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https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#1
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28586167/card9-dependent-il-1%C3%AE-regulates-il-22-production-from-group-3-innate-lymphoid-cells-and-promotes-colitis-associated-cancer
#2
Hanna Bergmann, Susanne Roth, Konstanze Pechloff, Elina A Kiss, Sabine Kuhn, Mathias Heikenwälder, Andreas Diefenbach, Florian R Greten, Jürgen Ruland
Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28578388/antibody-blockade-of-clec12a-delays-eae-onset-and-attenuates-disease-severity-by-impairing-myeloid-cell-cns-infiltration-and-restoring-positive-immunity
#3
Divya Sagar, Narendra P Singh, Rashida Ginwala, Xiaofang Huang, Ramila Philip, Mitzi Nagarkatti, Prakash Nagarkatti, Konstantin Neumann, Jürgen Ruland, Allison M Andrews, Servio H Ramirez, Zafar K Khan, Pooja Jain
The mechanism of dendritic cells (DCs) recruitment across the blood brain barrier (BBB) during neuroinflammation has been the least explored amongst all leukocytes. For cells of myeloid origin, while integrins function at the level of adhesion, the importance of lectins remains unknown. Here, we identified functions of one C-type lectin receptor, CLEC12A, in facilitating DC binding and transmigration across the BBB in response to CCL2 chemotaxis. To test function of CLEC12A in an animal model of multiple sclerosis (MS), we administered blocking antibody to CLEC12A that significantly ameliorated disease scores in MOG35-55-induced progressive, as well as PLP138-151-induced relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533239/plasmodium-falciparum-and-p-vivax-demonstrate-contrasting-chloroquine-resistance-reversal-phenotypes
#4
Grennady Wirjanata, Irene Handayuni, Pak Prayoga, Leo Leonardo, Dwi Apriyanti, Leily Trianty, Ruland Wandosa, Basbak Gobay, Enny Kenangalem, Jeanne Rini Poespoprodjo, Rintis Noviyanti, Dennis E Kyle, Qin Cheng, Ric N Price, Jutta Marfurt
High-grade chloroquine (CQ) resistance has emerged in both P. falciparum and P. vivax The aim of the present study was to investigate phenotypic differences of CQ resistance in both of these species and the ability of known CQ resistance reversal agents (CQRRAs) to alter CQ susceptibility.Between April 2015 and April 2016, the potential of verapamil (VP), mibefradil (MF), L703,606 (L7), and primaquine (PQ) to reverse CQ resistance was assessed in 46 P. falciparum and 34 P. vivax clinical isolates in Papua, Indonesia, where CQ resistance is present in both species, using a modified schizont maturation assay...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28465277/shifting-practices-toward-recovery-oriented-care-through-an-e-recovery-portal-in-community-mental-health-care-a-mixed-methods-exploratory-study
#5
Deede Gammon, Monica Strand, Lillian Sofie Eng, Elin Børøsund, Cecilie Varsi, Cornelia Ruland
BACKGROUND: Mental health care is shifting from a primary focus on symptom reduction toward personal recovery-oriented care, especially for persons with long-term mental health care needs. Web-based portals may facilitate this shift, but little is known about how such tools are used or the role they may play in personal recovery. OBJECTIVE: The aim was to illustrate uses and experiences with the secure e-recovery portal "ReConnect" as an adjunct to ongoing community mental health care and explore its potential role in shifting practices toward recovery...
May 2, 2017: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/28457793/multi-site-neurogenin3-phosphorylation-controls-pancreatic-endocrine-differentiation
#6
Roberta Azzarelli, Christopher Hurley, Magdalena K Sznurkowska, Steffen Rulands, Laura Hardwick, Ivonne Gamper, Fahad Ali, Laura McCracken, Christopher Hindley, Fiona McDuff, Sonia Nestorowa, Richard Kemp, Kenneth Jones, Berthold Göttgens, Meritxell Huch, Gerard Evan, Benjamin D Simons, Douglas Winton, Anna Philpott
The proneural transcription factor Neurogenin3 (Ngn3) plays a critical role in pancreatic endocrine cell differentiation, although regulation of Ngn3 protein is largely unexplored. Here we demonstrate that Ngn3 protein undergoes cyclin-dependent kinase (Cdk)-mediated phosphorylation on multiple serine-proline sites. Replacing wild-type protein with a phosphomutant form of Ngn3 increases α cell generation, the earliest endocrine cell type to be formed in the developing pancreas. Moreover, un(der)phosphorylated Ngn3 maintains insulin expression in adult β cells in the presence of elevated c-Myc and enhances endocrine specification during ductal reprogramming...
May 8, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28426539/the-effect-of-cancer-patients-and-their-family-caregivers-physical-and-emotional-symptoms-on-caregiver-burden
#7
Safora Johansen, Milada Cvancarova, Cornelia Ruland
BACKGROUND: Although there is significant evidence that the family caregivers (FCs) of cancer patients can experience significant caregiver burden and symptoms, less is known about the relationships between FCs and patient characteristics that influence caregiver burden. OBJECTIVE: The purpose of this study was to examine the effect of cancer patients' and FCs' symptoms and demographic characteristics on caregiver burden at initiation of the patients' radiation treatment...
April 20, 2017: Cancer Nursing
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#8
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28388907/transitions-from-biomedical-to-recovery-oriented-practices-in-mental-health-a-scoping-review-to-explore-the-role-of-internet-based-interventions
#9
Monica Strand, Deede Gammon, Cornelia M Ruland
BACKGROUND: The Internet is transforming mental health care services by increasing access to, and potentially improving the quality of, care. Internet-based interventions in mental health can potentially play a role in transitions from biomedical to recovery-oriented research and practices, but an overview of what this may entail, current work, and issues that need addressing, is lacking. The objective of this study is to describe Internet-based recovery-oriented interventions (referred to as e-recovery) and current research, and to identify gaps and issues relevant to advancing recovery research and practices through opportunities provided by the Internet...
April 7, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28369101/risk-factors-for-gastroenteritis-associated-with-canal-swimming-in-two-cities-in-the-netherlands-during-the-summer-of-2015-a-prospective-study
#10
Rosa Joosten, Gerard Sonder, Saara Parkkali, Diederik Brandwagt, Ewout Fanoy, Lapo Mughini-Gras, Willemijn Lodder, Erik Ruland, Evelien Siedenburg, Suzanne Kliffen, Wilfrid van Pelt
Urban canal swimming events are popular in the Netherlands. In 2015, two city canal swimming events took place, in Utrecht (Utrecht Singel Swim, USS) and in Amsterdam (Amsterdam City Swim, ACS). This prospective study characterizes the health risks associated with swimming in urban waters. Online questionnaires were sent to 160 (USS) and 2,692 (ACS) participants, with relatives of participants who did not swim completing the questionnaire as a control. Swimming water specimens and stool specimens of diarrheic participants in the ACS group were analysed...
2017: PloS One
https://www.readbyqxmd.com/read/28295265/card9-controls-dectin-1-induced-t-cell-cytotoxicity-and-tumor-growth-in-mice
#11
Tobias Haas, Simon Heidegger, Alexander Wintges, Michael Bscheider, Sarah Bek, Julius C Fischer, Gabriel Eisenkolb, Martina Schmickl, Silvia Spoerl, Christian Peschel, Hendrik Poeck, Jürgen Ruland
Activation of the C-type lectin receptor Dectin-1 by β-glucans triggers multiple signals within DCs that result in activation of innate immunity. While these mechanisms can potently prime CD8(+) cytotoxic T-cell (CTL) responses without additional adjuvants, the Dectin-1 effector pathways that control CTL induction remain unclear. Here we demonstrate that Dectin-1-induced CTL cross-priming in mice does not require inflammasome activation but strictly depends on the adapter protein Card9 in vitro. In vivo, Dectin-1-mediated Card9 activation after vaccination drives both expansion and activation of Ag-specific CTLs, resulting in long-lasting CTL responses that are sufficient to protect mice from tumor challenge...
May 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28249643/chromosome-instability-in-tumor-resection-margins-of-primary-oscc-is-a-predictor-of-local-recurrence
#12
Damiana D C G Pierssens, Maarten C Borgemeester, Stijn J H van der Heijden, Carine J Peutz-Kootstra, Andrea M Ruland, Annick M Haesevoets, Peter A W H Kessler, Bernd Kremer, Ernst-Jan M Speel
BACKGROUND: The local recurrence rate in oral squamous cell cancer (OSCC) hardly decreases. This is partly due to the presence of (pre)malignant cells in the remaining tissue after resection, that may lead to the development of a new tumor in time. Detection of histologically (pre)malignant cells in the tumor resection margins should predict these patients at risk for recurrence, however this appears to be difficult in routine practice. Purpose of this study was to apply easy-to-use molecular tests for more accurate detection of (pre)malignant cells in histopathologically tumor-free margins, to improve diagnosis of patients at risk...
March 2017: Oral Oncology
https://www.readbyqxmd.com/read/28248284/defining-stem-cell-dynamics-and-migration-during-wound-healing-in-mouse-skin-epidermis
#13
Mariaceleste Aragona, Sophie Dekoninck, Steffen Rulands, Sandrine Lenglez, Guilhem Mascré, Benjamin D Simons, Cédric Blanpain
Wound healing is essential to repair the skin after injury. In the epidermis, distinct stem cells (SCs) populations contribute to wound healing. However, how SCs balance proliferation, differentiation and migration to repair a wound remains poorly understood. Here, we show the cellular and molecular mechanisms that regulate wound healing in mouse tail epidermis. Using a combination of proliferation kinetics experiments and molecular profiling, we identify the gene signatures associated with proliferation, differentiation and migration in different regions surrounding the wound...
March 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28109561/lithium-reverses-behavioral-and-axonal-transport-related-changes-associated-with-ank3-bipolar-disorder-gene-disruption
#14
Michael G Gottschalk, Melanie P Leussis, Tillmann Ruland, Klaudio Gjeluci, Tracey L Petryshen, Sabine Bahn
Ankyrin 3 (ANK3) has been implicated as a genetic risk factor for bipolar disorder (BD), however the resulting pathophysiological and treatment implications remain elusive. In a preclinical systems biological approach, we aimed to characterize the behavioral and proteomic effects of Ank3 haploinsufficiency and chronic mood-stabilizer treatment in mice. Psychiatric-related behavior was evaluated with the novelty-suppressed feeding (NSF) paradigm, elevated plus maze (EPM) and a passive avoidance task (PAT). Tandem mass spectrometry (MS(E)) was employed for hippocampal proteome profiling...
January 18, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27941931/in-vivo-functional-dissection-of-a-context-dependent-role-for-hif1%C3%AE-in-pancreatic-tumorigenesis
#15
T Cheng, Z Jian, K Li, S Raulefs, I Regel, S Shen, X Zou, J Ruland, G O Ceyhan, H Friess, C W Michalski, J Kleeff, B Kong
Hypoxia-inducible factor 1α (Hif1α) is a key regulator of cellular adaptation and survival under hypoxic conditions. In pancreatic ductal adenocarcinoma (PDAC), it has been recently shown that genetic ablation of Hif1α accelerates tumour development by promoting tumour-supportive inflammation in mice, questioning its role as the key downstream target of many oncogenic signals of PDAC. Likely, Hif1α has a context-dependent role in pancreatic tumorigenesis. To further analyse this, murine PDAC cell lines with reduced Hif1α expression were generated using shRNA transfection...
December 12, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27926862/vav-proteins-are-key-regulators-of-card9-signaling-for-innate-antifungal-immunity
#16
Susanne Roth, Hanna Bergmann, Martin Jaeger, Assa Yeroslaviz, Konstantin Neumann, Paul-Albert Koenig, Clarissa Prazeres da Costa, Lesley Vanes, Vinod Kumar, Melissa Johnson, Mauricio Menacho-Márquez, Bianca Habermann, Victor L Tybulewicz, Mihai Netea, Xosé R Bustelo, Jürgen Ruland
Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adaptor Card9. Although Card9 is essential for antifungal defense, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-κB control and proinflammatory gene transcription...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27851915/epigenomic-profiling-of-human-cd4-t-cells-supports-a-linear-differentiation-model-and-highlights-molecular-regulators-of-memory-development
#17
Pawel Durek, Karl Nordström, Gilles Gasparoni, Abdulrahman Salhab, Christopher Kressler, Melanie de Almeida, Kevin Bassler, Thomas Ulas, Florian Schmidt, Jieyi Xiong, Petar Glažar, Filippos Klironomos, Anupam Sinha, Sarah Kinkley, Xinyi Yang, Laura Arrigoni, Azim Dehghani Amirabad, Fatemeh Behjati Ardakani, Lars Feuerbach, Oliver Gorka, Peter Ebert, Fabian Müller, Na Li, Stefan Frischbutter, Stephan Schlickeiser, Carla Cendon, Sebastian Fröhler, Bärbel Felder, Nina Gasparoni, Charles D Imbusch, Barbara Hutter, Gideon Zipprich, Yvonne Tauchmann, Simon Reinke, Georgi Wassilew, Ute Hoffmann, Andreas S Richter, Lina Sieverling, Hyun-Dong Chang, Uta Syrbe, Ulrich Kalus, Jürgen Eils, Benedikt Brors, Thomas Manke, Jürgen Ruland, Thomas Lengauer, Nikolaus Rajewsky, Wei Chen, Jun Dong, Birgit Sawitzki, Ho-Ryun Chung, Philip Rosenstiel, Marcel H Schulz, Joachim L Schultze, Andreas Radbruch, Jörn Walter, Alf Hamann, Julia K Polansky
The impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA(+) CD4(+) Tmem cells from blood and CD69(+) Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27716515/mutations-in-the-histone-modifier-prdm6-are-associated-with-isolated-nonsyndromic-patent-ductus-arteriosus
#18
Na Li, Lakshman Subrahmanyan, Emily Smith, Xiaoqing Yu, Samir Zaidi, Murim Choi, Shrikant Mane, Carol Nelson-Williams, Mohaddeseh Behjati, Mohammad Kazemi, Mohammad Hashemi, Mohsen Fathzadeh, Anand Narayanan, Likun Tian, Farhad Montazeri, Mitra Mani, Michael L Begleiter, Brian G Coon, Henry T Lynch, Eric N Olson, Hongyu Zhao, Jürgen Ruland, Richard P Lifton, Arya Mani
No abstract text is available yet for this article.
October 6, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27692612/k-efflux-independent-nlrp3-inflammasome-activation-by-small-molecules-targeting-mitochondria
#19
Christina J Groß, Ritu Mishra, Katharina S Schneider, Guillaume Médard, Jennifer Wettmarshausen, Daniela C Dittlein, Hexin Shi, Oliver Gorka, Paul-Albert Koenig, Stephan Fromm, Giovanni Magnani, Tamara Ćiković, Lara Hartjes, Joachim Smollich, Avril A B Robertson, Matthew A Cooper, Marc Schmidt-Supprian, Michael Schuster, Kate Schroder, Petr Broz, Claudia Traidl-Hoffmann, Bruce Beutler, Bernhard Kuster, Jürgen Ruland, Sabine Schneider, Fabiana Perocchi, Olaf Groß
Imiquimod is a small-molecule ligand of Toll-like receptor-7 (TLR7) that is licensed for the treatment of viral infections and cancers of the skin. Imiquimod has TLR7-independent activities that are mechanistically unexplained, including NLRP3 inflammasome activation in myeloid cells and apoptosis induction in cancer cells. We investigated the mechanism of inflammasome activation by imiquimod and the related molecule CL097 and determined that K(+) efflux was dispensable for NLRP3 activation by these compounds...
October 18, 2016: Immunity
https://www.readbyqxmd.com/read/27646934/dynamic-landscape-of-pancreatic-carcinogenesis-reveals-early-molecular-networks-of-malignancy
#20
Bo Kong, Philipp Bruns, Nora A Behler, Ligong Chang, Anna Melissa Schlitter, Jing Cao, Andreas Gewies, Jürgen Ruland, Sina Fritzsche, Nataliya Valkovskaya, Ziying Jian, Ivonne Regel, Susanne Raulefs, Martin Irmler, Johannes Beckers, Helmut Friess, Mert Erkan, Nikola S Mueller, Susanne Roth, Thilo Hackert, Irene Esposito, Fabian J Theis, Jörg Kleeff, Christoph W Michalski
OBJECTIVE: The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. DESIGN: We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated Kras(G12D)-driven pancreatic ductal adenocarcinoma...
September 19, 2016: Gut
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