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Schwinn cells

Martin Chopra, Marlene Biehl, Tim Steinfatt, Andreas Brandl, Juliane Kums, Jorge Amich, Martin Vaeth, Janina Kuen, Rafaela Holtappels, Jürgen Podlech, Anja Mottok, Sabrina Kraus, Ana-Laura Jordán-Garrote, Carina A Bäuerlein, Christian Brede, Eliana Ribechini, Andrea Fick, Axel Seher, Johannes Polz, Katja J Ottmüller, Jeanette Baker, Hidekazu Nishikii, Miriam Ritz, Katharina Mattenheimer, Stefanie Schwinn, Thorsten Winter, Viktoria Schäfer, Sven Krappmann, Hermann Einsele, Thomas D Müller, Matthias J Reddehase, Manfred B Lutz, Daniela N Männel, Friederike Berberich-Siebelt, Harald Wajant, Andreas Beilhack
Donor CD4(+)Foxp3(+) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT [allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology...
August 22, 2016: Journal of Experimental Medicine
Rachel Friedman Ohana, Sergiy Levin, Monika G Wood, Kris Zimmerman, Melanie L Dart, Marie K Schwinn, Thomas A Kirkland, Robin Hurst, H Tetsuo Uyeda, Lance P Encell, Keith V Wood
The benefits provided by phenotypic screening of compound libraries are often countered by difficulties in identifying the underlying cellular targets. We recently described a new approach utilizing a chloroalkane capture tag, which can be chemically attached to bioactive compounds to facilitate the isolation of their respective targets for subsequent identification by mass spectrometry. The tag minimally affects compound potency and membrane permeability, enabling target engagement inside cells. Effective enrichment of these targets is achieved through selectivity in both their rapid capture onto immobilized HaloTag and their subsequent release by competitive elution...
September 16, 2016: ACS Chemical Biology
Monica Jordheim, Kate Calcott, Kevin S Gould, Kevin M Davies, Kathy E Schwinn, Øyvind M Andersen
Vegetative shoots of a naturalized population of purple-leaved plectranthus (Plectranthus ciliatus, Lamiaceae) were found to contain four main anthocyanins: peonidin 3-(6″-caffeoyl-β-glucopyranoside)-5-β-glucopyranoside, peonidin 3-(6″-caffeoyl-β-glucopyranoside)-5-(6‴-malonyl-β-glucopyranoside), peonidin 3-(6″-E-p-coumaroyl-β-glucopyranoside)-5-(6‴-malonyl-β-glucopyranoside), and peonidin 3-(6″-E-p-coumaroyl-β-glucopyranoside)-5-β-glucopyranoside. The first three of these pigments have not been reported previously from any plant...
August 2016: Phytochemistry
J J Gross, A-C Schwinn, F Schmitz-Hsu, F Menzi, C Drögemüller, C Albrecht, R M Bruckmaier
During the last months, the number of reports on Holstein calves suffering from incurable idiopathic diarrhea dramatically increased. Affected calves showed severe hypocholesterolemia and mostly died within days up to a few months after birth. This new autosomal monogenic recessive inherited fat metabolism disorder, termed cholesterol deficiency (CD), is caused by a loss of function mutation of the bovine gene. The objective of the present study was to investigate specific components of lipid metabolism in 6 homozygous for the mutation (CDS) and 6 normal Holstein calves with different genotypes...
April 2016: Journal of Animal Science
Sebastian Dietl, Stefanie Schwinn, Susanne Dietl, Simone Riedel, Frank Deinlein, Stefan Rutkowski, Andre O von Bueren, Jürgen Krauss, Tilmann Schweitzer, Giles H Vince, Daniel Picard, Matthias Eyrich, Andreas Rosenwald, Vijay Ramaswamy, Michael D Taylor, Marc Remke, Camelia M Monoranu, Andreas Beilhack, Paul G Schlegel, Matthias Wölfl
BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup. METHODS: We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma. RESULTS: Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture...
2016: BMC Cancer
Irina Gradinaru, Ekaterina Babaeva, Debra A Schwinn, Anush Oganesian
α1a Adrenergic receptors (α1aARs) are the predominant AR subtype in human vascular smooth muscle cells (SMCs). α1aARs in resistance vessels are crucial in the control of blood pressure, yet the impact of naturally occurring human α1aAR genetic variants in cardiovascular disorders remains poorly understood. To this end, we present novel findings demonstrating that 3D cultures of vascular SMCs expressing human α1aAR-247R (247R) genetic variant demonstrate significantly increased SMC contractility compared with cells expressing the α1aAR-WT (WT) receptor...
2015: PloS One
Andrew S Dixon, Marie K Schwinn, Mary P Hall, Kris Zimmerman, Paul Otto, Thomas H Lubben, Braeden L Butler, Brock F Binkowski, Thomas Machleidt, Thomas A Kirkland, Monika G Wood, Christopher T Eggers, Lance P Encell, Keith V Wood
Protein-fragment complementation assays (PCAs) are widely used for investigating protein interactions. However, the fragments used are structurally compromised and have not been optimized nor thoroughly characterized for accurately assessing these interactions. We took advantage of the small size and bright luminescence of NanoLuc to engineer a new complementation reporter (NanoBiT). By design, the NanoBiT subunits (i.e., 1.3 kDa peptide, 18 kDa polypeptide) weakly associate so that their assembly into a luminescent complex is dictated by the interaction characteristics of the target proteins onto which they are appended...
February 19, 2016: ACS Chemical Biology
M Schulze, O Fedorchenko, T G Zink, C B Knobbe-Thomsen, S Kraus, S Schwinn, A Beilhack, G Reifenberger, C M Monoranu, A-L Sirén, E Jeanclos, A Gohla
Glioblastoma is the most aggressive primary brain tumor in adults. Although the rapid recurrence of glioblastomas after treatment is a major clinical challenge, the relationships between tumor growth and intracerebral spread remain poorly understood. We have identified the cofilin phosphatase chronophin (gene name: pyridoxal phosphatase, PDXP) as a glial tumor modifier. Monoallelic PDXP loss was frequent in four independent human astrocytic tumor cohorts and increased with tumor grade. We found that aberrant PDXP promoter methylation can be a mechanism leading to further chronophin downregulation in glioblastomas, which correlated with shorter glioblastoma patient survival...
June 16, 2016: Oncogene
Martin Chopra, Andreas Brandl, Daniela Siegmund, Anja Mottok, Viktoria Schäfer, Marlene Biehl, Sabrina Kraus, Carina A Bäuerlein, Miriam Ritz, Katharina Mattenheimer, Stefanie Schwinn, Axel Seher, Thomas Grabinger, Hermann Einsele, Andreas Rosenwald, Thomas Brunner, Andreas Beilhack, Harald Wajant
Inhibition of the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) system reduces intestinal cell death and disease development in several models of colitis. In view of the crucial role of TNF and intestinal cell death in graft-versus-host disease (GVHD) and the ability of TWEAK to enhance TNF-induced cell death, we tested here the therapeutic potential of Fn14 blockade on allogeneic hematopoietic cell transplantation (allo-HCT)-induced intestinal GVHD...
July 23, 2015: Blood
Thomas Machleidt, Carolyn C Woodroofe, Marie K Schwinn, Jacqui Méndez, Matthew B Robers, Kris Zimmerman, Paul Otto, Danette L Daniels, Thomas A Kirkland, Keith V Wood
Dynamic interactions between proteins comprise a key mechanism for temporal control of cellular function and thus hold promise for development of novel drug therapies. It remains technically challenging, however, to quantitatively characterize these interactions within the biologically relevant context of living cells. Although, bioluminescence resonance energy transfer (BRET) has often been used for this purpose, its general applicability has been hindered by limited sensitivity and dynamic range. We have addressed this by combining an extremely bright luciferase (Nanoluc) with a means for tagging intracellular proteins with a long-wavelength fluorophore (HaloTag)...
August 21, 2015: ACS Chemical Biology
Sarah R Slauson, Donna M Peters, Marie K Schwinn, Paul L Kaufman, B'Ann T Gabelt, Curtis R Brandt
PURPOSE: Purified Clostridium botulinum exoenzyme C3 transferase (C3) effects on the actin cytoskeleton in human trabecular meshwork cells (HTM) and on the outflow facility response in monkey organ-cultured anterior segments (MOCAS) were determined in the presence or absence of viral vectors. METHODS: Human adenovirus type 5 (AdV) and feline immunodeficiency virus (FIV) vectors were produced using kits. Cell soluble purified C3 (C3cs) was purchased commercially...
April 2015: Investigative Ophthalmology & Visual Science
P Anoop Chandran, Andreas Keller, Lasse Weinmann, Ahmed Adel Seida, Matthias Braun, Katerina Andreev, Birgitt Fischer, Evi Horn, Stefanie Schwinn, Markus Junker, Roland Houben, Yvonne Dombrowski, Johannes Dietl, Susetta Finotto, Matthias Wölfl, Gunter Meister, Jörg Wischhusen
Cytokine secretion and degranulation represent key components of CD8(+) T-cell cytotoxicity. While transcriptional blockade of IFN-γ and inhibition of degranulation by TGF-β are well established, we wondered whether TGF-β could also induce immune-regulatory miRNAs in human CD8(+) T cells. We used miRNA microarrays and high-throughput sequencing in combination with qRT-PCR and found that TGF-β promotes expression of the miR-23a cluster in human CD8(+) T cells. Likewise, TGF-β up-regulated expression of the cluster in CD8(+) T cells from wild-type mice, but not in cells from mice with tissue-specific expression of a dominant-negative TGF-β type II receptor...
October 2014: Journal of Leukocyte Biology
Maren Kleine-Brueggeney, Irina Gradinaru, Ekaterina Babaeva, Debra A Schwinn, Anush Oganesian
The role of naturally occurring human α1a-Adrenergic Receptor (α1aAR) genetic variants associated with cardiovascular disorders is poorly understood. Here, we present the novel findings that expression of human α1aAR-247R (247R) genetic variant in cardiomyoblasts leads to transition of cardiomyoblasts into a fibroblast-like phenotype, evidenced by morphology and distinct de novo expression of characteristic genes. These fibroblast-like cells exhibit constitutive, high proliferative capacity and agonist-induced hypertrophy compared with cells prior to transition...
September 2014: Cellular Signalling
Martin Chopra, Sabrina Kraus, Stefanie Schwinn, Miriam Ritz, Katharina Mattenheimer, Anja Mottok, Andreas Rosenwald, Hermann Einsele, Andreas Beilhack
To promote cancer research and to develop innovative therapies, refined pre-clinical mouse tumor models that mimic the actual disease in humans are of dire need. A number of neoplasms along the B cell lineage are commonly initiated by a translocation recombining c-myc with the immunoglobulin heavy-chain gene locus. The translocation is modeled in the C.129S1-Igha(tm1(Myc)Janz)/J mouse which has been previously engineered to express c-myc under the control of the endogenous IgH promoter. This transgenic mouse exhibits B cell hyperplasia and develops diverse B cell tumors...
2013: PloS One
Martin Chopra, Isabell Lang, Steffen Salzmann, Christina Pachel, Sabrina Kraus, Carina A Bäuerlein, Christian Brede, Ana-Laura Jordán Garrote, Katharina Mattenheimer, Miriam Ritz, Stefanie Schwinn, Carolin Graf, Viktoria Schäfer, Stefan Frantz, Hermann Einsele, Harald Wajant, Andreas Beilhack
Multiple activities are ascribed to the cytokine tumor necrosis factor (TNF) in health and disease. In particular, TNF was shown to affect carcinogenesis in multiple ways. This cytokine acts via the activation of two cell surface receptors, TNFR1, which is associated with inflammation, and TNFR2, which was shown to cause anti-inflammatory signaling. We assessed the effects of TNF and its two receptors on the progression of pancreatic cancer by in vivo bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02 cells...
2013: PloS One
Beilei Lei, Debra A Schwinn, Daniel P Morris
Stimulation of α1aAdrenergic Receptors (ARs) is known to have anti-proliferative and hypertrophic effects; however, some studies also suggests this receptor can increase cell proliferation. Surprisingly, we find the α1aAR expressed in rat-1 fibroblasts can produce either phenotype, depending exclusively on agonist concentration. Stimulation of the α1aAR by high dose phenylephrine (>10(-7) M) induces an antiproliferative, hypertrophic response accompanied by robust and extended p38 activation. Inhibition of p38 with SB203580 prevented the antiproliferative response, while inhibition of Erk or Jnk had no effect...
2013: PloS One
Matthias Wölfl, Stefanie Schwinn, Young-Eun Yoo, Marie L Reß, Matthias Braun, Martin Chopra, Susanne C Schreiber, Victor I Ayala, Claes Ohlen, Matthias Eyrich, Andreas Beilhack, Paul G Schlegel
Src-kinase inhibitors hold great potential as targeted therapy against malignant cells. However, such inhibitors may also affect nonmalignant cells and cause pronounced off-target effects. We investigated the role of the dual kinase inhibitor dasatinib on human myeloid cells. Dasatinib is clinically used for the treatment of bcr/abl⁺ leukemias because it blocks the mutated tyrosine kinase abl. To understand its effect on the development of antigen-specific T-cell responses, we assessed antigen-specific priming of human, naïve T cells...
August 15, 2013: Blood
Matthew D Galbraith, Mary A Allen, Claire L Bensard, Xiaoxing Wang, Marie K Schwinn, Bo Qin, Henry W Long, Danette L Daniels, William C Hahn, Robin D Dowell, Joaquín M Espinosa
The transcription factor HIF1A is a key mediator of the cellular response to hypoxia. Despite the importance of HIF1A in homeostasis and various pathologies, little is known about how it regulates RNA polymerase II (RNAPII). We report here that HIF1A employs a specific variant of the Mediator complex to stimulate RNAPII elongation. The Mediator-associated kinase CDK8, but not the paralog CDK19, is required for induction of many HIF1A target genes. HIF1A induces binding of CDK8-Mediator and the super elongation complex (SEC), containing AFF4 and CDK9, to alleviate RNAPII pausing...
June 6, 2013: Cell
Rachel Deplus, Benjamin Delatte, Marie K Schwinn, Matthieu Defrance, Jacqui Méndez, Nancy Murphy, Mark A Dawson, Michael Volkmar, Pascale Putmans, Emilie Calonne, Alan H Shih, Ross L Levine, Olivier Bernard, Thomas Mercher, Eric Solary, Marjeta Urh, Danette L Daniels, François Fuks
TET proteins convert 5-methylcytosine to 5-hydroxymethylcytosine, an emerging dynamic epigenetic state of DNA that can influence transcription. Evidence has linked TET1 function to epigenetic repression complexes, yet mechanistic information, especially for the TET2 and TET3 proteins, remains limited. Here, we show a direct interaction of TET2 and TET3 with O-GlcNAc transferase (OGT). OGT does not appear to influence hmC activity, rather TET2 and TET3 promote OGT activity. TET2/3-OGT co-localize on chromatin at active promoters enriched for H3K4me3 and reduction of either TET2/3 or OGT activity results in a direct decrease in H3K4me3 and concomitant decreased transcription...
March 6, 2013: EMBO Journal
Kevin M Davies, Simon C Deroles, Murray R Boase, Don A Hunter, Kathy E Schwinn
RNA interference (RNAi) is one of the most commonly used techniques for examining the function of genes of interest. In this chapter we present two examples of RNAi that use the particle inflow gun for delivery of the DNA constructs. In one example transient RNAi is used to show the function of an anthocyanin regulatory gene in flower petals. In the second example stably transformed cell cultures are produced with an RNAi construct that results in a change in the anthocyanin hydroxylation pattern.
2013: Methods in Molecular Biology
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