@article{AndreattaPauli2019, author = {Andreatta, Marta and Pauli, Paul}, title = {Generalization of appetitive conditioned responses}, series = {Psychophysiology}, volume = {56}, journal = {Psychophysiology}, doi = {10.1111/psyp.13397}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221132}, year = {2019}, abstract = {A stimulus (conditioned stimulus, CS) associated with an appetitive unconditioned stimulus (US) acquires positive properties and elicits appetitive conditioned responses (CR). Such associative learning has been examined extensively in animals with food as the US, and results are used to explain psychopathologies (e.g., substance-related disorders or obesity). Human studies on appetitive conditioning exist, too, but we still know little about generalization processes. Understanding these processes may explain why stimuli not associated with a drug, for instance, can elicit craving. Forty-seven hungry participants underwent an appetitive conditioning protocol during which one of two circles with different diameters (CS+) became associated with an appetitive US (chocolate or salty pretzel, according to participants' preference) but never the other circle (CS-). During generalization, US were delivered twice and the two CS were presented again plus four circles (generalization stimuli, GS) with gradually increasing diameters from CS- to CS+. We found successful appetitive conditioning as reflected in appetitive subjective ratings (positive valence, higher contingency) and physiological responses (startle attenuation and larger skin conductance responses) to CS+ versus CS-, and, importantly, both measures confirmed generalization as indicated by generalization gradients. Small changes in CS-US contingency during generalization may have weakened generalization processes on the physiological level. Considering that appetitive conditioned responses can be generalized to non-US-associated stimuli, a next important step would be to investigate risk factors that mediate overgeneralization.}, language = {en} } @article{Chevalier‐RoignantFlathTrigeorgis2019, author = {Chevalier-Roignant, Beno{\^i}t and Flath, Christoph M. and Trigeorgis, Lenos}, title = {Disruptive Innovation, Market Entry and Production Flexibility in Heterogeneous Oligopoly}, series = {Production and Operations Management}, volume = {28}, journal = {Production and Operations Management}, doi = {10.1111/poms.12995}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-356226}, pages = {1641-1657}, year = {2019}, abstract = {We develop a model of oligopoly competition involving innovation effort, market entry and production flexibility under demand uncertainty. Several heterogeneous firms make efforts to develop new prototypes; if they succeed, they hold a shared option to enter a new market under stochastic demand. We derive analytic results for the Markov perfect equilibrium accounting for development effort, market entry and production decisions and complement these by numerical analyses. Firm value—which embeds real options—is not convex increasing in demand but exhibits "competitive waves" due to market entries by rivals. A firm with a development advantage ("innovator") exerts greater innovation effort if the market is a niche, whereas another benefiting from economies of scale ("incumbent") invests more if the market is larger. Positive externalities benefit the incumbent in the development stage, whereas the innovator is better off in counteracting negative externalities. Demand volatility raises firm incentives to innovate as it enhances the value of firm market-entry and production flexibility.}, language = {en} } @article{HuangWaadtNuhkatetal.2019, author = {Huang, Shouguang and Waadt, Rainer and Nuhkat, Maris and Kollist, Hannes and Hedrich, Rainer and Roelfsema, M. Rob G.}, title = {Calcium signals in guard cells enhance the efficiency by which abscisic acid triggers stomatal closure}, series = {New Phytologist}, volume = {224}, journal = {New Phytologist}, doi = {10.1111/nph.15985}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322716}, pages = {177-187}, year = {2019}, abstract = {During drought, abscisic acid (ABA) induces closure of stomata via a signaling pathway that involves the calcium (Ca2+)-independent protein kinase OST1, as well as Ca2+-dependent protein kinases. However, the interconnection between OST1 and Ca2+ signaling in ABA-induced stomatal closure has not been fully resolved. ABA-induced Ca2+ signals were monitored in intact Arabidopsis leaves, which express the ratiometric Ca2+ reporter R-GECO1-mTurquoise and the Ca2+-dependent activation of S-type anion channels was recorded with intracellular double-barreled microelectrodes. ABA triggered Ca2+ signals that occurred during the initiation period, as well as in the acceleration phase of stomatal closure. However, a subset of stomata closed in the absence of Ca2+ signals. On average, stomata closed faster if Ca2+ signals were elicited during the ABA response. Loss of OST1 prevented ABA-induced stomatal closure and repressed Ca2+ signals, whereas elevation of the cytosolic Ca2+ concentration caused a rapid activation of SLAC1 and SLAH3 anion channels. Our data show that the majority of Ca2+ signals are evoked during the acceleration phase of stomatal closure, which is initiated by OST1. These Ca2+ signals are likely to activate Ca2+-dependent protein kinases, which enhance the activity of S-type anion channels and boost stomatal closure.}, language = {en} } @article{WanZhangPruittetal.2019, author = {Wan, Wei-Lin and Zhang, Lisha and Pruitt, Rory and Zaidem, Maricris and Brugman, Rik and Ma, Xiyu and Krol, Elzbieta and Perraki, Artemis and Kilian, Joachim and Grossmann, Guido and Stahl, Mark and Shan, Libo and Zipfel, Cyril and van Kan, Jan A. L. and Hedrich, Rainer and Weigel, Detlef and Gust, Andrea A. and N{\"u}rnberger, Thorsten}, title = {Comparing Arabidopsis receptor kinase and receptor protein-mediated immune signaling reveals BIK1-dependent differences}, series = {New Phytologist}, volume = {221}, journal = {New Phytologist}, doi = {10.1111/nph.15497}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233385}, pages = {2080-2095}, year = {2019}, abstract = {Pattern recognition receptors (PRRs) sense microbial patterns and activate innate immunity against attempted microbial invasions. The leucine-rich repeat receptor kinases (LRR-RK) FLS2 and EFR, and the LRR receptor protein (LRR-RP) receptors RLP23 and RLP42, respectively, represent prototypical members of these two prominent and closely related PRR families. We conducted a survey of Arabidopsis thaliana immune signaling mediated by these receptors to address the question of commonalities and differences between LRR-RK and LRR-RP signaling. Quantitative differences in timing and amplitude were observed for several early immune responses, with RP-mediated responses typically being slower and more prolonged than those mediated by RKs. Activation of RLP23, but not FLS2, induced the production of camalexin. Transcriptomic analysis revealed that RLP23-regulated genes represent only a fraction of those genes differentially expressed upon FLS2 activation. Several positive and negative regulators of FLS2-signaling play similar roles in RLP23 signaling. Intriguingly, the cytoplasmic receptor kinase BIK1, a positive regulator of RK signaling, acts as a negative regulator of RP-type immune receptors in a manner dependent on BIK1 kinase activity. Our study unveiled unexpected differences in two closely related receptor systems and reports a new negative role of BIK1 in plant immunity.}, language = {en} } @article{MerkiesvanSchaikLegeretal.2019, author = {Merkies, Ingemar S.J. and van Schaik, Ivo N. and L{\´e}ger, Jean-Marc and Bril, Vera and van Geloven, Nan and Hartung, Hans-Peter and Lewis, Richard A. and Sobue, Gen and Lawo, John-Philip and Durn, Billie L. and Cornblath, David R. and De Bleecker, Jan L. and Sommer, Claudia and Robberecht, Wim and Saarela, Mika and Kamienowski, Jerzy and Stelmasiak, Zbigniew and Tackenberg, Bj{\"o}rn and Mielke, Orell}, title = {Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies}, series = {Journal of the Peripheral Nervous System}, volume = {24}, journal = {Journal of the Peripheral Nervous System}, organization = {PRIMA Trial Investigators and the PATH Study Group}, doi = {10.1111/jns.12302}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224013}, pages = {48-55}, year = {2019}, abstract = {Intravenous immunoglobulin (IVIG) is a potential therapy for chronic inflammatory demyelinating polyneuropathy (CIDP). To investigate the efficacy and safety of the IVIG IgPro10 (Privigen) for treatment of CIDP, results from Privigen Impact on Mobility and Autonomy (PRIMA), a prospective, open-label, single-arm study of IVIG in immunoglobulin (Ig)-na{\"i}ve or IVIG pre-treated subjects (NCT01184846, n = 28) and Polyneuropathy And Treatment with Hizentra (PATH), a double-blind, randomized study including an open-label, single-arm IVIG phase in IVIG pre-treated subjects (NCT01545076, IVIG restabilization phase n = 207) were analyzed separately and together (n = 235). Efficacy assessments included change in adjusted inflammatory neuropathy cause and treatment (INCAT) score, grip strength and Medical Research Council (MRC) sum score. Adverse drug reactions (ADRs) and ADRs/infusion were recorded. Adjusted INCAT response rate was 60.7\% in all PRIMA subjects at Week 25 (76.9\% in IVIG pre-treated subjects) and 72.9\% in PATH. In the pooled cohort (n = 235), INCAT response rate was 71.5\%; median time to INCAT improvement was 4.3 weeks. No clear demographic differences were noticed between early (responding before Week 7, n = 148) and late responders (n = 21). In the pooled cohort, median change from baseline to last observation was -1.0 (interquartile range -2.0; 0.0) point for INCAT score; +8.0 (0.0; 20.0) kPa for maximum grip strength; +3.0 (1.0; 7.0) points for MRC sum score. In the pooled cohort, 271 ADRs were reported in 105 subjects (44.7\%), a rate of 0.144 ADRs per infusion. This analysis confirms the efficacy and safety of IgPro10, a recently FDA-approved IVIG for CIDP, in a population of mainly pre-treated subjects with CIDP [Correction added on 14 March 2019 after first online publication: the INCAT response rate has been corrected.].}, language = {en} } @article{KadowakiNangakuHanteletal.2019, author = {Kadowaki, Takashi and Nangaku, Masaomi and Hantel, Stefan and Okamura, Tomoo and von Eynatten, Maximilian and Wanner, Christoph and Koitka-Weber, Audrey}, title = {Empagliflozin and kidney outcomes in Asian patients with type 2 diabetes and established cardiovascular disease: Results from the EMPA-REG OUTCOME® trial}, series = {Journal of Diabetes Investigation}, volume = {10}, journal = {Journal of Diabetes Investigation}, doi = {10.1111/jdi.12971}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325246}, pages = {760-770}, year = {2019}, abstract = {Aims/Introduction In the EMPA-REG OUTCOME® trial, empagliflozin added to standard of care improved clinically relevant kidney outcomes by 39\%, slowed progression of chronic kidney disease, and reduced albuminuria in patients with type 2 diabetes and established cardiovascular disease. This exploratory analysis investigated the effects of empagliflozin on the kidneys in Asian patients. Materials and Methods Participants in the EMPA-REG OUTCOME® trial were randomized (1:1:1) to empagliflozin 10 mg, 25 mg or a placebo. In patients of Asian race, we analyzed incident or worsening nephropathy (progression to macroalbuminuria, doubling of serum creatinine, initiation of renal-replacement therapy or renal death) and its components, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio changes, and renal safety. Results Of 7,020 treated patients, 1,517 (26.1\%) were Asian. In this subgroup, consistent with the overall trial population, empagliflozin reduced the risk of incident or worsening nephropathy (hazard ratio 0.64, 95\% confidence interval 0.49-0.83), progression to macroalbuminuria (hazard ratio 0.64, 95\% confidence interval 0.49-0.85) and the composite of doubling of serum creatinine, initiation of renal-replacement therapy or renal death (hazard ratio 0.48, 95\% confidence interval 0.25-0.92). Furthermore, empagliflozin-treated participants showed slower eGFR decline versus placebo, and showed rapid urine albumin-to-creatinine ratio reduction at week 12, maintained through week 164, with effects most pronounced in those with baseline microalbuminuria or macroalbuminuria. The kidney safety profile of empagliflozin in the Asian subgroup was similar to the overall trial population. Conclusions In Asian patients from the EMPA-REG OUTCOME® trial, empagliflozin improved kidney outcomes, slowed eGFR decline and lowered albuminuria versus placebo, consistent with the overall trial population findings.}, language = {en} } @article{EickholzKochKocheretal.2019, author = {Eickholz, Peter and Koch, Raphael and Kocher, Thomas and Hoffmann, Thomas and Kim, Ti-Sun and Meyle, Joerg and Kaner, Doğan and Schlagenhauf, Ulrich and Harmsen, Dag and Harks, Inga and Ehmke, Benjamin}, title = {Clinical benefits of systemic amoxicillin/metronidazole may depend on periodontitis severity and patients' age: An exploratory sub-analysis of the ABPARO trial}, series = {Journal of Clinical Periodontology}, volume = {46}, journal = {Journal of Clinical Periodontology}, doi = {10.1111/jcpe.13096}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226579}, pages = {491-501}, year = {2019}, abstract = {Aim The aim was to identify benefit thresholds for clinical variables. We hypothesize, if variables fall below or exceed these threshold levels, systemic amoxicillin/metronidazole may contribute to reducing progression of periodontitis. Material \& Methods This is an explorative per-protocol collective analysis (n = 345) conducted on the placebo-controlled, multi-centre ABPARO trial (ClinicalTrials.gov NCT00707369). Patients received debridement with systemic amoxicillin 500 mg/metronidazole 400 mg (3×/day, 7 days, n = 170) or placebo (n = 175) and maintenance therapy every three months. To identify thresholds, each of the following baseline characteristics was classified into two groups (≥threshold value/ 5 mm (5.2\%) at baseline compared to the placebo (9.0\%, 11.6\%, and 12.5\%, respectively; p < 0.005). Conclusions The clinical benefits of systemic amoxicillin/metronidazole may depend on periodontitis severity and patients' age.}, language = {en} } @article{LaemmermannKastenmueller2019, author = {L{\"a}mmermann, Tim and Kastenm{\"u}ller, Wolfgang}, title = {Concepts of GPCR-controlled navigation in the immune system}, series = {Immunological Reviews}, volume = {289}, journal = {Immunological Reviews}, doi = {10.1111/imr.12752}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236357}, pages = {205-231}, year = {2019}, abstract = {G-protein-coupled receptor (GPCR) signaling is essential for the spatiotemporal control of leukocyte dynamics during immune responses. For efficient navigation through mammalian tissues, most leukocyte types express more than one GPCR on their surface and sense a wide range of chemokines and chemoattractants, leading to basic forms of leukocyte movement (chemokinesis, haptokinesis, chemotaxis, haptotaxis, and chemorepulsion). How leukocytes integrate multiple GPCR signals and make directional decisions in lymphoid and inflamed tissues is still subject of intense research. Many of our concepts on GPCR-controlled leukocyte navigation in the presence of multiple GPCR signals derive from in vitro chemotaxis studies and lower vertebrates. In this review, we refer to these concepts and critically contemplate their relevance for the directional movement of several leukocyte subsets (neutrophils, T cells, and dendritic cells) in the complexity of mouse tissues. We discuss how leukocyte navigation can be regulated at the level of only a single GPCR (surface expression, competitive antagonism, oligomerization, homologous desensitization, and receptor internalization) or multiple GPCRs (synergy, hierarchical and non-hierarchical competition, sequential signaling, heterologous desensitization, and agonist scavenging). In particular, we will highlight recent advances in understanding GPCR-controlled leukocyte navigation by intravital microscopy of immune cells in mice.}, language = {en} } @article{ThomasMyers‐SmithBjorkmanetal.2019, author = {Thomas, H. J. D. and Myers-Smith, I. H. and Bjorkman, A. D. and Elmendorf, S. C. and Blok, D. and Cornelissen, J. H. C. and Forbes, B. C. and Hollister, R. D. and Normand, S. and Prev{\´e}y, J. S. and Rixen, C. and Schaepman-Strub, G. and Wilmking, M. and Wipf, S. and Cornwell, W. K. and Kattge, J. and Goetz, S. J. and Guay, K. C. and Alatalo, J. M. and Anadon-Rosell, A. and Angers-Blondin, S. and Berner, L. T. and Bj{\"o}rk, R. G. and Buchwal, A. and Buras, A. and Carbognani, M. and Christie, K. and Siegwart Collier, L. and Cooper, E. J. and Eskelinen, A. and Frei, E. R. and Grau, O. and Grogan, P. and Hallinger, M. and Heijmans, M. M. P. D. and Hermanutz, L. and Hudson, J. M. G. and H{\"u}lber, K. and Iturrate-Garcia, M. and Iversen, C. M. and Jaroszynska, F. and Johnstone, J. F. and Kaarlej{\"a}rvi, E. and Kulonen, A. and Lamarque, L. J. and L{\´e}vesque, E. and Little, C. J. and Michelsen, A. and Milbau, A. and Nabe-Nielsen, J. and Nielsen, S. S. and Ninot, J. M. and Oberbauer, S. F. and Olofsson, J. and Onipchenko, V. G. and Petraglia, A. and Rumpf, S. B. and Semenchuk, P. R. and Soudzilovskaia, N. A. and Spasojevic, M. J. and Speed, J. D. M. and Tape, K. D. and te Beest, M. and Tomaselli, M. and Trant, A. and Treier, U. A. and Venn, S. and Vowles, T. and Weijers, S. and Zamin, T. and Atkin, O. K. and Bahn, M. and Blonder, B. and Campetella, G. and Cerabolini, B. E. L. and Chapin III, F. S. and Dainese, M. and de Vries, F. T. and D{\´i}az, S. and Green, W. and Jackson, R. B. and Manning, P. and Niinemets, {\"U}. and Ozinga, W. A. and Pe{\~n}uelas, J. and Reich, P. B. and Schamp, B. and Sheremetev, S. and van Bodegom, P. M.}, title = {Traditional plant functional groups explain variation in economic but not size-related traits across the tundra biome}, series = {Global Ecology and Biogeography}, volume = {28}, journal = {Global Ecology and Biogeography}, doi = {10.1111/geb.12783}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241310}, pages = {78-95}, year = {2019}, abstract = {Aim Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits. Location Tundra biome. Time period Data collected between 1964 and 2016. Major taxa studied 295 tundra vascular plant species. Methods We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species-level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species-level traits. Results Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19\% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species-level trait expression. Main conclusions Traditional functional groups only coarsely represent variation in well-measured traits within tundra plant communities, and better explain resource economic traits than size-related traits. We recommend caution when using functional group approaches to predict tundra vegetation change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insights for ecological prediction and modelling.}, language = {en} } @article{OPUS4-31382, title = {Dijet azimuthal correlations and conditional yields in \({pp}\) and \(p\) + Pb collisions at √S-NN=5.02 TeV with the ATLAS detector}, series = {Physical Review C}, volume = {100}, journal = {Physical Review C}, number = {3}, organization = {The ATLAS Collaboration}, doi = {10.1103/PhysRevC.100.034903}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313823}, pages = {1-24}, year = {2019}, abstract = {This paper presents a measurement of forward-forward and forward-central dijet azimuthal angular correlations and conditional yields in proton-proton (pp) and proton-lead (p + Pb) collisions as a probe of the nuclear gluon density in regions where the fraction of the average momentum per nucleon carried by the parton entering the hard scattering is low. In these regions, gluon saturation can modify the rapidly increasing parton distribution function of the gluon. The analysis utilizes 25 pb(-1) of pp data and 360 mu b(-1) of p + Pb data, both at root S-NN = 5.02 TeV, collected in 2015 and 2016, respectively, with the ATLAS detector at the Large Hadron Collider. The measurement is performed in the center-of-mass frame of the nucleon-nucleon system in the rapidity range between -4.0 and 4.0 using the two highest transverse-momentum jets in each event, with the highest transverse-momentum jet restricted to the forward rapidity range. No significant broadening of azimuthal angular correlations is observed for forward-forward or forward-central dijets in p + Pb compared to pp collisions. For forward-forward jet pairs in the proton-going direction, the ratio of conditional yields in p + Pb collisions to those in pp collisions is suppressed by approximately 20\%, with no significant dependence on the transverse momentum of the dijet system. No modification of conditional yields is observed for forward-central dijets.}, language = {en} } @article{MuellerNossThornetal.2019, author = {M{\"u}ller, J{\"o}rg and Noss, Reed F. and Thorn, Simon and B{\"a}ssler, Claus and Leverkus, Alexandro B. and Lindenmayer, David}, title = {Increasing disturbance demands new policies to conserve intact forest}, series = {Conservation Letters}, volume = {12}, journal = {Conservation Letters}, doi = {10.1111/conl.12449}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224256}, year = {2019}, abstract = {Ongoing controversy over logging the ancient Białowieża Forest in Poland symbolizes a global problem for policies and management of the increasing proportion of the earth's intact forest that is subject to postdisturbance logging. We review the extent of, and motivations for, postdisturbance logging in protected and unprotected forests globally. An unprecedented level of logging in protected areas and other places where green-tree harvest would not normally occur is driven by economic interests and a desire for pest control. To avoid failure of global initiatives dedicated to reducing the loss of species, five key policy reforms are necessary: (1) salvage logging must be banned from protected areas; (2) forest planning should address altered disturbance regimes for all intact forests to ensure that significant areas remain undisturbed by logging; (3) new kinds of integrated analyses are needed to assess the potential economic benefits of salvage logging against its ecological, economic, and social costs; (4) global and regional maps of natural disturbance regimes should be created to guide better spatiotemporal planning of protected areas and undisturbed forests outside reserves; and (5) improved education and communication programs are needed to correct widely held misconceptions about natural disturbances.}, language = {en} } @article{IngendohTsakmakidisMikolaiWinkeletal.2019, author = {Ingendoh-Tsakmakidis, Alexandra and Mikolai, Carina and Winkel, Andreas and Szafrański, Szymon P. and Flak, Christine S. and Rossi, Angela and Walles, Heike and Stiesch, Meike}, title = {Commensal and pathogenic biofilms differently modulate peri-implant oral mucosa in an organotypic model}, series = {Cellular Microbiology}, volume = {21}, journal = {Cellular Microbiology}, doi = {10.1111/cmi.13078}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323077}, year = {2019}, abstract = {The impact of oral commensal and pathogenic bacteria on peri-implant mucosa is not well understood, despite the high prevalence of peri-implant infections. Hence, we investigated responses of the peri-implant mucosa to Streptococcus oralis or Aggregatibacter actinomycetemcomitans biofilms using a novel in vitro peri-implant mucosa-biofilm model. Our 3D model combined three components, organotypic oral mucosa, implant material, and oral biofilm, with structural assembly close to native situation. S. oralis induced a protective stress response in the peri-implant mucosa through upregulation of heat shock protein (HSP70) genes. Attenuated inflammatory response was indicated by reduced cytokine levels of interleukin-6 (IL-6), interleukin-8 (CXCL8), and monocyte chemoattractant protein-1 (CCL2). The inflammatory balance was preserved through increased levels of tumor necrosis factor-alpha (TNF-α). A. actinomycetemcomitans induced downregulation of genes important for cell survival and host inflammatory response. The reduced cytokine levels of chemokine ligand 1 (CXCL1), CXCL8, and CCL2 also indicated a diminished inflammatory response. The induced immune balance by S. oralis may support oral health, whereas the reduced inflammatory response to A. actinomycetemcomitans may provide colonisation advantage and facilitate later tissue invasion. The comprehensive characterisation of peri-implant mucosa-biofilm interactions using our 3D model can provide new knowledge to improve strategies for prevention and therapy of peri-implant disease.}, language = {en} } @article{ZeinerPreusseGolebiewskaetal.2019, author = {Zeiner, Pia S. and Preusse, Corinna and Golebiewska, Anna and Zinke, Jenny and Iriondo, Ane and Muller, Arnaud and Kaoma, Tony and Filipski, Katharina and M{\"u}ller-Eschner, Monika and Bernatz, Simon and Blank, Anna-Eva and Baumgarten, Peter and Ilina, Elena and Grote, Anne and Hansmann, Martin L. and Verhoff, Marcel A. and Franz, Kea and Feuerhake, Friedrich and Steinbach, Joachim P. and Wischhusen, J{\"o}rg and Stenzel, Werner and Niclou, Simone P. and Harter, Patrick N. and Mittelbronn, Michel}, title = {Distribution and prognostic impact of microglia/macrophage subpopulations in gliomas}, series = {Brain Pathology}, volume = {29}, journal = {Brain Pathology}, doi = {10.1111/bpa.12690}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233897}, pages = {513-529}, year = {2019}, abstract = {While the central nervous system is considered an immunoprivileged site and brain tumors display immunosuppressive features, both innate and adaptive immune responses affect glioblastoma (GBM) growth and treatment resistance. However, the impact of the major immune cell population in gliomas, represented by glioma-associated microglia/macrophages (GAMs), on patients' clinical course is still unclear. Thus, we aimed at assessing the immunohistochemical expression of selected microglia and macrophage markers in 344 gliomas (including gliomas from WHO grade I-IV). Furthermore, we analyzed a cohort of 241 IDH1R132H-non-mutant GBM patients for association of GAM subtypes and patient overall survival. Phenotypical properties of GAMs, isolated from high-grade astrocytomas by CD11b-based magnetic cell sorting, were analyzed by immunocytochemistry, mRNA microarray, qRT-PCR and bioinformatic analyses. A higher amount of CD68-, CD163- and CD206-positive GAMs in the vital tumor core was associated with beneficial patient survival. The mRNA expression profile of GAMs displayed an upregulation of factors that are considered as pro-inflammatory M1 (eg, CCL2, CCL3L3, CCL4, PTGS2) and anti-inflammatory M2 polarization markers (eg, MRC1, LGMN, CD163, IL10, MSR1), the latter rather being associated with phagocytic functions in the GBM microenvironment. In summary, we present evidence that human GBMs contain mixed M1/M2-like polarized GAMs and that the levels of different GAM subpopulations in the tumor core are positively associated with overall survival of patients with IDH1R132H-non-mutant GBMs.}, language = {en} } @article{BahramAnslanHildebrandetal.2019, author = {Bahram, Mohammad and Anslan, Sten and Hildebrand, Falk and Bork, Peer and Tedersoo, Leho}, title = {Newly designed 16S rRNA metabarcoding primers amplify diverse and novel archaeal taxa from the environment}, series = {Environmental Microbiology Reports}, volume = {11}, journal = {Environmental Microbiology Reports}, doi = {10.1111/1758-2229.12684}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221380}, pages = {487-494}, year = {2019}, abstract = {High-throughput studies of microbial communities suggest that Archaea are a widespread component of microbial diversity in various ecosystems. However, proper quantification of archaeal diversity and community ecology remains limited, as sequence coverage of Archaea is usually low owing to the inability of available prokaryotic primers to efficiently amplify archaeal compared to bacterial rRNA genes. To improve identification and quantification of Archaea, we designed and validated the utility of several primer pairs to efficiently amplify archaeal 16S rRNA genes based on up-to-date reference genes. We demonstrate that several of these primer pairs amplify phylogenetically diverse Archaea with high sequencing coverage, outperforming commonly used primers. Based on comparing the resulting long 16S rRNA gene fragments with public databases from all habitats, we found several novel family- to phylum-level archaeal taxa from topsoil and surface water. Our results suggest that archaeal diversity has been largely overlooked due to the limitations of available primers, and that improved primer pairs enable to estimate archaeal diversity more accurately.}, language = {en} } @article{GreberPolatFlentjeetal.2019, author = {Greber, Johannes and Polat, B{\"u}lent and Flentje, Michael and Bratengeier, Klaus}, title = {Properties of the anisotropy of dose contributions: A planning study on prostate cases}, series = {Medical Physics}, volume = {46}, journal = {Medical Physics}, doi = {10.1002/mp.13308}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228237}, pages = {419-425}, year = {2019}, abstract = {Purpose To characterize the static properties of the anisotropy of dose contributions for different treatment techniques on real patient data (prostate cases). From this, we aim to define a class of treatment techniques with invariant anisotropy distribution carrying information of target coverage and organ-at-risk (OAR) sparing. The anisotropy presumably is a helpful quantity for plan adaptation problems. Methods The anisotropy field is analyzed for different intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques for a total of ten planning CTs of prostate cases. Primary irradiation directions ranged from 5 to 15. The uniqueness of anisotropy was explored: In particular, the anisotropy distribution inside the planning treatment volume (PTV) and in its vicinity was investigated. Furthermore, deviations of the anisotropy under beam rotations were explored by direct plan comparison as an indicating the susceptibility of each planned technique to changes in the geometric plan configuration. In addition, plan comparisons enabled the categorization of treatment techniques in terms of their anisotropy distribution. Results The anisotropy profile inside the PTV and in the transition between OAR and PTV is independent of the treatment technique as long as a sufficient number of beams contribute to the dose distribution. Techniques with multiple beams constitute a class of almost identical and technique-independent anisotropy distribution. For this class of techniques, substructures of the anisotropy are particularly pronounced in the PTV, thus offering good options for applying adaptation rules. Additionally, the techniques forming the mentioned class fortunately allow a better OAR sparing at constant PTV coverage. Besides the characterization of the distribution, a pairwise plan comparison reveals each technique's susceptibility to deviations which decreases for an increasing number of primary irradiation directions. Conclusions Techniques using many irradiation directions form a class of almost identical anisotropy distributions which are assumed to provide a basis for improved adaptation procedures. Encouragingly, these techniques deliver quite invariant anisotropy distributions with respect to rotations correlated with good plan qualities than techniques using few gantry angles. The following will be the next steps toward anisotropy-based adaptation: first, the quantification of anisotropy regarding organ deformations; and second, establishing the interrelation between the anisotropy and beam shaping.}, language = {en} } @article{MirzaVainshteinDiRonzaetal.2019, author = {Mirza, Myriam and Vainshtein, Anna and DiRonza, Alberto and Chandrachud, Uma and Haslett, Luke J. and Palmieri, Michela and Storch, Stephan and Groh, Janos and Dobzinski, Niv and Napolitano, Gennaro and Schmidtke, Carolin and Kerkovich, Danielle M.}, title = {The CLN3 gene and protein: What we know}, series = {Molecular Genetics \& Genomic Medicine}, volume = {7}, journal = {Molecular Genetics \& Genomic Medicine}, doi = {10.1002/mgg3.859}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224138}, year = {2019}, abstract = {Background One of the most important steps taken by Beyond Batten Disease Foundation in our quest to cure juvenile Batten (CLN3) disease is to understand the State of the Science. We believe that a strong understanding of where we are in our experimental understanding of the CLN3 gene, its regulation, gene product, protein structure, tissue distribution, biomarker use, and pathological responses to its deficiency, lays the groundwork for determining therapeutic action plans. Objectives To present an unbiased comprehensive reference tool of the experimental understanding of the CLN3 gene and gene product of the same name. Methods BBDF compiled all of the available CLN3 gene and protein data from biological databases, repositories of federally and privately funded projects, patent and trademark offices, science and technology journals, industrial drug and pipeline reports as well as clinical trial reports and with painstaking precision, validated the information together with experts in Batten disease, lysosomal storage disease, lysosome/endosome biology. Results The finished product is an indexed review of the CLN3 gene and protein which is not limited in page size or number of references, references all available primary experiments, and does not draw conclusions for the reader. Conclusions Revisiting the experimental history of a target gene and its product ensures that inaccuracies and contradictions come to light, long-held beliefs and assumptions continue to be challenged, and information that was previously deemed inconsequential gets a second look. Compiling the information into one manuscript with all appropriate primary references provides quick clues to which studies have been completed under which conditions and what information has been reported. This compendium does not seek to replace original articles or subtopic reviews but provides an historical roadmap to completed works.}, language = {en} } @article{ArlottiPalmisanoMinafraetal.2019, author = {Arlotti, Mattia and Palmisano, Chiara and Minafra, Brigida and Todisco, Massimiliano and Pacchetti, Claudio and Canessa, Andrea and Pozzi, Nicol{\´o} G. and Cilia, Roberto and Prenassi, Marco and Marceglia, Sara and Priori, Alberto and Rampini, Paolo and Barbieri, Sergio and Servello, Domenico and Volkmann, Jens and Pezzoli, Gianni and Isaias, Ioannis U.}, title = {Monitoring subthalamic oscillations for 24 hours in a freely moving Parkinson's disease patient}, series = {Movement Disorders}, volume = {34}, journal = {Movement Disorders}, doi = {10.1002/mds.27657}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221249}, pages = {757-759}, year = {2019}, abstract = {No abstract available}, language = {en} } @article{CalderonPenaSuarezetal.2019, author = {Calderon, Dayana and Pe{\~n}a, Luis and Suarez, Ang{\´e}lica and Villamil, Carolina and Ramirez-Rojas, Adan and Anzola, Juan M. and Garc{\´i}a-Betancur, Juan C. and Cepeda, Martha L. and Uribe, Daniel and Del Portillo, Patricia and Mongui, Alvaro}, title = {Recovery and functional validation of hidden soil enzymes in metagenomic libraries}, series = {MicrobiologyOpen}, volume = {8}, journal = {MicrobiologyOpen}, doi = {10.1002/mbo3.572}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222016}, year = {2019}, abstract = {The vast microbial diversity on the planet represents an invaluable source for identifying novel activities with potential industrial and therapeutic application. In this regard, metagenomics has emerged as a group of strategies that have significantly facilitated the analysis of DNA from multiple environments and has expanded the limits of known microbial diversity. However, the functional characterization of enzymes, metabolites, and products encoded by diverse microbial genomes is limited by the inefficient heterologous expression of foreign genes. We have implemented a pipeline that combines NGS and Sanger sequencing as a way to identify fosmids within metagenomic libraries. This strategy facilitated the identification of putative proteins, subcloning of targeted genes and preliminary characterization of selected proteins. Overall, the in silico approach followed by the experimental validation allowed us to efficiently recover the activity of previously hidden enzymes derived from agricultural soil samples. Therefore, the methodology workflow described herein can be applied to recover activities encoded by environmental DNA from multiple sources.}, language = {en} } @article{HettichSchierjottRammetal.2019, author = {Hettich, Georg and Schierjott, Ronja A. and Ramm, Heiko and Graichen, Heiko and Jansson, Volkmar and Rudert, Maximilian and Traina, Francesco and Grupp, Thomas M.}, title = {Method for quantitative assessment of acetabular bone defects}, series = {Journal of Orthopaedic Research}, volume = {37}, journal = {Journal of Orthopaedic Research}, doi = {10.1002/jor.24165}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320226}, pages = {181-189}, year = {2019}, abstract = {The objective of the study was to suggest a novel quantitative assessment of acetabular bone defects based on a statistical shape model, validate the method, and present preliminary results. Two exemplary CT-data sets with acetabular bone defects were segmented to obtain a solid model of each defect pelvis. The pathological areas around the acetabulum were excluded and a statistical shape model was fitted to the remaining healthy bone structures. The excluded areas were extrapolated such that a solid model of the native pelvis per specimen resulted (i.e., each pelvis without defect). The validity of the reconstruction was tested by a leave-one-out study. Validation results showed median reconstruction errors of 3.0 mm for center of rotation, 1.7 mm for acetabulum diameter, 2.1° for inclination, 2.5° for anteversion, and 3.3 mm3 for bone volume around the acetabulum. By applying Boolean operations on the solid models of defect and native pelvis, bone loss and bone formation in four different sectors were assessed. For both analyzed specimens, bone loss and bone formation per sector were calculated and were consistent with the visual impression. In specimen_1 bone loss was predominant in the medial wall (10.8 ml; 79\%), in specimen_2 in the posterior column (15.6 ml; 46\%). This study showed the feasibility of a quantitative assessment of acetabular bone defects using a statistical shape model-based reconstruction method. Validation results showed acceptable reconstruction accuracy, also when less healthy bone remains. The method could potentially be used for implant development, pre-clinical testing, pre-operative planning, and intra-operative navigation. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 9999:1-9, 2018.}, language = {en} } @article{KasparOttHertigKasparetal.2019, author = {Kaspar-Ott, Irena and Hertig, Elke and Kaspar, Severin and Pollinger, Felix and Ring, Christoph and Paeth, Heiko and Jacobeit, Jucundus}, title = {Weights for general circulation models from CMIP3/CMIP5 in a statistical downscaling framework and the impact on future Mediterranean precipitation}, series = {The International Journal of Climatology}, volume = {39}, journal = {The International Journal of Climatology}, doi = {10.1002/joc.6045}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325628}, pages = {3639-3654}, year = {2019}, abstract = {This study investigates the projected precipitation changes of the 21st century in the Mediterranean area with a model ensemble of all available CMIP3 and CMIP5 data based on four different scenarios. The large spread of simulated precipitation change signals underlines the need of an evaluation of the individual general circulation models in order to give higher weights to better and lower weights to worse performing models. The models' spread comprises part of the internal climate variability, but is also due to the differing skills of the circulation models. The uncertainty resulting from the latter is the aim of our weighting approach. Each weight is based on the skill to simulate key predictor variables in context of large and medium scale atmospheric circulation patterns within a statistical downscaling framework for the Mediterranean precipitation. Therefore, geopotential heights, sea level pressure, atmospheric layer thickness, horizontal wind components and humidity data at several atmospheric levels are considered. The novelty of this metric consists in avoiding the use of the precipitation data by itself for the weighting process, as state-of-the-art models still have major deficits in simulating precipitation. The application of the weights on the downscaled precipitation changes leads to more reliable and precise change signals in some Mediterranean sub-regions and seasons. The model weights differ between sub-regions and seasons, however, a clear sequence from better to worse models for the representation of precipitation in the Mediterranean area becomes apparent.}, language = {en} }