biagio}, title = {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)}, series = {Journal of Clinical Medicine}, volume = {7}, journal = {Journal of Clinical Medicine}, number = {10}, issn = {2077-0383}, doi = {10.3390/jcm7100315}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197626}, pages = {315}, year = {2018}, abstract = {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.}, language = {en} } @article{YankuBitmanLotanZoharetal.2018, author = {Yanku, Yifat and Bitman-Lotan, Eliya and Zohar, Yaniv and Kurant, Estee and Zilke, Norman and Eilers, Martin and Orian, Amir}, title = {Drosophila HUWE1 ubiquitin ligase regulates endoreplication and antagonizes JNK signaling during salivary gland development}, series = {Cells}, volume = {7}, journal = {Cells}, number = {10}, issn = {2073-4409}, doi = {10.3390/cells7100151}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197630}, pages = {151}, year = {2018}, abstract = {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.}, language = {en} } @article{BuraBeaupreLegareetal.2018, author = {Bura, Thomas and Beaupr{\´e}, Serge and L{\´e}gar{\´e}, Marc-Andr{\´e} and Ibraikulov, Olzhas A. and Leclerc, Nicolas and Leclerc, Mario}, title = {Theoretical calculations for highly selective Direct Heteroarylation Polymerization: new nitrile-substituted Dithienyl-Diketopyrrolopyrrole-based polymers}, series = {Molecules}, volume = {23}, journal = {Molecules}, number = {9}, issn = {1420-3049}, doi = {10.3390/molecules23092324}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197648}, pages = {2324}, year = {2018}, abstract = {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.}, language = {en} } @article{NyamekyeThielSchoenbrodtStittetal.2018, author = {Nyamekye, Clement and Thiel, Michael and Sch{\"o}nbrodt-Stitt, Sarah and Zoungrana, Benewinde J.-B. and Amekudzi, Leonard K.}, title = {Soil and water conservation in Burkina Faso, West Africa}, series = {Sustainability}, volume = {10}, journal = {Sustainability}, number = {9}, issn = {2071-1050}, doi = {10.3390/su10093182}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197653}, pages = {3182}, year = {2018}, abstract = {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.}, language = {en} } @article{BencurovaGuptaSarukhanyanetal.2018, author = {Bencurova, Elena and Gupta, Shishir K. and Sarukhanyan, Edita and Dandekar, Thomas}, title = {Identification of antifungal targets based on computer modeling}, series = {Journal of Fungi}, volume = {4}, journal = {Journal of Fungi}, number = {3}, issn = {2309-608X}, doi = {10.3390/jof4030081}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197670}, pages = {81}, year = {2018}, abstract = {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.}, language = {en} } @article{LauschBorgBumbergeretal.2018, author = {Lausch, Angela and Borg, Erik and Bumberger, Jan and Dietrich, Peter and Heurich, Marco and Huth, Andreas and Jung, Andr{\´a}s and Klenke, Reinhard and Knapp, Sonja and Mollenhauer, Hannes and Paasche, Hendrik and Paulheim, Heiko and Pause, Marion and Schweitzer, Christian and Schmulius, Christiane and Settele, Josef and Skidmore, Andrew K. and Wegmann, Martin and Zacharias, Steffen and Kirsten, Toralf and Schaepman, Michael E.}, title = {Understanding forest health with remote sensing, part III: requirements for a scalable multi-source forest health monitoring network based on data science approaches}, series = {Remote Sensing}, volume = {10}, journal = {Remote Sensing}, number = {7}, issn = {2072-4292}, doi = {10.3390/rs10071120}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197691}, pages = {1120}, year = {2018}, abstract = {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.}, language = {en} } @article{DittmannBallesZabler2018, author = {Dittmann, Jonas and Balles, Andreas and Zabler, Simon}, title = {Optimization based evaluation of grating interferometric phase stepping series and analysis of mechanical setup instabilities}, series = {Journal of Imaging}, volume = {4}, journal = {Journal of Imaging}, number = {6}, issn = {2313-433X}, doi = {10.3390/jimaging4060077}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197723}, pages = {77}, year = {2018}, abstract = {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.}, language = {en} } @article{BoehmMeiningerTeschetal.2018, author = {Boehm, Anne and Meininger, Susanne and Tesch, Annemarie and Gbureck, Uwe and M{\"u}ller, Frank A.}, title = {The mechanical properties of biocompatible apatite bone cement reinforced with chemically activated carbon fibers}, series = {Materials}, volume = {11}, journal = {Materials}, number = {2}, issn = {1996-1944}, doi = {10.3390/ma11020192}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197808}, pages = {192}, year = {2018}, abstract = {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.}, language = {en} } @article{WeiBlaschke2018, author = {Wei, Chunzhu and Blaschke, Thomas}, title = {Pixel-wise vs. object-based impervious surface analysis from remote sensing: correlations with land surface temperature and population density}, series = {Urban Science}, volume = {2}, journal = {Urban Science}, number = {1}, issn = {2413-8851}, doi = {10.3390/urbansci2010002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197829}, pages = {2}, year = {2018}, abstract = {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.}, language = {en} } @unpublished{TitovHumeniukMitric2018, author = {Titov, Evgenii and Humeniuk, Alexander and Mitric, Roland}, title = {Exciton localization in excited-state dynamics of a tetracene trimer: A surface hopping LC-TDDFTB study}, series = {Physical Chemistry Chemical Physics}, journal = {Physical Chemistry Chemical Physics}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198680}, year = {2018}, abstract = {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.}, language = {en} } @article{MadanBayerGameretal.2018, author = {Madan, Christopher R. and Bayer, Janine and Gamer, Matthias and Lonsdorf, Tina B. and Sommer, Tobias}, title = {Visual Complexity and Affect: Ratings Reflect More Than Meets the Eye}, series = {Frontiers in Psychology}, volume = {8}, journal = {Frontiers in Psychology}, number = {2368}, issn = {1664-1078}, doi = {10.3389/fpsyg.2017.02368}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190015}, year = {2018}, abstract = {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.}, language = {en} } @article{TrafimowAmrheinAreshenkoffetal.2018, author = {Trafimow, David and Amrhein, Valentin and Areshenkoff, Corson N. and Barrera-Causil, Carlos J. and Beh, Eric J. and Bilgi{\c{c}}, Yusuf K. and Bono, Roser and Bradley, Michael T. and Briggs, William M. and Cepeda-Freyre, H{\´e}ctor A. and Chaigneau, Sergio E. and Ciocca, Daniel R. and Correa, Juan C. and Cousineau, Denis and de Boer, Michiel R. and Dhar, Subhra S. and Dolgov, Igor and G{\´o}mez-Benito, Juana and Grendar, Marian and Grice, James W. and Guerrero-Gimenez, Martin E. and Guti{\´e}rrez, Andr{\´e}s and Huedo-Medina, Tania B. and Jaffe, Klaus and Janyan, Armina and Karimnezhad, Ali and Korner-Nievergelt, Fr{\"a}nzi and Kosugi, Koji and Lachmair, Martin and Ledesma, Rub{\´e}n D. and Limongi, Roberto and Liuzza, Marco T. and Lombardo, Rosaria and Marks, Michael J. and Meinlschmidt, Gunther and Nalborczyk, Ladislas and Nguyen, Hung T. and Ospina, Raydonal and Perezgonzalez, Jose D. and Pfister, Roland and Rahona, Juan J. and Rodr{\´i}guez-Medina, David A. and Rom{\~a}o, Xavier and Ruiz-Fern{\´a}ndez, Susana and Suarez, Isabel and Tegethoff, Marion and Tejo, Mauricio and van de Schoot, Rens and Vankov, Ivan I. and Velasco-Forero, Santiago and Wang, Tonghui and Yamada, Yuki and Zoppino, Felipe C. M. and Marmolejo-Ramos, Fernando}, title = {Manipulating the Alpha Level Cannot Cure Significance Testing}, series = {Frontiers in Psychology}, volume = {9}, journal = {Frontiers in Psychology}, number = {699}, issn = {1664-1078}, doi = {10.3389/fpsyg.2018.00699}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189973}, year = {2018}, abstract = {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.}, language = {en} } @article{SchwabHennighausenAdleretal.2018, author = {Schwab, Frank and Hennighausen, Christine and Adler, Dorothea C. and Carolus, Astrid}, title = {Television Is Still "Easy" and Print Is Still "Tough"? More Than 30 Years of Research on the Amount of Invested Mental Effort}, series = {Frontiers in Psychology}, volume = {9}, journal = {Frontiers in Psychology}, number = {1098}, issn = {1664-1078}, doi = {10.3389/fpsyg.2018.01098}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189965}, year = {2018}, abstract = {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.}, language = {en} } @article{WolffWeikampBatinic2018, author = {Wolff, Hans-Georg and Weikamp, Julia G. and Batinic, Bernad}, title = {Implicit Motives as Determinants of Networking Behaviors}, series = {Frontiers in Psychology}, volume = {9}, journal = {Frontiers in Psychology}, number = {411}, issn = {1664-1078}, doi = {10.3389/fpsyg.2018.00411}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189954}, year = {2018}, abstract = {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.}, language = {en} } @article{NaglerNaegeleGillietal.2018, author = {Nagler, Matthias and N{\"a}gele, Thomas and Gilli, Christian and Fragner, Lena and Korte, Arthur and Platzer, Alexander and Farlow, Ashley and Nordborg, Magnus and Weckwerth, Wolfram}, title = {Eco-Metabolomics and Metabolic Modeling: Making the Leap From Model Systems in the Lab to Native Populations in the Field}, series = {Frontiers in Plant Science}, volume = {9}, journal = {Frontiers in Plant Science}, number = {1556}, issn = {1664-462X}, doi = {10.3389/fpls.2018.01556}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189560}, year = {2018}, abstract = {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.}, language = {en} } @unpublished{WernerBundschuhBundschuhetal.2018, author = {Werner, Rudolf A. and Bundschuh, Ralph A. and Bundschuh, Lena and Javadi, Mehrbod S. and Leal, Jeffrey P. and Higuchi, Takahiro and Pienta, Kenneth J. and Buck, Andreas K. and Pomper, Martin G. and Gorin, Michael A. and Lapa, Constantin and Rowe, Steven P.}, title = {Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging}, series = {Journal of Nuclear Medicine}, journal = {Journal of Nuclear Medicine}, issn = {0161-5505}, doi = {10.2967/jnumed.118.217588}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167788}, year = {2018}, abstract = {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.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @article{ChtourouEngelFakhfakhetal.2018, author = {Chtourou, Hamdi and Engel, Florian Azad and Fakhfakh, Hassen and Fakhfakh, Hazem and Hammouda, Omar and Ammar, Achraf and Trabelsi, Khaled and Souissi, Nizar and Sperlich, Billy}, title = {Diurnal Variation of Short-Term Repetitive Maximal Performance and Psychological Variables in Elite Judo Athletes}, series = {Frontiers in Physiology}, volume = {9}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2018.01499}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189269}, pages = {1409}, year = {2018}, abstract = {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.}, language = {en} } @article{AkhrifRomanosDomschkeetal.2018, author = {Akhrif, Atae and Romanos, Marcel and Domschke, Katharina and Schmitt-Boehrer, Angelika and Neufang, Susanne}, title = {Fractal Analysis of BOLD Time Series in a Network Associated With Waiting Impulsivity}, series = {Frontiers in Physiology}, volume = {9}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2018.01378}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189191}, pages = {1378}, year = {2018}, abstract = {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.}, language = {en} } @article{EngelAckermannChtourouetal.2018, author = {Engel, Florian Azad and Ackermann, Alexander and Chtourou, Hamdi and Sperlich, Billy}, title = {High-Intensity Interval Training Performed by Young Athletes: A Systematic Review and Meta-Analysis}, series = {Frontiers in Physiology}, volume = {9}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2018.01012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189173}, pages = {1012}, year = {2018}, abstract = {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.}, language = {en} } @article{FussDuekingWeizman2018, author = {Fuss, Franz Konstantin and D{\"u}king, Peter and Weizman, Yehuda}, title = {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}, series = {Frontiers in Physiology}, volume = {9}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2018.00063}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189126}, pages = {63}, year = {2018}, abstract = {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.}, language = {en} } @phdthesis{GilPulido2018, author = {Gil Pulido, Jes{\´u}s}, title = {The role of Batf3-dependent dendritic cells and the IL-23 receptor in atherosclerosis}, doi = {10.25972/OPUS-16720}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167203}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {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.}, subject = {Arteriosklerose}, language = {en} } @unpublished{YinWernerHiguchietal.2018, author = {Yin, Yafu and Werner, Rudolf A. and Higuchi, Takahiro and Lapa, Constantin and Pienta, Kenneth J. and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P.}, title = {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}, series = {Journal of Nuclear Medicine}, journal = {Journal of Nuclear Medicine}, issn = {0161-5505}, doi = {10.2967/jnumed.118.217653}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167594}, year = {2018}, abstract = {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.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @article{SchairerWagnerGeidel2018, author = {Schairer, Patrick and Wagner, Stephan and Geidel, Ekkehard}, title = {An experimental introduction to basic principles of the interaction of electromagnetic radiation with matter}, series = {World Journal of Chemical Education}, volume = {6}, journal = {World Journal of Chemical Education}, number = {1}, doi = {10.12691/wjce-6-1-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175811}, pages = {29-35}, year = {2018}, abstract = {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.}, language = {en} } @article{GrossheinrichFirkSchulteRuetheretal.2018, author = {Grossheinrich, Nicola and Firk, Christine and Schulte-R{\"u}ther, Martin and von Leupoldt, Andreas and Konrad, Kerstin and Huestegge, Lynn}, title = {Looking while unhappy: a mood-congruent attention bias toward sad adult faces in children}, series = {Frontiers in Psychology}, volume = {9}, journal = {Frontiers in Psychology}, number = {2577}, doi = {10.3389/fpsyg.2018.02577}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177688}, year = {2018}, abstract = {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.}, language = {en} } @article{RauSchmittBergetal.2018, author = {Rau, Monika and Schmitt, Johannes and Berg, Thomas and Kremer, Andreas E. and Stieger, Bruno and Spanaus, Katharina and Bengsch, Bertram and Romero, Marta R. and Marin, Jose J. and Keitel, Verena and Klinker, Hartwig and Tony, Hans-Peter and M{\"u}llhaupt, Beat and Geier, Andreas}, title = {Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0208225}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177674}, pages = {e0208225}, year = {2018}, abstract = {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.}, language = {en} }