Manfred Kraus - Academia.edu (original) (raw)

Papers by Manfred Kraus

Research paper thumbnail of Identification of sawflies and horntails (Hymenoptera, ‘Symphyta’) through DNA barcodes: successes and caveats

Molecular Ecology Resources, 2016

The 'Symphyta&amp... more The 'Symphyta' is a paraphyletic assemblage at the base of the order Hymenoptera, comprising 14 families and about 8750 species. All have phytophagous larvae, except for the Orussidae, which are parasitoids. This study presents and evaluates the results of DNA barcoding of approximately 5360 specimens of 'Symphyta', mainly adults, and 4362 sequences covering 1037 species were deemed of suitable quality for inclusion in the analysis. All extant families are represented, except for the Anaxyelidae. The majority of species and specimens are from Europe, but approximately 38% of the species and 13% of the specimens are of non-European origin. The utility of barcoding for species identification and taxonomy of 'Symphyta' is discussed on the basis of examples from each of the included families. A significant level of cryptic species diversity was apparent in many groups. Other attractive applications include the identification of immature stages without the need to rear them, community analyses based on metabarcoding of bulk samples and association of the sexes of adults.

Research paper thumbnail of I PDK1 Attenuation Fails to Prevent Tumor Formation in PTEN-Deficient Transgenic Mouse Models

Research paper thumbnail of Survival of Resting Mature B Lymphocytes Depends on BCR Signaling via the Ig¿/ß Heterodimer

Cell, 2004

We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR express... more We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR expression in mature B cells through Ig-heavy chain deletion results in apoptosis of these cells. This led to the hypothesis that survival signals from the BCR are vital for mature B cells. Here, we test two critical assumptions of this model. First, we demonstrate loss of mature B cells upon induced mutation of a signaling module of the BCR, not precluding BCR surface expression. Second, we show that the cells are also lost upon BCR inactivation in the absence of an exogenous inducer like interferon, excluding that cell death depends on previous cellular activation by the latter. Kinetic data demonstrate that BCR-less mature B cells have a severely reduced lifespan, with a half-life of 3-6 days. Together these results establish that BCR signaling is required to keep resting mature B cells alive in vivo.

Research paper thumbnail of Survival of Resting Mature B Lymphocytes Depends on BCR Signaling via the Iga/� Heterodimer

Cell, 2004

We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR express... more We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR expression in mature B cells through Ig-heavy chain deletion results in apoptosis of these cells. This led to the hypothesis that survival signals from the BCR are vital for mature B cells. Here, we test two critical assumptions of this model. First, we demonstrate loss of mature B cells upon induced mutation of a signaling module of the BCR, not precluding BCR surface expression. Second, we show that the cells are also lost upon BCR inactivation in the absence of an exogenous inducer like interferon, excluding that cell death depends on previous cellular activation by the latter. Kinetic data demonstrate that BCR-less mature B cells have a severely reduced lifespan, with a half-life of 3-6 days. Together these results establish that BCR signaling is required to keep resting mature B cells alive in vivo.

Research paper thumbnail of Interference with Immunoglobulin (Ig) Immunoreceptor Tyrosine-Based Activation Motif (Itam) Phosphorylation Modulates or Blocks B Cell Development, Depending on the Availability of an Ig Cytoplasmic Tail

J Exp Med, 2001

To determine the function of immunoglobulin (Ig) ␣ immunoreceptor tyrosine-based activation motif... more To determine the function of immunoglobulin (Ig) ␣ immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation, we generated mice in which Ig ␣ ITAM tyrosines were replaced by phenylalanines ( Ig ␣ FF/FF ). Ig ␣ FF/FF mice had a specific reduction of B1 and marginal zone B cells, whereas B2 cell development appeared to be normal, except that 1 light chain usage was increased. The mutants responded less efficiently to T cell-dependent antigens, whereas T cell-independent responses were unaffected. Upon B cell receptor ligation, the cells exhibited heightened calcium flux, weaker Lyn and Syk tyrosine phosphorylation, and phosphorylation of Ig ␣ non-ITAM tyrosines. Strikingly, when the Ig ␣ ITAM mutation was combined with a truncation of Ig ␤ , B cell development was completely blocked at the pro-B cell stage, indicating a crucial role of ITAM phosphorylation in B cell development.

Research paper thumbnail of Unterordnung Symphyta - Planzenwespen

Der Verlag und die Autoren haben alle Sorgfalt walten lassen, um vollständige und akkurate Inform... more Der Verlag und die Autoren haben alle Sorgfalt walten lassen, um vollständige und akkurate Informationen in diesem Buch zu publizieren. Der Verlag übernimmt weder Garantie noch die juristische Verantwortung oder irgendeine Haftung für die Nutzung dieser Informationen, für deren Wirtschaftlichkeit oder fehlerfreie Funktion für einen bestimmten Zweck. Der Verlag übernimmt keine Gewähr dafür, dass die beschriebenen Verfahren, Programme usw. frei von Schutzrechten Dritter sind. Der Verlag hat sich bemüht, sämtliche Rechteinhaber von Abbildungen zu ermitteln. Sollte dem Verlag gegenüber dennoch der Nachweis der Rechtsinhaberschaft geführt werden, wird das branchenübliche Honorar gezahlt. Bibliograflsche Information Der Deutschen Bibliothek Die Deutsche Bibliothek verzeichnet diese Publikation in der Deutschen Nationalbibliografie; detaillierte bibliografische Daten sind im Internet über http://dnb.ddb.de abrufbar. Alle Rechte vorbehalten 10. Auflage 2005

Research paper thumbnail of Contribution to the knowledge of sawfly fauna (Hymenoptera, Symphyta) of the Low Tatras National Park in Central Slovakia

k poznaniu fauny hrubopásych (Hymenoptera, Symphyta) Národného parku Nízke Tatry Abstrakt: Počas ... more k poznaniu fauny hrubopásych (Hymenoptera, Symphyta) Národného parku Nízke Tatry Abstrakt: Počas deviateho medzinárodného pracovného stretnutia špecialistov na hrubopáse blanokrídlovce (Hymenoptera, Symphyta) v júni 2005 bol vykonaný faunistický prieskum hrubopásych na viacerých lokalitách Národného parku Nízke Tatry. Celkovo bolo zaznamenaných 200 druhov a osem čeľadí hrubopásych. Ďalších dvanásť taxónov nebolo identifikovaných do druhu. Dolerus altivolus, D. hibernicus, Eriocampa dorpatica, Euura hastatae, Fenella monilicornis, Nematus yokohamensis tavastiensis, Pachynematus clibrichellus, Phyllocolpa excavata, P. polita, P. rolleri, Pontania gallarum, P. virilis, Pristiphora breadalbanensis, P. coactula a Tenthredo ignobilis boli zistené na Slovensku po prvýkrát. Významný počet faunisticky zaujímavých nálezov naznačuje vysokú zachovalosť študovaných prírodných stanovíšť v širšom okolí Demänovskej a Jánskej doliny, Svarína a v Národnej prírodnej rezervácii Turková.

Research paper thumbnail of Die invasive Zick-Zack-Ulmenblattwespe Aproceros leucopoda Takeuchi, 1939 (Hym., Argidae) in Deutschland

Research paper thumbnail of The nominal taxa described by K. Warncke and their types (Insecta, Hymenoptera, Apoidea)

We present a catalogue of all new taxa of bees (Insecta: Hymenoptera, Apoidea) which were describ... more We present a catalogue of all new taxa of bees (Insecta: Hymenoptera, Apoidea) which were described by Klaus Warncke. Between 1965 and 1993 he described 57 new taxa of the genus group and 887 new taxa of the species group, which are listed here with their original citation. Conformity of the type series with the original description was verified, the orthography of few taxa was corrected according to the ICZN (1985). The purpose of this paper is to summarize and to allow easy access to Warncke's work. The collection of Warncke is preserved at the Oberösterreichisches Landesmuseum in Linz (Austria), the parasitic genera are deposited in the private collection of Maximilian Schwarz (Ansfelden, Austria).

Research paper thumbnail of The Pim Kinase Inhibitor AZD1208 Enhances Apoptosis Induction By Clinically Active FLT3 Inhibitors in FLT3-ITD Acute Myeloid Leukemia Cells in Vitro and in Vivo through Synergistic Downregulation of Mcl-1 and of Bcl-xL

Research paper thumbnail of Kommentare zur Biologie, Verbreitung und Gefährdung der Pflanzenwespen Deutschlands (Hymenoptera, Symphyta)

Page 1. Kommentare zur Biologie, Verbreitung und Gefährdung der Pflanzenwespen Deutschlands (Hyme... more Page 1. Kommentare zur Biologie, Verbreitung und Gefährdung der Pflanzenwespen Deutschlands (Hymenoptera, Symphyta) Andreas TAEGER, Ewald ALTENHOFER, Stephan M. BLANK, Ewald JANSEN, Manfred KRAUS, Hubert PSCHORN-WALCHER, Carsten RITZAU ...

Research paper thumbnail of Rote Liste der Pflanzenwespen (Hymenoptera: Symphyta)

Research paper thumbnail of Symphyta. In: Dathe, H. H.; Taeger, A.; Blank, S. M. (Hrsg.): Verzeichnis der Hautflügler Deutschlands (Fauna Germanica 4)

Research paper thumbnail of Orussus smithi sp. n. and Notes on Other West Palaearctic Orussidae (Hymenoptera)

Research paper thumbnail of Unterordnung Symphyta - Pflanzenwespen

Research paper thumbnail of Rote Liste und Gesamtartenliste der Pflanzenwespen (Hymenoptera: Symphyta) Deutschlands. Stand März 2011

Liston, A.D.; Jansen, E.; Blank, S.M.; Kraus, M. & Taeger, A. (2011): Rote Liste und Gesamtartenl... more Liston, A.D.; Jansen, E.; Blank, S.M.; Kraus, M. & Taeger, A. (2011): Rote Liste und Gesamtartenliste der Pflanzenwespen (Hymenoptera: Symphyta) Deutschlands. -In: Binot-Hafke, M.; Balzer, S.; Becker, N.; Gruttke, H.; Haupt, H.; Hofbauer, N.; Ludwig, G.; Matzke-Hajek, G. & Strauch, M. (Red.): Rote Liste gefährdeter Tiere, Pflanzen und Pilze Deutschlands. Band 3: Wirbellose Tiere (Teil 1). -Münster (Landwirtschaftsverlag). -Naturschutz und Biologische Vielfalt 70 (3): 491-556. Die Rote Liste gefährdeter Tiere, Pflanzen und Pilze Deutschlands, Band 3: Wirbellose Tiere (Teil 1) (ISBN 978-3-7843-5231-2) ist zu beziehen über BfN-Schriftenvertrieb -Leserserviceim Landwirtschaftsverlag GmbH 48084 Münster

Research paper thumbnail of Hymenoptera-Hautflügler

Research paper thumbnail of Pathway-Based Identification of Biomarkers for Targeted Therapeutics: Personalized Oncology with PI3K Pathway Inhibitors

Science Translational Medicine, 2010

Although we have made great progress in understanding the complex genetic alterations that underl... more Although we have made great progress in understanding the complex genetic alterations that underlie human cancer, it has proven difficult to identify which molecularly targeted therapeutics will benefit which patients. Drug-specific modulation of oncogenic signaling pathways in specific patient subpopulations can predict responsiveness to targeted therapy. Here, we report a pathway-based phosphoprofiling approach to identify and quantify clinically relevant, drug-specific biomarkers for phosphatidylinositol 3-kinase (PI3K) pathway inhibitors that target AKT, phosphoinositide-dependent kinase 1 (PDK1), and PI3K-mammalian target of rapamycin (mTOR). We quantified 375 nonredundant PI3K pathway-relevant phosphopeptides, all containing AKT, PDK1, or mitogen-activated protein kinase substrate recognition motifs. Of these phosphopeptides, 71 were drug-regulated, 11 of them by all three inhibitors. Drug-modulated phosphoproteins were enriched for involvement in cytoskeletal reorganization (filamin, stathmin, dynamin, PAK4, and PTPN14), vesicle transport (LARP1, VPS13D, and SLC20A1), and protein translation (S6RP and PRAS40). We then generated phosphospecific antibodies against selected, drug-regulated phosphorylation sites that would be suitable as biomarker tools for PI3K pathway inhibitors. As proof of concept, we show clinical translation feasibility for an antibody against phospho-PRAS40(Thr246). Evaluation of binding of this antibody in human cancer cell lines, a PTEN (phosphatase and tensin homolog deleted from chromosome 10)-deficient mouse prostate tumor model, and triple-negative breast tumor tissues showed that phospho-PRAS40(Thr246) positively correlates with PI3K pathway activation and predicts AKT inhibitor sensitivity. In contrast to phosphorylation of AKT(Thr308), the phospho-PRAS40(Thr246) epitope is highly stable in tissue samples and thus is ideal for immunohistochemistry. In summary, our study illustrates a rational approach for discovery of drug-specific biomarkers toward development of patient-tailored treatments.

Research paper thumbnail of Efficacious Intermittent Dosing of a Novel JAK2 Inhibitor in Mouse Models of Polycythemia Vera

PLoS ONE, 2012

A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor ... more A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor a Val617RPhe activating mutation in the Janus kinase 2 (JAK2) gene, and both cell culture and mouse models have established a functional role for this mutation in the development of this disease. We describe the properties of MRLB-11055, a highly potent inhibitor of both the WT and V617F forms of JAK2, that has therapeutic efficacy in erythropoietin (EPO)-driven and JAK2V617F-driven mouse models of PV. In cultured cells, MRLB-11055 blocked proliferation and induced apoptosis in a manner consistent with JAK2 pathway inhibition. MRLB-11055 effectively prevented EPO-induced STAT5 activation in the peripheral blood of acutely dosed mice, and could prevent EPO-induced splenomegaly and erythrocytosis in chronically dosed mice. In a bone marrow reconstituted JAK2V617F-luciferase murine PV model, MRLB-11055 rapidly reduced the burden of JAK2V617Fexpressing cells from both the spleen and the bone marrow. Using real-time in vivo imaging, we examined the kinetics of disease regression and resurgence, enabling the development of an intermittent dosing schedule that achieved significant reductions in both erythroid and myeloid populations with minimal impact on lymphoid cells. Our studies provide a rationale for the use of non-continuous treatment to provide optimal therapy for PV patients.

Research paper thumbnail of Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells

PLoS Biology, 2005

In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangemen... more In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B stage. A subsequent functional light chain (LC) rearrangement then results in the surface expression of IgM at the immature B cell stage. Here we show that interruption of basal IgM signaling in immature B cells, either by the inducible deletion of surface Ig via Cre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking ''back-differentiation'' of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidence of new LC gene rearrangements, suggesting an important role for basal Ig signaling in the maintenance of LC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms. Citation: Tze LE, Schram BR, Lam KP, Hogquist KA, Hippen KL, et al. (2005) Basal immunoglobulin signaling actively maintains developmental stage in immature B cells. PLoS Biol 3(3): e82.

Research paper thumbnail of Identification of sawflies and horntails (Hymenoptera, ‘Symphyta’) through DNA barcodes: successes and caveats

Molecular Ecology Resources, 2016

The 'Symphyta&amp... more The 'Symphyta' is a paraphyletic assemblage at the base of the order Hymenoptera, comprising 14 families and about 8750 species. All have phytophagous larvae, except for the Orussidae, which are parasitoids. This study presents and evaluates the results of DNA barcoding of approximately 5360 specimens of 'Symphyta', mainly adults, and 4362 sequences covering 1037 species were deemed of suitable quality for inclusion in the analysis. All extant families are represented, except for the Anaxyelidae. The majority of species and specimens are from Europe, but approximately 38% of the species and 13% of the specimens are of non-European origin. The utility of barcoding for species identification and taxonomy of 'Symphyta' is discussed on the basis of examples from each of the included families. A significant level of cryptic species diversity was apparent in many groups. Other attractive applications include the identification of immature stages without the need to rear them, community analyses based on metabarcoding of bulk samples and association of the sexes of adults.

Research paper thumbnail of I PDK1 Attenuation Fails to Prevent Tumor Formation in PTEN-Deficient Transgenic Mouse Models

Research paper thumbnail of Survival of Resting Mature B Lymphocytes Depends on BCR Signaling via the Ig¿/ß Heterodimer

Cell, 2004

We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR express... more We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR expression in mature B cells through Ig-heavy chain deletion results in apoptosis of these cells. This led to the hypothesis that survival signals from the BCR are vital for mature B cells. Here, we test two critical assumptions of this model. First, we demonstrate loss of mature B cells upon induced mutation of a signaling module of the BCR, not precluding BCR surface expression. Second, we show that the cells are also lost upon BCR inactivation in the absence of an exogenous inducer like interferon, excluding that cell death depends on previous cellular activation by the latter. Kinetic data demonstrate that BCR-less mature B cells have a severely reduced lifespan, with a half-life of 3-6 days. Together these results establish that BCR signaling is required to keep resting mature B cells alive in vivo.

Research paper thumbnail of Survival of Resting Mature B Lymphocytes Depends on BCR Signaling via the Iga/� Heterodimer

Cell, 2004

We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR express... more We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR expression in mature B cells through Ig-heavy chain deletion results in apoptosis of these cells. This led to the hypothesis that survival signals from the BCR are vital for mature B cells. Here, we test two critical assumptions of this model. First, we demonstrate loss of mature B cells upon induced mutation of a signaling module of the BCR, not precluding BCR surface expression. Second, we show that the cells are also lost upon BCR inactivation in the absence of an exogenous inducer like interferon, excluding that cell death depends on previous cellular activation by the latter. Kinetic data demonstrate that BCR-less mature B cells have a severely reduced lifespan, with a half-life of 3-6 days. Together these results establish that BCR signaling is required to keep resting mature B cells alive in vivo.

Research paper thumbnail of Interference with Immunoglobulin (Ig) Immunoreceptor Tyrosine-Based Activation Motif (Itam) Phosphorylation Modulates or Blocks B Cell Development, Depending on the Availability of an Ig Cytoplasmic Tail

J Exp Med, 2001

To determine the function of immunoglobulin (Ig) ␣ immunoreceptor tyrosine-based activation motif... more To determine the function of immunoglobulin (Ig) ␣ immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation, we generated mice in which Ig ␣ ITAM tyrosines were replaced by phenylalanines ( Ig ␣ FF/FF ). Ig ␣ FF/FF mice had a specific reduction of B1 and marginal zone B cells, whereas B2 cell development appeared to be normal, except that 1 light chain usage was increased. The mutants responded less efficiently to T cell-dependent antigens, whereas T cell-independent responses were unaffected. Upon B cell receptor ligation, the cells exhibited heightened calcium flux, weaker Lyn and Syk tyrosine phosphorylation, and phosphorylation of Ig ␣ non-ITAM tyrosines. Strikingly, when the Ig ␣ ITAM mutation was combined with a truncation of Ig ␤ , B cell development was completely blocked at the pro-B cell stage, indicating a crucial role of ITAM phosphorylation in B cell development.

Research paper thumbnail of Unterordnung Symphyta - Planzenwespen

Der Verlag und die Autoren haben alle Sorgfalt walten lassen, um vollständige und akkurate Inform... more Der Verlag und die Autoren haben alle Sorgfalt walten lassen, um vollständige und akkurate Informationen in diesem Buch zu publizieren. Der Verlag übernimmt weder Garantie noch die juristische Verantwortung oder irgendeine Haftung für die Nutzung dieser Informationen, für deren Wirtschaftlichkeit oder fehlerfreie Funktion für einen bestimmten Zweck. Der Verlag übernimmt keine Gewähr dafür, dass die beschriebenen Verfahren, Programme usw. frei von Schutzrechten Dritter sind. Der Verlag hat sich bemüht, sämtliche Rechteinhaber von Abbildungen zu ermitteln. Sollte dem Verlag gegenüber dennoch der Nachweis der Rechtsinhaberschaft geführt werden, wird das branchenübliche Honorar gezahlt. Bibliograflsche Information Der Deutschen Bibliothek Die Deutsche Bibliothek verzeichnet diese Publikation in der Deutschen Nationalbibliografie; detaillierte bibliografische Daten sind im Internet über http://dnb.ddb.de abrufbar. Alle Rechte vorbehalten 10. Auflage 2005

Research paper thumbnail of Contribution to the knowledge of sawfly fauna (Hymenoptera, Symphyta) of the Low Tatras National Park in Central Slovakia

k poznaniu fauny hrubopásych (Hymenoptera, Symphyta) Národného parku Nízke Tatry Abstrakt: Počas ... more k poznaniu fauny hrubopásych (Hymenoptera, Symphyta) Národného parku Nízke Tatry Abstrakt: Počas deviateho medzinárodného pracovného stretnutia špecialistov na hrubopáse blanokrídlovce (Hymenoptera, Symphyta) v júni 2005 bol vykonaný faunistický prieskum hrubopásych na viacerých lokalitách Národného parku Nízke Tatry. Celkovo bolo zaznamenaných 200 druhov a osem čeľadí hrubopásych. Ďalších dvanásť taxónov nebolo identifikovaných do druhu. Dolerus altivolus, D. hibernicus, Eriocampa dorpatica, Euura hastatae, Fenella monilicornis, Nematus yokohamensis tavastiensis, Pachynematus clibrichellus, Phyllocolpa excavata, P. polita, P. rolleri, Pontania gallarum, P. virilis, Pristiphora breadalbanensis, P. coactula a Tenthredo ignobilis boli zistené na Slovensku po prvýkrát. Významný počet faunisticky zaujímavých nálezov naznačuje vysokú zachovalosť študovaných prírodných stanovíšť v širšom okolí Demänovskej a Jánskej doliny, Svarína a v Národnej prírodnej rezervácii Turková.

Research paper thumbnail of Die invasive Zick-Zack-Ulmenblattwespe Aproceros leucopoda Takeuchi, 1939 (Hym., Argidae) in Deutschland

Research paper thumbnail of The nominal taxa described by K. Warncke and their types (Insecta, Hymenoptera, Apoidea)

We present a catalogue of all new taxa of bees (Insecta: Hymenoptera, Apoidea) which were describ... more We present a catalogue of all new taxa of bees (Insecta: Hymenoptera, Apoidea) which were described by Klaus Warncke. Between 1965 and 1993 he described 57 new taxa of the genus group and 887 new taxa of the species group, which are listed here with their original citation. Conformity of the type series with the original description was verified, the orthography of few taxa was corrected according to the ICZN (1985). The purpose of this paper is to summarize and to allow easy access to Warncke's work. The collection of Warncke is preserved at the Oberösterreichisches Landesmuseum in Linz (Austria), the parasitic genera are deposited in the private collection of Maximilian Schwarz (Ansfelden, Austria).

Research paper thumbnail of The Pim Kinase Inhibitor AZD1208 Enhances Apoptosis Induction By Clinically Active FLT3 Inhibitors in FLT3-ITD Acute Myeloid Leukemia Cells in Vitro and in Vivo through Synergistic Downregulation of Mcl-1 and of Bcl-xL

Research paper thumbnail of Kommentare zur Biologie, Verbreitung und Gefährdung der Pflanzenwespen Deutschlands (Hymenoptera, Symphyta)

Page 1. Kommentare zur Biologie, Verbreitung und Gefährdung der Pflanzenwespen Deutschlands (Hyme... more Page 1. Kommentare zur Biologie, Verbreitung und Gefährdung der Pflanzenwespen Deutschlands (Hymenoptera, Symphyta) Andreas TAEGER, Ewald ALTENHOFER, Stephan M. BLANK, Ewald JANSEN, Manfred KRAUS, Hubert PSCHORN-WALCHER, Carsten RITZAU ...

Research paper thumbnail of Rote Liste der Pflanzenwespen (Hymenoptera: Symphyta)

Research paper thumbnail of Symphyta. In: Dathe, H. H.; Taeger, A.; Blank, S. M. (Hrsg.): Verzeichnis der Hautflügler Deutschlands (Fauna Germanica 4)

Research paper thumbnail of Orussus smithi sp. n. and Notes on Other West Palaearctic Orussidae (Hymenoptera)

Research paper thumbnail of Unterordnung Symphyta - Pflanzenwespen

Research paper thumbnail of Rote Liste und Gesamtartenliste der Pflanzenwespen (Hymenoptera: Symphyta) Deutschlands. Stand März 2011

Liston, A.D.; Jansen, E.; Blank, S.M.; Kraus, M. & Taeger, A. (2011): Rote Liste und Gesamtartenl... more Liston, A.D.; Jansen, E.; Blank, S.M.; Kraus, M. & Taeger, A. (2011): Rote Liste und Gesamtartenliste der Pflanzenwespen (Hymenoptera: Symphyta) Deutschlands. -In: Binot-Hafke, M.; Balzer, S.; Becker, N.; Gruttke, H.; Haupt, H.; Hofbauer, N.; Ludwig, G.; Matzke-Hajek, G. & Strauch, M. (Red.): Rote Liste gefährdeter Tiere, Pflanzen und Pilze Deutschlands. Band 3: Wirbellose Tiere (Teil 1). -Münster (Landwirtschaftsverlag). -Naturschutz und Biologische Vielfalt 70 (3): 491-556. Die Rote Liste gefährdeter Tiere, Pflanzen und Pilze Deutschlands, Band 3: Wirbellose Tiere (Teil 1) (ISBN 978-3-7843-5231-2) ist zu beziehen über BfN-Schriftenvertrieb -Leserserviceim Landwirtschaftsverlag GmbH 48084 Münster

Research paper thumbnail of Hymenoptera-Hautflügler

Research paper thumbnail of Pathway-Based Identification of Biomarkers for Targeted Therapeutics: Personalized Oncology with PI3K Pathway Inhibitors

Science Translational Medicine, 2010

Although we have made great progress in understanding the complex genetic alterations that underl... more Although we have made great progress in understanding the complex genetic alterations that underlie human cancer, it has proven difficult to identify which molecularly targeted therapeutics will benefit which patients. Drug-specific modulation of oncogenic signaling pathways in specific patient subpopulations can predict responsiveness to targeted therapy. Here, we report a pathway-based phosphoprofiling approach to identify and quantify clinically relevant, drug-specific biomarkers for phosphatidylinositol 3-kinase (PI3K) pathway inhibitors that target AKT, phosphoinositide-dependent kinase 1 (PDK1), and PI3K-mammalian target of rapamycin (mTOR). We quantified 375 nonredundant PI3K pathway-relevant phosphopeptides, all containing AKT, PDK1, or mitogen-activated protein kinase substrate recognition motifs. Of these phosphopeptides, 71 were drug-regulated, 11 of them by all three inhibitors. Drug-modulated phosphoproteins were enriched for involvement in cytoskeletal reorganization (filamin, stathmin, dynamin, PAK4, and PTPN14), vesicle transport (LARP1, VPS13D, and SLC20A1), and protein translation (S6RP and PRAS40). We then generated phosphospecific antibodies against selected, drug-regulated phosphorylation sites that would be suitable as biomarker tools for PI3K pathway inhibitors. As proof of concept, we show clinical translation feasibility for an antibody against phospho-PRAS40(Thr246). Evaluation of binding of this antibody in human cancer cell lines, a PTEN (phosphatase and tensin homolog deleted from chromosome 10)-deficient mouse prostate tumor model, and triple-negative breast tumor tissues showed that phospho-PRAS40(Thr246) positively correlates with PI3K pathway activation and predicts AKT inhibitor sensitivity. In contrast to phosphorylation of AKT(Thr308), the phospho-PRAS40(Thr246) epitope is highly stable in tissue samples and thus is ideal for immunohistochemistry. In summary, our study illustrates a rational approach for discovery of drug-specific biomarkers toward development of patient-tailored treatments.

Research paper thumbnail of Efficacious Intermittent Dosing of a Novel JAK2 Inhibitor in Mouse Models of Polycythemia Vera

PLoS ONE, 2012

A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor ... more A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor a Val617RPhe activating mutation in the Janus kinase 2 (JAK2) gene, and both cell culture and mouse models have established a functional role for this mutation in the development of this disease. We describe the properties of MRLB-11055, a highly potent inhibitor of both the WT and V617F forms of JAK2, that has therapeutic efficacy in erythropoietin (EPO)-driven and JAK2V617F-driven mouse models of PV. In cultured cells, MRLB-11055 blocked proliferation and induced apoptosis in a manner consistent with JAK2 pathway inhibition. MRLB-11055 effectively prevented EPO-induced STAT5 activation in the peripheral blood of acutely dosed mice, and could prevent EPO-induced splenomegaly and erythrocytosis in chronically dosed mice. In a bone marrow reconstituted JAK2V617F-luciferase murine PV model, MRLB-11055 rapidly reduced the burden of JAK2V617Fexpressing cells from both the spleen and the bone marrow. Using real-time in vivo imaging, we examined the kinetics of disease regression and resurgence, enabling the development of an intermittent dosing schedule that achieved significant reductions in both erythroid and myeloid populations with minimal impact on lymphoid cells. Our studies provide a rationale for the use of non-continuous treatment to provide optimal therapy for PV patients.

Research paper thumbnail of Basal Immunoglobulin Signaling Actively Maintains Developmental Stage in Immature B Cells

PLoS Biology, 2005

In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangemen... more In developing B lymphocytes, a successful V(D)J heavy chain (HC) immunoglobulin (Ig) rearrangement establishes HC allelic exclusion and signals pro-B cells to advance in development to the pre-B stage. A subsequent functional light chain (LC) rearrangement then results in the surface expression of IgM at the immature B cell stage. Here we show that interruption of basal IgM signaling in immature B cells, either by the inducible deletion of surface Ig via Cre-mediated excision or by incubating cells with the tyrosine kinase inhibitor herbimycin A or the phosphatidylinositol 3-kinase inhibitor wortmannin, led to a striking ''back-differentiation'' of cells to an earlier stage in B cell development, characterized by the expression of pro-B cell genes. Cells undergoing this reversal in development also showed evidence of new LC gene rearrangements, suggesting an important role for basal Ig signaling in the maintenance of LC allelic exclusion. These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms. Citation: Tze LE, Schram BR, Lam KP, Hogquist KA, Hippen KL, et al. (2005) Basal immunoglobulin signaling actively maintains developmental stage in immature B cells. PLoS Biol 3(3): e82.