TY  - JOUR
A1  - Böhm, Jennifer
A1  - Scherzer, Sönke
A1  - Krol, Elzbieta
A1  - Kreuzer, Ines
A1  - von Meyer, Katharina
A1  - Lorey, Christian
A1  - Mueller, Thomas D.
A1  - Shabala, Lana
A1  - Monte, Isabel
A1  - Salano, Roberto
A1  - Al-Rasheid, Khaled A. S.
A1  - Rennenberg, Heinz
A1  - Shabala, Sergey
A1  - Neher, Erwin
A1  - Hedrich, Rainer
T1  - The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake
JF  - Current Biology
N2  - Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na+-rich animal and nutrition for the plant.
KW  - Venusfliegenfalle
KW  - Dionaea muscipula
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128054
VL  - 26
IS  - 3
ER  - 
TY  - JOUR
A1  - Böhm, Jennifer
A1  - Scherzer, Sönke
A1  - Krol, Elzbieta
A1  - Kreuzer, Ines
A1  - von Meyer, Katharina
A1  - Lorey, Christian
A1  - Mueller, Thomas D.
A1  - Shabala, Lana
A1  - Monte, Isabel
A1  - Solano, Roberto
A1  - Al-Rasheid, Khaled A. S.
A1  - Rennenberg, Heinz
A1  - Shabala, Sergey
A1  - Neher, Erwin
A1  - Hedrich, Rainer
T1  - The Venus flytrap Dionaea muscipula counts prey-induced action potentials to induce sodium uptake
JF  - Current Biology
N2  - Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na\(^+\)-rich animal and nutrition for the plant.
KW  - jasmonic acid biosynthesis
KW  - gene expression
KW  - signal transduction
KW  - transporters
KW  - Arabidopsis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190870
VL  - 26
IS  - 3
ER  - 
TY  - JOUR
A1  - Boschert, V.
A1  - Frisch, C.
A1  - Back, J. W.
A1  - van Pee,, K.
A1  - Weidauer, S. E.
A1  - Muth, E.-M.
A1  - Schmieder, P.
A1  - Beerbaum, M.
A1  - Knappik, A.
A1  - Timmerman, P.
A1  - Mueller, T. D.
T1  - The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6
JF  - Open Biology
N2  - The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure–function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis.
KW  - phage display
KW  - Wnt signalling
KW  - sclerostin
KW  - neutralizing antibody
KW  - osteoporosis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177925
VL  - 6
ER  - 
TY  - JOUR
A1  - Mueller, A.
A1  - Stoetter, L.
A1  - Kalluvya, S.
A1  - Stich, A.
A1  - Majinge, C.
A1  - Weissbrich, B.
A1  - Kasang, C.
T1  - Prevalence of hepatitis B virus infection among health care workers in a tertiary hospital in Tanzania
JF  - BMC Infectious Diseases
N2  - Background: Sub-Saharan Africa has a high prevalence of hepatitis B virus (HBV) infections. Health care workers (HCWs) are at high risk of contracting HBV infection through their occupation. Vaccination of HCWs against HBV is standard practice in many countries, but is often not implemented in resource-poor settings. We aimed with this cross-sectional study to determine HBV prevalence, HCW vaccination status, and the risk factors for HCWs contracting HBV infection in Tanzania. 
Methods: We enrolled 600 HCWs from a tertiary Tanzanian hospital. Their demographics, medical histories, HBV vaccination details and risk factors for contracting blood-borne infections were collected using a standardized questionnaire. Serum samples were tested for HBV and hepatitis C virus (HCV) markers by ELISA techniques, PCR and an anti-HBs rapid test. HCWs were divided in two subgroups: those at risk of contracting HBV (rHCW 79.2 %) via exposure to potentially infectious materials, and those considered not at risk of contracting HBV (nrHCW, 20.8 %). Results: The overall prevalence of chronic HBV infection (HBsAg+, anti-HBc+, anti-HBs-) was 7.0 % (42/598). Chronic HBV infection was found in 7.4 % of rHCW versus 5.6 % of nrHCW(p-value = 0.484). HCWs susceptible to HBV (HBsAg-, anti-HBc-, anti-HBs-) comprised 31.3 %. HBV immunity achieved either by healed HBV infection (HBsAg-, anti-HBc+, anti-HBs+) or by vaccination (HBsAg-, anti-HBc-, anti-HBs+) comprised 36.5 % and 20.2 %, respectively. 4.8 % of participants had indeterminate results (HBsAg-, anti-HBc+, anti-HBc-IgM-, anti-HBs-). Only 77.1 % of HCWs who received a full vaccination course had an anti-HBs titer > 10 ml/U. An anti-HBs point-of-care test was 80.7 % sensitive and 96.9 % specific. There was a significantly higher risk for contracting HBV (anti-HBc+) among those HCW at occupational risk (rHCW) of older age (odds ratios (OR) in rHCW 3.297, p < 0.0001 vs. nrHCW 1.385, p = 0.606) and among those HCW being employed more than 11 years (OR 2.51, p < 0.0001***). HCV prevalence was low (HCV antibodies 1.2 % and HCV-RNA 0.3 %). 
Conclusions: Chronic HBV infection is common among Tanzanian HCWs. One third of HCWs were susceptible to HBV infection, highlighting the need for vaccination. Due to high prevalence of naturally acquired immunity against HBV pre-testing might be a useful tool to identify susceptible individuals.
KW  - hepatitis C virus
KW  - point-of-care test
KW  - human-immunodeficiency-virus
KW  - C virus
KW  - seroprevalence
KW  - syphilis
KW  - vaccine
KW  - Uganda
KW  - blood
KW  - hepatitis B virus
KW  - health care workers
KW  - Tanzania
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141786
VL  - 15
IS  - 386
ER  - 
TY  - JOUR
A1  - Keller, Andreas
A1  - Leidinger, Petra
A1  - Vogel, Britta
A1  - Backes, Christina
A1  - ElSharawy, Abdou
A1  - Galata, Valentina
A1  - Mueller, Sabine C.
A1  - Marquart, Sabine
A1  - Schrauder, Michael G.
A1  - Strick, Reiner
A1  - Bauer, Andrea
A1  - Wischhusen, Jörg
A1  - Beier, Markus
A1  - Kohlhaas, Jochen
A1  - Katus, Hugo A.
A1  - Hoheisel, Jörg
A1  - Franke, Andre
A1  - Meder, Benjamin
A1  - Meese, Eckart
T1  - miRNAs can be generally associated with human pathologies as exemplified for miR-144*
JF  - BMC MEDICINE
N2  - Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. 
Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. 
Results: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 ( 95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. 
Conclusions: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.
KW  - peripheral blood
KW  - microna profiles
KW  - disease
KW  - signature
KW  - expression
KW  - miRNA
KW  - microarray
KW  - biomarker
KW  - bioinformatics
KW  - lung-cancer
KW  - multiple sclerosis
KW  - gene
KW  - serum
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114349
SN  - 1741-7015
VL  - 12
ER  - 
TY  - JOUR
A1  - Elmaidomy, Abeer H.
A1  - Mohammed, Rabab
A1  - Hassan, Hossam M.
A1  - Owis, Asmaa I.
A1  - Rateb, Mostafa E.
A1  - Khanfar, Mohammad A.
A1  - Krischke, Markus
A1  - Mueller, Martin J.
A1  - Abdelmohsen, Usama Ramadan
T1  - Metabolomic profiling and cytotoxic tetrahydrofurofuran lignans investigations from Premna odorata Blanco
JF  - Metabolites
N2  - Metabolomic profiling of different Premna odorata Blanco (Lamiaceae) organs, bark, wood, young stems, flowers, and fruits dereplicated 20, 20, 10, 20, and 20 compounds, respectively, using LC–HRESIMS. The identified metabolites (1–34) belonged to different chemical classes, including iridoids, flavones, phenyl ethanoids, and lignans. A phytochemical investigation of P. odorata bark afforded one new tetrahydrofurofuran lignan, 4β-hydroxyasarinin 35, along with fourteen known compounds. The structure of the new compound was confirmed using extensive 1D and 2D NMR, and HRESIMS analyses. A cytotoxic investigation of compounds 35–38 against the HL-60, HT-29, and MCF-7 cancer cell lines, using the MTT assay showed that compound 35 had cytotoxic effects against HL-60 and MCF-7 with IC50 values of 2.7 and 4.2 µg/mL, respectively. A pharmacophore map of compounds 35 showed two hydrogen bond acceptor (HBA) aligning the phenoxy oxygen atoms of benzodioxole moieties, two aromatic ring features vectored on the two phenyl rings, one hydrogen bond donor (HBD) feature aligning the central hydroxyl group and thirteen exclusion spheres which limit the boundaries of sterically inaccessible regions of the target’s active site.
KW  - Premna
KW  - lignan
KW  - metabolomic
KW  - cytotoxic
KW  - pharmacophore map
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193187
SN  - 2218-1989
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Albert, A.
A1  - André, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Avgitas, T.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Basa, S.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Bouwhuis, M.C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Busto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Celli, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coleiro, A.
A1  - Coniglione, R.
A1  - Costantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Deschamps, A.
A1  - De Bonis, G.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Drouhin, D.
A1  - Eberl, T.
A1  - El Bojaddaini, I.
A1  - Elsässer, D.
A1  - Enzenhöfer, A.
A1  - Fehn, K.
A1  - Felis, I.
A1  - Fusco, L.A.
A1  - Galatà, S.
A1  - Gay, P.
A1  - Geißelsöder, S.
A1  - Geyer, K.
A1  - Giordano, V.
A1  - Gleixner, A.
A1  - Glotin, H.
A1  - Gracia-Ruiz, R.
A1  - Graf, K.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Heijboer, A.J.
A1  - Hello, Y.
A1  - Hernández-Rey, J.J.
A1  - Hößl, J.
A1  - Hofestädt, J.
A1  - Hugon, C.
A1  - Illuminati, G.
A1  - James, C.W.
A1  - de Jong, M.
A1  - Jongen, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Katz, U.
A1  - Kießling, D.
A1  - Kouchner, A.
A1  - Kreter, M.
A1  - Kreykenbohm, I.
A1  - Kulikovskiy, V.
A1  - Lachaud, C.
A1  - Lahmann, R.
A1  - Lefèvre, D.
A1  - Leonora, E.
A1  - Loucatos, S.
A1  - Marcelin, M.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Martínez-Mora, J.A.
A1  - Mathieu, A.
A1  - Melis, K.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Moussa, A.
A1  - Mueller, C.
A1  - Nezri, E.
A1  - Pavalas, G.E.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Piattelli, P.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Racca, C.
A1  - Riccobene, G.
A1  - Roensch, K.
A1  - Saldaña, M.
A1  - Samtleben, D.F.E.
A1  - Sánchez-Losa, A.
A1  - Sanguineti, M.
A1  - Sapienza, P.
A1  - Schnabel, J.
A1  - Schüssler, F.
A1  - Seitz, T.
A1  - Sieger, C.
A1  - Spurio, M.
A1  - Stolarczyk, Th.
A1  - Taiuti, M.
A1  - Tönnis, C.
A1  - Trovato, A.
A1  - Tselengidou, M.
A1  - Turpin, D.
A1  - Vallage, B.
A1  - Vallée, C.
A1  - Van Elewyck, V.
A1  - Vivolo, D.
A1  - Wagner, S.
A1  - Wilms, J.
A1  - Zornoza, J.D.
A1  - Zúñiga, J.
T1  - Limits on dark matter annihilation in the sun using the ANTARES neutrino telescope
JF  - Physics Letters B
N2  - A search for muon neutrinos originating from dark matter annihilations in the Sun is performed using the data recorded by the ANTARES neutrino telescope from 2007 to 2012. In order to obtain the best possible sensitivities to dark matter signals, an optimisation of the event selection criteria is performed taking into account the background of atmospheric muons, atmospheric neutrinos and the energy spectra of the expected neutrino signals. No significant excess over the background is observed and 90% C.L. upper limits on the neutrino flux, the spin-dependent and spin-independent WIMP-nucleon cross-sections are derived for WIMP masses ranging from 50 GeV to 5 TeV for the annihilation channels WIMP + WIMP→ b\(\overline{b}\), W\(^{+}\)W\(^{−}\) and τ\(^{+}\)τ\(^{−}\).
KW  - dark matter
KW  - WIMP
KW  - neutralino
KW  - indirect detection
KW  - neutrino telescope
KW  - sun
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166642
VL  - 759
ER  - 
TY  - JOUR
A1  - Diestel, Uschi
A1  - Resch, Marcus
A1  - Meinhardt, Kathrin
A1  - Weiler, Sigrid
A1  - Hellmann, Tina V.
A1  - Mueller, Thomas D.
A1  - Nickel, Joachim
A1  - Eichler, Jutta
A1  - Muller, Yves A.
T1  - Identification of a Novel TGF-beta-Binding Site in the Zona Pellucida C-terminal (ZP-C) Domain of TGF-\(\beta\)-Receptor-3 (TGFR-3)
JF  - PLoS ONE
N2  - The zona pellucida (ZP) domain is present in extracellular proteins such as the zona pellucida proteins and tectorins and participates in the formation of polymeric protein networks. However, the ZP domain also occurs in the cytokine signaling co-receptor transforming growth factor beta (TGF-\(\beta\)) receptor type 3 (TGFR-3, also known as betaglycan) where it contributes to cytokine ligand recognition. Currently it is unclear how the ZP domain architecture enables this dual functionality. Here, we identify a novel major TGF-beta-binding site in the FG loop of the C-terminal subdomain of the murine TGFR-3 ZP domain (ZP-C) using protein crystallography, limited proteolysis experiments, surface plasmon resonance measurements and synthetic peptides. In the murine 2.7 angstrom crystal structure that we are presenting here, the FG-loop is disordered, however, well-ordered in a recently reported homologous rat ZP-C structure. Surprisingly, the adjacent external hydrophobic patch (EHP) segment is registered differently in the rat and murine structures suggesting that this segment only loosely associates with the remaining ZP-C fold. Such a flexible and temporarily-modulated association of the EHP segment with the ZP domain has been proposed to control the polymerization of ZP domain-containing proteins. Our findings suggest that this flexibility also extends to the ZP domain of TGFR-3 and might facilitate co-receptor ligand interaction and presentation via the adjacent FG-loop. This hints that a similar C-terminal region of the ZP domain architecture possibly regulates both the polymerization of extracellular matrix proteins and cytokine ligand recognition of TGFR-3.
KW  - coreceptor
KW  - receptor type III
KW  - growth factor beta
KW  - ligand binding
KW  - betaglycan
KW  - proteins
KW  - mutagenesis
KW  - polymerization
KW  - glycoprotein
KW  - superfamily
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130904
VL  - 8
IS  - 6
ER  - 
TY  - JOUR
A1  - Krauss, Jochen
A1  - Vikuk, Veronika
A1  - Young, Carolyn A.
A1  - Krischke, Markus
A1  - Mueller, Martin J.
A1  - Baerenfaller, Katja
T1  - Epichloë endophyte infection rates and alkaloid content in commercially available grass seed mixtures in Europe
JF  - Microorganisms
N2  - Fungal endophytes of the genus Epichloë live symbiotically in cool season grass species and can produce alkaloids toxic to insects and vertebrates, yet reports of intoxication of grazing animals have been rare in Europe in contrast to overseas. However, due to the beneficial resistance traits observed in Epichloë infected grasses, the inclusion of Epichloë in seed mixtures might become increasingly advantageous. Despite the toxicity of fungal alkaloids, European seed mixtures are rarely tested for Epichloë infection and their infection status is unknown for consumers. In this study, we tested 24 commercially available seed mixtures for their infection rates with Epichloë endophytes and measured the concentrations of the alkaloids ergovaline, lolitrem B, paxilline, and peramine. We detected Epichloë infections in six seed mixtures, and four contained vertebrate and insect toxic alkaloids typical for Epichloë festucae var. lolii infecting Lolium perenne. As Epichloë infected seed mixtures can harm livestock, when infected grasses become dominant in the seeded grasslands, we recommend seed producers to test and communicate Epichloë infection status or avoiding Epichloë infected seed mixtures.
KW  - Epichloë spp.
KW  - grass endophytes
KW  - cool-season grass species
KW  - infection rates
KW  - alkaloids
KW  - toxicity
KW  - livestock
KW  - horses
KW  - Lolium perenne
KW  - perennial ryegrass
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203323
SN  - 2076-2607
VL  - 8
IS  - 4
ER  - 
TY  - JOUR
A1  - Krauss, Jochen
A1  - Vikuk, Veronika
A1  - Young, Carolyn A.
A1  - Krischke, Markus
A1  - Mueller, Martin J.
A1  - Baerenfaller, Katja
T1  - Correction: Krauss, J., et al. Epichloë endophyte infection rates and alkaloid content in commercially available grass seed mixtures in Europe. Microorganisms 2020, 8, 498
JF  - Microorganisms
N2  - No abstract available.
KW  - Epichloë
KW  - endophyte
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216254
SN  - 2076-2607
VL  - 8
IS  - 10
ER  -