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Garima Garg, Andreas Muschaweckh, Helena Moreno, Ajithkumar Vasanthakumar, Stefan Floess, Gildas Lepennetier, Rupert Oellinger, Yifan Zhan, Tommy Regen, Michael Hiltensperger, Christian Peter, Lilian Aly, Benjamin Knier, Lakshmi Reddy Palam, Reuben Kapur, Mark H Kaplan, Ari Waisman, Roland Rad, Gunnar Schotta, Jochen Huehn, Axel Kallies, Thomas Korn
Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and "toxic" gain-of-function of Treg cells in the inflamed CNS...
February 12, 2019: Cell Reports
Irena Roci, Jeramie D Watrous, Kim A Lagerborg, Lorenzo Lafranchi, Arne Lindqvist, Mohit Jain, Roland Nilsson
Alterations in cell-cycle regulation and cellular metabolism are associated with cancer transformation, and enzymes active in the committed cell-cycle phase may represent vulnerabilities of cancer cells. Here, we map metabolic events in the G1 and SG2 M phases by combining cell sorting with mass spectrometry-based isotope tracing, revealing hundreds of cell-cycle-associated metabolites. In particular, arginine uptake and ornithine synthesis are active during SG2 M in transformed but not in normal cells, with the mitochondrial arginase 2 (ARG2) enzyme as a potential mechanism...
February 12, 2019: Cell Reports
Sarah L Sayner, Chung-Sik Choi, Marcy E Maulucci, Ramila Kc, Chun Zhou, April K Scruggs, Thomas Yarbrough, Leslie Anne Hargett Blair, Judy A C King, Roland Seifert, Volkhard Kaever, Natalie N Bauer
The second messenger, cAMP, is highly compartmentalized to facilitate signaling specificity. Extracellular vesicles (EVs) are submicron, intact vesicles released from many cell types that can act as biomarkers or be involved in cell-to-cell communication. While it is well recognized that EVs encapsulate functional proteins and RNAs/miRNAs, currently it is unclear whether cyclic nucleotides are encapsulated within EVs to provide an additional second messenger compartment. Using ultracentrifugation, EVs were isolated from the culture medium of unstimulated systemic and pulmonary endothelial cells...
February 13, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
Alexis Laugerette, Benedikt J Schwaiger, Kevin Brown, Lena C Frerking, Felix K Kopp, Kai Mei, Thorsten Sellerer, Jan Kirschke, Thomas Baum, Alexandra S Gersing, Daniela Pfeiffer, Alexander A Fingerle, Ernst J Rummeny, Roland Proksa, Peter B Noël, Franz Pfeiffer
OBJECTIVES: To develop and evaluate a method for areal bone mineral density (aBMD) measurement based on dual-layer spectral CT scout scans. METHODS: A post-processing algorithm using a pair of 2D virtual mono-energetic scout images (VMSIs) was established in order to semi-automatically compute the aBMD at the spine similarly to DXA, using manual soft tissue segmentation, semi-automatic segmentation for the vertebrae, and automatic segmentation for the background...
February 13, 2019: European Radiology
Victor M Schuettfort, Jessica Schoof, Clemens M Rosenbaum, Tim A Ludwig, Malte W Vetterlein, Sami-Ramzi Leyh-Bannurah, Valentin Maurer, Christian P Meyer, Roland Dahlem, Margit Fisch, Christoph-Philip Reiss
PURPOSE: The international meeting on reconstructive Urology (IMORU) is a live surgery event (LSE) where expert surgeons perform various reconstructive surgeries. To evaluate patient safety, an extended follow-up of the complications of two subsequent IMORU meetings were gathered. Also, a detailed survey concerning the participant's assessment of the educational benefit was performed. METHODS: All patients that were operated during the IMORU V and VI were included...
February 11, 2019: World Journal of Urology
Alexander Wutzler, Christos Krogias, Anna Grau, Roland Veltkamp, Peter U Heuschmann, Karl Georg Haeusler
BACKGROUND: Atrial fibrillation (AF) is present in 15-20% of patients with acute ischemic stroke. Oral anticoagulation reduces the risk of AF-related recurrent stroke but clinical guideline recommendations are rather vague regarding its use in the acute phase of stroke. We aimed to assess the current clinical practice of medical stroke prevention in AF patients during the acute phase of ischemic stroke. METHODS: In April 2017, a standardized anonymous questionnaire was sent to clinical leads of all 298 certified stroke units in Germany...
February 12, 2019: BMC Neurology
Judith E Grolleman, Richarda M de Voer, Fadwa A Elsayed, Maartje Nielsen, Robbert D A Weren, Claire Palles, Marjolijn J L Ligtenberg, Janet R Vos, Sanne W Ten Broeke, Noel F C C de Miranda, Renske A Kuiper, Eveline J Kamping, Erik A M Jansen, M Elisa Vink-Börger, Isabell Popp, Alois Lang, Isabel Spier, Robert Hüneburg, Paul A James, Na Li, Marija Staninova, Helen Lindsay, David Cockburn, Olivera Spasic-Boskovic, Mark Clendenning, Kevin Sweet, Gabriel Capellá, Wenche Sjursen, Hildegunn Høberg-Vetti, Marjolijn C Jongmans, Kornelia Neveling, Ad Geurts van Kessel, Hans Morreau, Frederik J Hes, Rolf H Sijmons, Hans K Schackert, Clara Ruiz-Ponte, Dagmara Dymerska, Jan Lubinski, Barbara Rivera, William D Foulkes, Ian P Tomlinson, Laura Valle, Daniel D Buchanan, Sue Kenwrick, Julian Adlard, Aleksandar J Dimovski, Ian G Campbell, Stefan Aretz, Detlev Schindler, Tom van Wezel, Nicoline Hoogerbrugge, Roland P Kuiper
Biallelic germline mutations affecting NTHL1 predispose carriers to adenomatous polyposis and colorectal cancer, but the complete phenotype is unknown. We describe 29 individuals carrying biallelic germline NTHL1 mutations from 17 families, of which 26 developed one (n = 10) or multiple (n = 16) malignancies in 14 different tissues. An unexpected high breast cancer incidence was observed in female carriers (60%). Mutational signature analysis of 14 tumors from 7 organs revealed that NTHL1 deficiency underlies the main mutational process in all but one of the tumors (93%)...
February 11, 2019: Cancer Cell
Shyra Wilde, Yanlong Jiang, Amanda M Tafoya, Jamie Horsman, Miranda Yousif, Luis Armando Vazquez, Kenneth L Roland
Necrotic enteritis is an economically important poultry disease caused by the bacterium Clostridium perfringens. There are currently no necrotic enteritis vaccines commercially available for use in broiler birds, the most important target population. Salmonella-vectored vaccines represent a convenient and effective option for controlling this disease. We used a single attenuated Salmonella vaccine strain, engineered to lyse within the host, to deliver up to three C. perfringens antigens. Two of the antigens were toxoids, based on C...
2019: PloS One
Michael Bacht, Mika T Tarkka, Ivan Fernandez-Lopez, Markus Bönn, Roland Brandl, François Buscot, Lasse Feldhahn, Thorsten Grams, Sylvie Herrmann, Martin Schädler
Herbivores and mycorrhizal fungi interactively influence the growth, resource utilization, and plant defense responses. We studied these interactions in a tri-trophic system comprising Quercus robur, the herbivore Lymantria dispar and the ectomycorrhizal fungus Piloderma croceum under controlled laboratory conditions at the levels of gene expression and carbon/nitrogen allocation. Taking advantage of the endogenous rhythmic growth displayed by oaks, we thereby compared gene transcript abundances and resource shifts during shoot growth with those during the alternating root growth flushes...
February 12, 2019: Molecular Plant-microbe Interactions: MPMI
Ariele L Greenfield, Ravi Dandekar, Akshaya Ramesh, Erica L Eggers, Hao Wu, Sarah Laurent, William Harkin, Natalie S Pierson, Martin S Weber, Roland G Henry, Antje Bischof, Bruce Ac Cree, Stephen L Hauser, Michael R Wilson, H-Christian von Büdingen
B-cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related B-cells exist in the cerebrospinal fluid (CSF), meninges, and central nervous system (CNS) parenchyma of MS patients. We sought to investigate the presence of clonally related B-cells over time by performing immunoglobulin heavy chain variable region repertoire sequencing on B-cells from longitudinally collected blood and CSF samples of MS patients (n=10). All patients were untreated at the time of the initial sampling; the majority (n=7) were treated with immune modulating therapies 1...
February 12, 2019: JCI Insight
Xaver Feichtinger, Roland Kocijan, Rainer Mittermayr, Andreas Baierl, Jakob Schanda, Robert Wakolbinger, Heinrich Resch, Christian Fialka, Christian Muschitz
INTRODUCTION: Multiple fractures are of high clinical relevance, as a significant increase in mortality rate has been described. The purpose of this study was to evaluate differences in age and gender distribution in multiple fractures dependent on severity of trauma. Furthermore, affected anatomic regions and frequently associated fracture regions were investigated. METHODS: Patients who had sustained multiple fractures between 2000 and 2012 were included in this study...
February 12, 2019: European Journal of Trauma and Emergency Surgery: Official Publication of the European Trauma Society
Stanislas C Morand, Morgane Bertignac, Agnes Iltis, Iris C R M Kolder, Walter Pirovano, Roland Jourdain, Cécile Clavaud
Malassezia restricta, one of the predominant basidiomycetous yeasts present on human skin, is involved in scalp disorders. Here, we report the complete genome sequence of the lipophilic Malassezia restricta CBS 7877 strain, which will facilitate the study of the mechanisms underlying its commensal and pathogenic roles within the skin microbiome.
February 2019: Microbiology resource announcements
Selina K Kaiser, Ronghe Lin, Sharon Mitchell, Edvin Fako, Frank Krumeich, Roland Hauert, Olga V Safonova, Vita A Kondratenko, Evgenii V Kondratenko, Sean M Collins, Paul A Midgley, Núria López, Javier Pérez-Ramírez
Carbon-supported gold catalysts have the potential to replace the toxic mercuric chloride-based system applied industrially for acetylene hydrochlorination, a key technology for the manufacture of polyvinyl chloride. However, the design of an optimal catalyst is essentially hindered by the difficulties in assessing the nature of the active site. Herein, we present a platform of carbon supported gold nanostructures at a fixed metal loading, ranging from single atoms of tunable oxidation state and coordination to metallic nanoparticles, by varying the structure of functionalised carbons and use of thermal activation...
January 14, 2019: Chemical Science
Anny-Claude Luissint, Holly C Williams, Wooki Kim, Sven Flemming, Veronica Azcutia, Roland S Hilgarth, Monique N O' Leary, Timothy L Denning, Asma Nusrat, Charles A Parkos
Junctional adhesion molecule-A (JAM-A) is a transmembrane glycoprotein expressed on leukocytes, endothelia, and epithelia that regulates biological processes including barrier function and immune responses. While JAM-A has been reported to facilitate tissue infiltration of leukocytes under inflammatory conditions, the contributions of leukocyte-expressed JAM-A in vivo remain unresolved. We investigated the role of leukocyte-expressed JAM-A in acute peritonitis induced by zymosan, lipopolysaccharide (LPS), or TNFα using mice with selective loss of JAM-A in myelomonocytic cells (LysM-Cre;Jam-afl/fl )...
February 11, 2019: Mucosal Immunology
Shoshana J Wodak, Emanuele Paci, Nikolay V Dokholyan, Igor N Berezovsky, Amnon Horovitz, Jing Li, Vincent J Hilser, Ivet Bahar, John Karanicolas, Gerhard Stock, Peter Hamm, Roland H Stote, Jerome Eberhardt, Yassmine Chebaro, Annick Dejaegere, Marco Cecchini, Jean-Pierre Changeux, Peter G Bolhuis, Jocelyne Vreede, Pietro Faccioli, Simone Orioli, Riccardo Ravasio, Le Yan, Carolina Brito, Matthieu Wyart, Paraskevi Gkeka, Ivan Rivalta, Giulia Palermo, J Andrew McCammon, Joanna Panecka-Hofman, Rebecca C Wade, Antonella Di Pizio, Masha Y Niv, Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang, Dzmitry Padhorny, Dima Kozakov, Tom McLeish
Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems...
January 17, 2019: Structure
Karl Roland Ehrenberg, Jianpeng Gao, Felix Oppel, Stephanie Frank, Na Kang, Sebastian M Dieter, Friederike Herbst, Lino Möhrmann, Taronish D Dubash, Erik R Schulz, Hendrik Strakerjahn, Klara M Giessler, Sarah Weber, Ava Oberlack, Eva-Maria Rief, Oliver Strobel, Frank Bergmann, Felix Lasitschka, Jürgen Weitz, Hanno Glimm, Claudia R Ball
In highly aggressive malignancies like pancreatic cancer (PC), patient-derived tumor models can serve as disease-relevant models to understand disease-related biology as well as to guide clinical decision-making. In this study, we describe a two-step protocol allowing systematic establishment of patient-derived primary cultures from PC patient tumors. Initial xenotransplantation of surgically resected patient tumors (n = 134) into immunodeficient mice allows for efficient in vivo expansion of vital tumor cells and successful tumor expansion in 38% of patient tumors (51/134)...
February 10, 2019: Cells
Zoltán Bánki, Roland Werner, Lydia Riepler, Annika Rössler, Brigitte Müllauer, Verena Hegen, Wibke Bayer, J Sjef Verbeek, Ulf Dittmer, Heribert Stoiber
Dendritic cells (DCs) express Fcγ receptors (FcγRs) for the binding immune complexes (ICs) consisting of IgG and antigens (Ags). IC⁻FcγR interactions have been demonstrated to enhance activation and antigen-presenting functions of DCs. Utilizing Friend virus (FV), an oncogenic mouse retrovirus, we investigated the effect of IgG-opsonization of retroviral particles on the infection of DCs and the subsequent presentation of viral antigens by DCs to virus-specific CD8 T cells. We found that opsonization by virus-specific non-neutralizing IgG abrogated DC infection and as a consequence significantly reduced the capacity of DCs to activate virus-specific CD8 T cells...
February 8, 2019: Viruses
Stephan Debus, Roland Posner
Giving appointments to semiotics and social psychiatry the framework of semiotics is characterized with regard to fields of application in social psychiatry. From that point an interdisciplinary cooperation could be achieved with benefit for both sides. By means of the theory of semiosis (sign process) it could be shown, in which way the communicative meaning of all speech acts (illocutionary forces) could be formally represented. Against this background the SRZP-research concepts of structure (PART II), dynamics (PART III) and modelling (PART V) of jeopardizing situations could be unfolded retrospectively...
March 2019: Psychiatrische Praxis
José Ferreira Penêda, Sandra Alves, Francisco Monteiro, Inês Sousa Ribeiro, Nuno Barros Lima, Artur Condé
The authors present the case of a 5-year-old girl referred to our institution due to several episodes of nocturnal stridor with ocular retroversion and parental notion of apnea. She has been previously submitted to adenotonsillectomy. Due to symptoms worsening she was referred to our hospital. Here, a nasal fiberoptic endoscopy evaluation was conducted and a diagnosis of laryngomalacia was done. The was submitted to CO2 laser ariepiglotoplasty with symptom improvement after surgery. During a follow-up appointment, parents reported self-limited clonic facial movements at sleep onset...
January 30, 2019: International Journal of Pediatric Otorhinolaryngology
Ece Bayram, Brent Bluett, Xiaowei Zhuang, Dietmar Cordes, Denise R LaBelle, Sarah J Banks
OBJECTIVE: Cognitive decline is common in Parkinson's disease (PD), but changes can occur in a variety of cognitive domains. The lack of a single cognitive phenotype complicates diagnosis and tracking. In an earlier study we used a data-driven approach to identify distinct cognitive phenotypes of early PD. Here we identify the morphometric brain differences between those different phenotypes compared with cognitively normal PD participants. METHODS: Six different cognitive classes were included (Weak, Typical, Weak-Visuospatial/Strong-Memory, Weak-Visuospatial, Amnestic, Strong)...
February 7, 2019: Journal of the Neurological Sciences
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