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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
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...
September 24, 2016: Immunity
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
Jelena Mirkovic, Olöf Birna Kristjansdottir, Una Stenberg, Tonje Krogseth, Kurt C Stange, Cornelia M Ruland
BACKGROUND: An increasing number of research studies in the psychological and biobehavioral sciences support incorporating patients' personal strengths into illness management as a way to empower and activate the patients, thus improving their health and well-being. However, lack of attention to patients' personal strengths is still reported in patient-provider communication. Information technology (IT) has great potential to support strengths-based patient-provider communication and collaboration, but knowledge about the users' requirements and preferences is inadequate...
2016: JMIR Research Protocols
Maria Jose Bruzzone, Rick Gill, Sean Ruland
No abstract text is available yet for this article.
August 23, 2016: Neurology
Steffen Rulands, Benjamin D Simons
The coordination of cell proliferation and differentiation is central to the development and maintenance of tissues, while its dysregulation underlies the transition to diseased states. By combining lineage tracing with transcriptional profiling and marker-based assays, statistical methods are delivering insights into the dynamics of stem cells and their developmental precursors. These studies have provided evidence for molecular heterogeneity and fate priming, and have revealed a role for stochasticity in stem cell fate, refocusing the search for regulatory mechanisms...
July 27, 2016: Current Opinion in Cell Biology
Judith Alferink, Sabine Specht, Hannah Arends, Beatrix Schumak, Kim Schmidt, Christina Ruland, Ramona Lundt, Andrea Kemter, Andrea Dlugos, Janina M Kuepper, Karola Poppensieker, Matthias Findeiss, Önder Albayram, David-M Otte, Janine Marazzi, Jürg Gertsch, Irmgard Förster, Wolfgang Maier, Stefanie Scheu, Achim Hoerauf, Andreas Zimmer
Cerebral malaria is a severe and often fatal complication of Plasmodium falciparum infection. It is characterized by parasite sequestration, a breakdown of the blood-brain barrier, and a strong inflammation in the brain. We investigated the role of the cannabinoid receptor 2 (CB2), an important modulator of neuroinflammatory responses, in experimental cerebral malaria (ECM). Strikingly, mice with a deletion of the CB2-encoding gene (Cnr2(-/-)) inoculated with Plasmodium berghei ANKA erythrocytes exhibited enhanced survival and a diminished blood-brain barrier disruption...
September 9, 2016: Journal of Biological Chemistry
Ulrike Höckendorf, Monica Yabal, Tobias Herold, Enkhtsetseg Munkhbaatar, Stephanie Rott, Stefanie Jilg, Johanna Kauschinger, Giovanni Magnani, Florian Reisinger, Michael Heuser, Hans Kreipe, Karl Sotlar, Thomas Engleitner, Roland Rad, Wilko Weichert, Christian Peschel, Jürgen Ruland, Mathias Heikenwalder, Karsten Spiekermann, Julia Slotta-Huspenina, Olaf Groß, Philipp J Jost
Since acute myeloid leukemia (AML) is characterized by the blockade of hematopoietic differentiation and cell death, we interrogated RIPK3 signaling in AML development. Genetic loss of Ripk3 converted murine FLT3-ITD-driven myeloproliferation into an overt AML by enhancing the accumulation of leukemia-initiating cells (LIC). Failed inflammasome activation and cell death mediated by tumor necrosis factor receptor caused this accumulation of LIC exemplified by accelerated leukemia onset in Il1r1(-/-), Pycard(-/-), and Tnfr1/2(-/-) mice...
July 11, 2016: Cancer Cell
Susann Arvidsson, Britt-Mari Gilljam, Jens Nygren, Cornelia Maria Ruland, Trude Nordby-Bøe, Petra Svedberg
BACKGROUND: Children with cancer undergo intensive and long treatment periods that expose them and their families to a number of difficult physical, mental, and social challenges. Empowering children by actively involving them in their care can help them to cope with these challenges. It can, however, be difficult for children to be involved and talk about their illness experiences in a "traditional" conversation with health care professionals, especially for younger children. Sisom (Norwegian acronym "Si det som det er" or "Tell it how it is") is an interactive computer-based assessment and communication tool to give children (aged 6-12 years) with cancer a "voice" in their care...
2016: JMIR MHealth and UHealth
Tillmann Ruland, Man K Chan, Pawel Stocki, Laura Grosse, Matthias Rothermundt, Jason D Cooper, Volker Arolt, Sabine Bahn
RATIONALE: A substantial number of patients suffering from major depressive disorder (MDD) do not respond to multiple trials of anti-depressants, develop a chronic course of disease and become treatment resistant. Most of the studies investigating molecular changes in treatment-resistant depression (TRD) have only examined a limited number of molecules and genes. Consequently, biomarkers associated with TRD are still lacking. OBJECTIVES: This study aimed to use recently advanced high-throughput proteomic platforms to identify peripheral biomarkers of TRD defined by two staging models, the Thase and Rush staging model (TRM) and the Maudsley Staging Model (MSM)...
August 2016: Psychopharmacology
Aline Wuidart, Marielle Ousset, Steffen Rulands, Benjamin D Simons, Alexandra Van Keymeulen, Cédric Blanpain
Lineage tracing has become the method of choice to study the fate and dynamics of stem cells (SCs) during development, homeostasis, and regeneration. However, transgenic and knock-in Cre drivers used to perform lineage tracing experiments are often dynamically, temporally, and heterogeneously expressed, leading to the initial labeling of different cell types and thereby complicating their interpretation. Here, we developed two methods: the first one based on statistical analysis of multicolor lineage tracing, allowing the definition of multipotency potential to be achieved with high confidence, and the second one based on lineage tracing at saturation to assess the fate of all SCs within a given lineage and the "flux" of cells between different lineages...
June 1, 2016: Genes & Development
Waltraut M Merz, Anna M Rüland, Valeria Hippe, Bernd Poetzsch, Carsten Meyer, Joerg M Pollok, Ulrich Gembruch, Jonel Trebicka
Due to its rarity, experience with pregnancy in Budd-Chiari syndrome (BCS) is limited. With the advent of new treatment modalities, transjugular intrahepatic portosystemic shunt in particular, numbers of affected women seeking pregnancy with BCS are expected to rise. Here, we use a case that ended lethal within 2 years after delivery to discuss the effect of pregnancy on BCS and vice versa, and to highlight the necessity of a multidisciplinary teamwork. Additionally, a risk classification is proposed which may serve as a framework for preconception counseling and assist in the establishment and evaluation of treatment algorithms; its criteria need to be defined and assessed for their applicability in further studies...
May 2016: Medicine (Baltimore)
Marisa McGinley, Sarkis Morales-Vidal, Sean Ruland
Autoimmune encephalitis is associated with a wide variety of antibodies and clinical presentations. Voltage-gated potassium channel (VGKC) antibodies are a cause of autoimmune non-paraneoplastic encephalitis characterized by memory impairment, psychiatric symptoms, and seizures. We present a case of VGKC encephalitis likely preceding an ischemic stroke. Reports of autoimmune encephalitis associated with ischemic stroke are rare. Several hypotheses linking these two disease processes are proposed.
2016: Frontiers in Neurology
Argerie Tsimicalis, Sylvie Le May, Jennifer Stinson, Janet Rennick, Marie-France Vachon, Julie Louli, Sarah Bérubé, Stephanie Treherne, Sunmoo Yoon, Trude Nordby Bøe, Cornelia Ruland
Sisom is an interactive tool designed to help children communicate their cancer symptoms. Important design issues relevant to other cancer populations remain unexplored. This single-site, descriptive, qualitative study was conducted to linguistically validate Sisom with a group of French-speaking children with cancer, their parents, and health care professionals. The linguistic validation process included 6 steps: (1) forward translation, (2) backward translation, (3) patient testing, (4) production of a Sisom French version, (5) patient testing this version, and (6) production of the final Sisom French prototype...
May 25, 2016: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
Na Li, Lakshman Subrahmanyan, Emily Smith, Xiaoqing Yu, Samir Zaidi, Murim Choi, Shrikant Mane, Carol Nelson-Williams, Mohadesseh Bahjati, 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
Nonsyndromic patent ductus arteriosus (PDA) is a common congenital heart defect (CHD) with both inherited and acquired causes, but the disease mechanisms have remained elusive. Using combined genome-wide linkage analysis and whole-exome sequencing (WES), we identified independent mutations in PRDM6, which encodes a nuclear protein that is specific to vascular smooth muscle cells (VSMC), has histone methyl transferase activities, and acts as a transcriptional suppressor of contractile proteins. In vitro assays showed that the mutations cause loss of function either by intracellular redistribution of the protein and/or by alteration of its methyltransferase activities...
June 2, 2016: American Journal of Human Genetics
A Kuhn, A Landmann, N Patsinakidis, V Ruland, S Nozinic, A M Perusquía Ortiz, C Sauerland, T Luger, A Tsianakas, G Bonsmann
OBJECTIVE: The aim of the study was to assess the efficacy and safety of fumaric acid esters (FAEs) in patients with cutaneous lupus erythematosus (CLE). METHODS: In this 24-week, prospective, open-label, phase II pilot study, 11 patients with CLE, refractory to topical corticosteroids, were included. The primary endpoint of the study was the evaluation of the efficacy of FAEs after 24 weeks of treatment as assessed by the Revised Cutaneous Lupus Disease Area and Severity Index (RCLASI)...
October 2016: Lupus
Clio Rubinos, Sean Ruland
Complications involving the central and peripheral nervous system are frequently encountered in critically ill patients. All components of the neuraxis can be involved including the brain, spinal cord, peripheral nerves, neuromuscular junction, and muscles. Neurologic complications adversely impact outcome and length of stay. These complications can be related to underlying critical illness, pre-existing comorbid conditions, and commonly used and life-saving procedures and medications. Familiarity with the myriad neurologic complications that occur in the intensive care unit can facilitate their timely recognition and treatment...
June 2016: Current Neurology and Neuroscience Reports
Isabel Meininger, Richard A Griesbach, Desheng Hu, Torben Gehring, Thomas Seeholzer, Arianna Bertossi, Jan Kranich, Andrea Oeckinghaus, Andrea C Eitelhuber, Ute Greczmiel, Andreas Gewies, Marc Schmidt-Supprian, Jürgen Ruland, Thomas Brocker, Vigo Heissmeyer, Florian Heyd, Daniel Krappmann
MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4(+) T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion...
2016: Nature Communications
S Spinner, G Crispatzu, J-H Yi, E Munkhbaatar, P Mayer, U Höckendorf, N Müller, Z Li, T Schader, H Bendz, S Hartmann, M Yabal, K Pechloff, M Heikenwalder, G L Kelly, A Strasser, C Peschel, M-L Hansmann, J Ruland, U Keller, S Newrzela, M Herling, P J Jost
T lymphocyte non-Hodgkin's lymphoma (T-NHL) represents an aggressive and largely therapy-resistant subtype of lymphoid malignancies. As deregulated apoptosis is a frequent hallmark of lymphomagenesis, we analyzed gene expression profiles and protein levels of primary human T-NHL samples for various apoptotic regulators. We identified the apoptotic regulator MCL-1 as the only pro-survival BCL-2 family member to be highly expressed throughout all human T-NHL subtypes. Functional validation of pro-survival protein members of the BCL-2 family in two independent T-NHL mouse models identified that the partial loss of Mcl-1 significantly delayed T-NHL development in vivo...
July 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Tamás Németh, Krisztina Futosi, Cassian Sitaru, Jürgen Ruland, Attila Mócsai
Neutrophils are terminally differentiated cells with limited transcriptional activity. The biological function of their gene expression changes is poorly understood. CARD9 regulates transcription during antifungal immunity but its role in sterile inflammation is unclear. Here we show that neutrophil CARD9 mediates pro-inflammatory chemokine/cytokine but not lipid mediator release during non-infectious inflammation. Genetic deficiency of CARD9 suppresses autoantibody-induced arthritis and dermatitis in mice...
April 1, 2016: Nature Communications
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