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https://www.readbyqxmd.com/read/29136216/the-eukaryotic-linear-motif-resource-2018-update
#1
Marc Gouw, Sushama Michael, Hugo Sámano-Sánchez, Manjeet Kumar, András Zeke, Benjamin Lang, Benoit Bely, Lucía B Chemes, Norman E Davey, Ziqi Deng, Francesca Diella, Clara-Marie Gürth, Ann-Kathrin Huber, Stefan Kleinsorg, Lara S Schlegel, Nicolás Palopoli, Kim V Roey, Brigitte Altenberg, Attila Reményi, Holger Dinkel, Toby J Gibson
Short linear motifs (SLiMs) are protein binding modules that play major roles in almost all cellular processes. SLiMs are short, often highly degenerate, difficult to characterize and hard to detect. The eukaryotic linear motif (ELM) resource (elm.eu.org) is dedicated to SLiMs, consisting of a manually curated database of over 275 motif classes and over 3000 motif instances, and a pipeline to discover candidate SLiMs in protein sequences. For 15 years, ELM has been one of the major resources for motif research...
November 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29133554/what-is-resistance-impact-of-phenotypic-versus-molecular-drug-resistance-testing-on-multi-and-extensively-drug-resistant-tuberculosis-therapy
#2
Jan Heyckendorf, Sönke Andres, Claudio U Köser, Ioana D Olaru, Thomas Schön, Erik Sturegård, Patrick Beckert, Viola Schleusener, Thomas A Kohl, Doris Hillemann, Danesh Moradigaravand, Julian Parkhill, Sharon J Peacock, Stefan Niemann, Christoph Lange, Matthias Merker
Rapid and accurate drug-susceptibility testing (DST) is essential for the treatment of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using BACTEC 960 MGIT or Löwenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs.Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs: Hain GenoType MTBDRplus 2.0 and MTBDRsl 2...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29125874/pulmonary-immune-responses-to-mycobacterium-tuberculosis-in-exposed-individuals
#3
Christian Herzmann, Martin Ernst, Christoph Lange, Steffen Stenger, Stefan H E Kaufmann, Norbert Reiling, Tom Schaberg, Lize van der Merwe, Jeroen Maertzdorf
BACKGROUND: Blood based Interferon-(IFN)-γ release assays (IGRAs) have a poor predictive value for the development of tuberculosis. This study aimed to investigate the correlation between IGRAs and pulmonary immune responses in tuberculosis contacts in Germany. METHODS: IGRAs were performed on bronchoalveolar lavage (BAL) cells and peripheral blood from close healthy contacts of patients with culturally confirmed tuberculosis. Cellular BAL composition was determined by flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/29121945/potential-dosimetric-benefits-of-adaptive-tumor-tracking-over-the-internal-target-volume-concept-for-stereotactic-body-radiation-therapy-of-pancreatic-cancer
#4
Konstantina Karava, Stefanie Ehrbar, Oliver Riesterer, Johannes Roesch, Stefan Glatz, Stephan Klöck, Matthias Guckenberger, Stephanie Tanadini-Lang
BACKGROUND: Radiotherapy for pancreatic cancer has two major challenges: (I) the tumor is adjacent to several critical organs and, (II) the mobility of both, the tumor and its surrounding organs at risk (OARs). A treatment planning study simulating stereotactic body radiation therapy (SBRT) for pancreatic tumors with both the internal target volume (ITV) concept and the tumor tracking approach was performed. The two respiratory motion-management techniques were compared in terms of doses to the target volume and organs at risk...
November 9, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/29116426/high-resolution-language-mapping-of-broca-s-region-with-transcranial-magnetic-stimulation
#5
Katrin Sakreida, Inga Lange, Klaus Willmes, Stefan Heim, Ferdinand Binkofski, Hans Clusmann, Georg Neuloh
Broca's region, corresponding roughly to cytoarchitectonic areas 44 and 45 in the inferior frontal cortex, holds a multifunctional role in language processing, as shown, e.g., by functional imaging data. Neuro-navigated transcranial magnetic stimulation (TMS) enables complementary non-invasive mapping of cortical functions with high spatial resolution. Here, we report on detailed TMS language mapping of Broca's region in 12 healthy participants. The test protocol with an object naming task was adapted for high-resolution and semi-quantitative mapping of TMS-induced effects on speech and language performance...
November 7, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29103906/determination-of-the-influence-of-c24-d-2r-and-l-2s-isomers-of-the-cer-ap-on-the-lamellar-structure-of-stratum-corneum-model-systems-using-neutron-diffraction
#6
Thomas Schmitt, Stefan Lange, Stefan Sonnenberger, Bodo Dobner, Bruno Demé, Reinhard H H Neubert, Gert Gooris, Joke A Bouwstra
This study was able to investigate the different influence of the d- and l-ceramide [AP] on the lamellar as well as molecular nanostructure of stratum corneum simulating lipid model mixtures. In this case, neutron diffraction together with specifically deuterated ceramide was used as an effective tool to investigate the lamellar and the molecular nanostructure of the mixtures. It could clearly be demonstrated, that both isomers show distinctly different characteristics, even though the variation between both is only a single differently arranged OH-group...
November 4, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/29098143/architecture-and-prototypical-implementation-of-a-semantic-querying-system-for-big-earth-observation-image-bases
#7
Dirk Tiede, Andrea Baraldi, Martin Sudmanns, Mariana Belgiu, Stefan Lang
Spatiotemporal analytics of multi-source Earth observation (EO) big data is a pre-condition for semantic content-based image retrieval (SCBIR). As a proof of concept, an innovative EO semantic querying (EO-SQ) subsystem was designed and prototypically implemented in series with an EO image understanding (EO-IU) subsystem. The EO-IU subsystem is automatically generating ESA Level 2 products (scene classification map, up to basic land cover units) from optical satellite data. The EO-SQ subsystem comprises a graphical user interface (GUI) and an array database embedded in a client server model...
2017: Eur J Remote Sens
https://www.readbyqxmd.com/read/29073886/ultra-high-field-swi-of-the-substantia-nigra-at-7t-reliability-and-consistency-of-the-swallow-tail-sign
#8
Manuel A Schmidt, Tobias Engelhorn, Franz Marxreiter, Juergen Winkler, Stefan Lang, Stephan Kloska, Philipp Goelitz, Arnd Doerfler
BACKGROUND: The loss of the swallow-tail sign of the substantia nigra has been proposed for diagnosis of Parkinson's disease. Aim was to evaluate, if the sign occurs consistently in healthy subjects and if it can be reliably detected with high-resolution 7T susceptibility weighted imaging (SWI). METHODS: Thirteen healthy adults received SWI at 7T. 3 neuroradiologists, who were blinded to patients' diagnosis, independently classified subjects regarding the swallow-tail sign to be present or absent...
October 26, 2017: BMC Neurology
https://www.readbyqxmd.com/read/29058307/genetic-immunization-with-mouse-thyrotropin-hormone-receptor-plasmid-breaks-self-tolerance-for-a-murine-model-of-autoimmune-thyroid-disease-and-graves-orbitopathy
#9
Anke Schlüter, Mareike Horstmann, Salvador Diaz-Cano, Svenja Plöhn, Kerstin Stähr, Stefan Mattheis, Michael Oeverhaus, Stephan Lang, Ulrich Flögel, Utta Berchner-Pfannschmidt, Anja Eckstein, J Paul Banga
Experimental models of Graves' hyperthyroid disease accompanied by Graves' orbitopathy (GO) can be efficiently induced in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. In this study, we report on the development of a bona fide murine model of autoimmune Graves' disease induced with homologous mouse TSHR A-subunit plasmid. Autoimmune thyroid disease in the self-antigen model was accompanied by GO and characterized by histopathology of hyperplastic glands with large thyroid follicular cells...
October 23, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29053901/familial-hypercholesterolaemia-in-patients-with-ischemic-stroke-or-transient-ischemic-attack
#10
Thomas Toell, Lukas Mayer, Raimund Pechlaner, Stefan Krebs, Karin Willeit, Clemens Lang, Christian Boehme, Barbara Prantl, Michael Knoflach, Julia Ferrari, Philipp Fuchs, Wolfgang Prokop, Andrea Griesmacher, Wilfried Lang, Stefan Kiechl, Johann Willeit
BACKGROUND AND AIMS: Identification of patients with familial hypercholesterolemia (FH) is a prerequisite for the appropriate management of their excess cardiovascular risk. It is currently unknown how many patients with acute ischemic stroke or transient ischemic attack (TIA) are affected by FH and whether systematic screening for FH is warranted in these patients. METHODS: The prevalence of a clinical diagnosis of FH was estimated in a large representative series of patients with acute ischemic stroke or TIA (ABCD2 score ≥3) using the Dutch Lipid Clinic Network Algorithm (DLCNA; possible FH ≥3, probable/definite FH ≥6)...
October 20, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29050560/the-pcsk9-ldl-receptor-axis-and%C3%A2-outcomes-in-heart-failure-biostat-chf-subanalysis
#11
MULTICENTER STUDY
Antoni Bayes-Genis, Julio Núñez, Faiez Zannad, João Pedro Ferreira, Stefan D Anker, John G Cleland, Kenneth Dickstein, Gerasimos Filippatos, Chim C Lang, Leong L Ng, Piotr Ponikowski, Nilesh J Samani, Dirk J van Veldhuisen, Aeilko H Zwinderman, Marco Metra, Josep Lupón, Adriaan A Voors
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression. OBJECTIVES: The aim of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with heart failure (HF). METHODS: The BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational, prospective, observational study that included patients with worsening HF signs and/or symptoms...
October 24, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29050239/application-of-in-vivo-imaging-techniques-to-monitor-therapeutic-efficiency-of-plx4720-in-an-experimental-model-of-microsatellite-instable-colorectal-cancer
#12
Sarah Rohde, Tobias Lindner, Stefan Polei, Jan Stenzel, Luise Borufka, Sophie Achilles, Eric Hartmann, Falko Lange, Claudia Maletzki, Michael Linnebacher, Änne Glass, Sarah Marie Schwarzenböck, Jens Kurth, Alexander Hohn, Brigitte Vollmar, Bernd Joachim Krause, Robert Jaster
OBJECTIVES: Patient-derived tumor cell lines are a powerful tool to analyze the sensitivity of individual tumors to specific therapies in mice. An essential prerequisite for such an approach are reliable quantitative techniques to monitor tumor progression in vivo. METHODS: We have employed HROC24 cells, grown heterotopically in NMRI Foxn1(nu) mice, as a model of microsatellite instable colorectal cancer to investigate the therapeutic efficiencies of 5'-fluorouracil (5'-FU) and the mutant BRAF inhibitor PLX4720, a vemurafenib analogue, by three independent methods: external measurement by caliper, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29040648/molecular-basis-for-asymmetry-sensing-of-sirnas-by-the-drosophila-loqs-pd-dcr-2-complex-in-rna-interference
#13
Jan-Niklas Tants, Stephanie Fesser, Thomas Kern, Ralf Stehle, Arie Geerlof, Christoph Wunderlich, Michael Juen, Christoph Hartlmüller, Romy Böttcher, Stefan Kunzelmann, Oliver Lange, Christoph Kreutz, Klaus Förstemann, Michael Sattler
RNA interference defends against RNA viruses and retro-elements within an organism's genome. It is triggered by duplex siRNAs, of which one strand is selected to confer sequence-specificity to the RNA induced silencing complex (RISC). In Drosophila, Dicer-2 (Dcr-2) and the double-stranded RNA binding domain (dsRBD) protein R2D2 form the RISC loading complex (RLC) and select one strand of exogenous siRNAs according to the relative thermodynamic stability of base-pairing at either end. Through genome editing we demonstrate that Loqs-PD, the Drosophila homolog of human TAR RNA binding protein (TRBP) and a paralog of R2D2, forms an alternative RLC with Dcr-2 that is required for strand choice of endogenous siRNAs in S2 cells...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29037960/effect-of-procalcitonin-guided-antibiotic-treatment-on-mortality-in-acute-respiratory-infections-a-patient-level-meta-analysis
#14
Philipp Schuetz, Yannick Wirz, Ramon Sager, Mirjam Christ-Crain, Daiana Stolz, Michael Tamm, Lila Bouadma, Charles E Luyt, Michel Wolff, Jean Chastre, Florence Tubach, Kristina B Kristoffersen, Olaf Burkhardt, Tobias Welte, Stefan Schroeder, Vandack Nobre, Long Wei, Heiner C Bucher, Djillali Annane, Konrad Reinhart, Ann R Falsey, Angela Branche, Pierre Damas, Maarten Nijsten, Dylan W de Lange, Rodrigo O Deliberato, Carolina F Oliveira, Vera Maravić-Stojković, Alessia Verduri, Bianca Beghé, Bin Cao, Yahya Shehabi, Jens-Ulrik S Jensen, Caspar Corti, Jos A H van Oers, Albertus Beishuizen, Armand R J Girbes, Evelien de Jong, Matthias Briel, Beat Mueller
BACKGROUND: In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. METHODS: Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control...
October 13, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29037780/bio-based-succinate-from-sucrose-high-resolution-13-c-metabolic-flux-analysis-and-metabolic-engineering-of-the-rumen-bacterium-basfia-succiniciproducens
#15
Anna Lange, Judith Becker, Dennis Schulze, Edern Cahoreau, Jean-Charles Portais, Stefan Haefner, Hartwig Schröder, Joanna Krawczyk, Oskar Zelder, Christoph Wittmann
Succinic acid is a platform chemical of recognized industrial value and accordingly faces a continuous challenge to enable manufacturing from most attractive raw materials. It is mainly produced from glucose, using microbial fermentation. Here, we explore and optimize succinate production from sucrose, a globally applied substrate in biotechnology, using the rumen bacterium Basfia succiniciproducens DD1. As basis of the strain optimization, the yet unknown sucrose metabolism of the microbe was studied, using (13)C metabolic flux analyses...
October 14, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29030339/muscle-%C3%AE-adrenergic-responsiveness-during-exercise-and-atp-induced-vasodilation-in-chronic-obstructive-pulmonary-disease-patients
#16
Ulrik Winning Iepsen, Gregers Druedal Wibe Munch, Camilla Koch Ryrsø, Niels H Secher, Peter Lange, Pia Thaning, Bente Klarlund Pedersen, Stefan P Mortensen
Sympathetic vasoconstriction is blunted in exercising muscle (functional sympatholysis) but becomes attenuated with age. We tested the hypothesis that functional sympatholysis is further impaired in chronic obstructive pulmonary disease (COPD) patients. We determined leg blood flow (LBF) and calculated leg vascular conductance (LVC) during 1) femoral-arterial Tyramine infusion (evokes endogenous norepinephrine release; 1 µmol min(-1) kg leg mass(-1)); 2) one-legged knee-extensor exercise with and without Tyramine infusion (10 W and 20% of maximal workload (WLmax)); 3) ATP (0...
October 13, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29025194/procalcitonin-to-initiate-or-discontinue-antibiotics-in-acute-respiratory-tract-infections
#17
REVIEW
Philipp Schuetz, Yannick Wirz, Ramon Sager, Mirjam Christ-Crain, Daiana Stolz, Michael Tamm, Lila Bouadma, Charles E Luyt, Michel Wolff, Jean Chastre, Florence Tubach, Kristina B Kristoffersen, Olaf Burkhardt, Tobias Welte, Stefan Schroeder, Vandack Nobre, Long Wei, Heiner C Bucher, Neera Bhatnagar, Djillali Annane, Konrad Reinhart, Angela Branche, Pierre Damas, Maarten Nijsten, Dylan W de Lange, Rodrigo O Deliberato, Stella Ss Lima, Vera Maravić-Stojković, Alessia Verduri, Bin Cao, Yahya Shehabi, Albertus Beishuizen, Jens-Ulrik S Jensen, Caspar Corti, Jos A Van Oers, Ann R Falsey, Evelien de Jong, Carolina F Oliveira, Bianca Beghe, Matthias Briel, Beat Mueller
BACKGROUND: Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units...
October 12, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29017690/the-range-and-scientific-value-of-randomized-trials
#18
Stefan Lange, Stefan Sauerland, Jörg Lauterberg, Jürgen Windeler
BACKGROUND: The randomized, controlled trial (RCT) is the gold standard of scientific evidence for the attribution of clinical effects (benefits and harms) to medical interventions. Many different designs for RCTs have been developed in order to counter legitimate critical objections and to better adapt the trials to the continually changing challenges that face clinical research. METHODS: The diversity and adaptability of randomized trial designs are presented and discussed on the basis of a selective literature review and specific illustrative examples...
September 22, 2017: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/28993162/stability-of-spinal-bone-lesions-in-patients-with-multiple-myeloma-after-radiotherapy-a-retrospective-analysis-of-130-cases
#19
Kristin Lang, Laila König, Thomas Bruckner, Robert Förster, Tanja Sprave, Ingmar Schlampp, Tilman Bostel, Stefan Welte, Nils H Nicolay, Jürgen Debus, Harald Rief
BACKGROUND: The objective of the present retrospective analysis was the response evaluation regarding bone density and stability of patients with osteolytic spinal bone lesions due to multiple myeloma after palliative radiotherapy (RT). PATIENTS AND METHODS: Patients with multiple myeloma who had undergone spinal RT from March 2003 to May 2016 were analyzed before and 3 and 6 months after RT. Assessment of spinal stability and bone density was performed using the internationally recognized Taneichi scoring system and measurement of bone density using computed tomography imaging-based Hounsfield units...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28985499/measurement-of-backbone-hydrogen-deuterium-exchange-in-the-type-iii-secretion-system-needle-protein-prgi-by-solid-state-nmr
#20
Veniamin Chevelkov, Karin Giller, Stefan Becker, Adam Lange
In this report we present site-specific measurements of amide hydrogen-deuterium exchange rates in a protein in the solid state phase by MAS NMR. Employing perdeuteration, proton detection and a high external magnetic field we could adopt the highly efficient Relax-EXSY protocol previously developed for liquid state NMR. According to this method, we measured the contribution of hydrogen exchange on apparent (15)N longitudinal relaxation rates in samples with differing D2O buffer content. Differences in the apparent T1 times allowed us to derive exchange rates for multiple residues in the type III secretion system needle protein...
October 2017: Journal of Magnetic Resonance
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