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Tales Rocha de Moura, Sina Mozaffari-Jovin, Csaba Zoltán Kibédi Szabó, Jana Schmitzová, Olexandr Dybkov, Constantin Cretu, Michael Kachala, Dmitri Svergun, Henning Urlaub, Reinhard Lührmann, Vladimir Pena
Human nineteen complex (NTC) acts as a multimeric E3 ubiquitin ligase in DNA repair and splicing. The transfer of ubiquitin is mediated by Prp19-a homotetrameric component of NTC whose elongated coiled coils serve as an assembly axis for two other proteins called SPF27 and CDC5L. We find that Prp19 is inactive on its own and have elucidated the structural basis of its autoinhibition by crystallography and mutational analysis. Formation of the NTC core by stepwise assembly of SPF27, CDC5L, and PLRG1 onto the Prp19 tetramer enables ubiquitin ligation...
March 15, 2018: Molecular Cell
Yunuen Avalos-Padilla, Roland L Knorr, Rosario Javier-Reyna, Guillermina García-Rivera, Reinhard Lipowsky, Rumiana Dimova, Esther Orozco
The endosomal sorting complex required for transport (ESCRT) orchestrates cell membrane-remodeling mechanisms in eukaryotes, including endocytosis. However, ESCRT functions in phagocytosis (ingestion of ≥250 nm particles), has been poorly studied. In macrophages and amoebae, phagocytosis is required for cell nutrition and attack to other microorganisms and cells. In Entamoeba histolytica , the voracious protozoan responsible for human amoebiasis, phagocytosis is a land mark of virulence. Here, we have investigated the role of ESCRT-III in the phagocytosis of E...
2018: Frontiers in Cellular and Infection Microbiology
Daniel Rettenwander, Reinhard Wagner, Andreas Reyer, Maximilian Bonta, Lei Cheng, Marca M Doeff, Andreas Limbeck, Martin Wilkening, Georg Amthauer
The interface stability versus Li represents a major challenge in the development of next-generation all-solid-state batteries (ASSB), which take advantage of the inherently safe ceramic electrolytes. Cubic Li7 La3 Zr2 O12 garnets represent the most promising electrolytes for this technology. The high interfacial impedance versus Li is, however, still a bottleneck toward future devices. Herein, we studied the electrochemical performance of Fe3+ -stabilized Li7 La3 Zr2 O12 (LLZO:Fe) versus Li metal and found a very high total conductivity of 1...
February 22, 2018: Journal of Physical Chemistry. C, Nanomaterials and Interfaces
Nina Zila, Andrea Bileck, Besnik Muqaku, Lukas Janker, Ossia M Eichhoff, Phil F Cheng, Reinhard Dummer, Mitchell P Levesque, Christopher Gerner, Verena Paulitschke
Background: MAP kinase inhibitor (MAPKi) therapy for BRAF mutated melanoma is characterized by high response rates but development of drug resistance within a median progression-free survival (PFS) of 9-12 months. Understanding mechanisms of resistance and identifying effective therapeutic alternatives is one of the most important scientific challenges in melanoma. Using proteomics, we want to specifically gain insight into the pathophysiological process of cerebral metastases. Methods: Cerebral metastases from melanoma patients were initially analyzed by a LC-MS shotgun approach performed on a QExactive HF hybrid quadrupole-orbitrap mass spectrometer...
2018: Clinical Proteomics
Reinhard Schweitzer-Stenner, Siobhan E Toal
Growing evidence suggests that the conformational distributions of amino acid residues in unfolded peptides and proteins depend on the nature of the nearest neighbors. To explore whether the underlying interactions would lead to a breakdown of the isolated pair hypothesis of the classical random coil model, we further analyzed the conformational propensities that were recently obtained for the two guest residues (x,y) of GxyG tetrapeptides. We constructed a statistical thermodynamics model that allows for cooperative as well as for anticooperative interactions between adjacent residues adopting either a polyproline II or a β-strand conformation...
March 13, 2018: Biophysical Journal
Julie George, Vonn Walter, Martin Peifer, Ludmil B Alexandrov, Danila Seidel, Frauke Leenders, Lukas Maas, Christian Müller, Ilona Dahmen, Tiffany M Delhomme, Maude Ardin, Noemie Leblay, Graham Byrnes, Ruping Sun, Aurélien De Reynies, Anne McLeer-Florin, Graziella Bosco, Florian Malchers, Roopika Menon, Janine Altmüller, Christian Becker, Peter Nürnberg, Viktor Achter, Ulrich Lang, Peter M Schneider, Magdalena Bogus, Matthew G Soloway, Matthew D Wilkerson, Yupeng Cun, James D McKay, Denis Moro-Sibilot, Christian G Brambilla, Sylvie Lantuejoul, Nicolas Lemaitre, Alex Soltermann, Walter Weder, Verena Tischler, Odd Terje Brustugun, Marius Lund-Iversen, Åslaug Helland, Steinar Solberg, Sascha Ansén, Gavin Wright, Benjamin Solomon, Luca Roz, Ugo Pastorino, Iver Petersen, Joachim H Clement, Jörg Sänger, Jürgen Wolf, Martin Vingron, Thomas Zander, Sven Perner, William D Travis, Stefan A Haas, Magali Olivier, Matthieu Foll, Reinhard Büttner, David Neil Hayes, Elisabeth Brambilla, Lynnette Fernandez-Cuesta, Roman K Thomas
Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: "type I LCNECs" with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and "type II LCNECs" enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC...
March 13, 2018: Nature Communications
Kristina Glenske, Phil Donkiewicz, Alexander Köwitsch, Nada Milosevic-Oljaca, Patrick Rider, Sven Rofall, Jörg Franke, Ole Jung, Ralf Smeets, Reinhard Schnettler, Sabine Wenisch, Mike Barbeck
The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum . In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials...
March 12, 2018: International Journal of Molecular Sciences
Christiane Graetz, Adriane Gröger, Felix Luessi, Anke Salmen, Daniela Zöller, Janine Schultz, Nelly Siller, Vinzenz Fleischer, Barbara Bellenberg, Achim Berthele, Viola Biberacher, Joachim Havla, Michael Hecker, Reinhard Hohlfeld, Carmen Infante-Duarte, Jan S Kirschke, Tania Kümpfel, Ralf Linker, Friedemann Paul, Steffen Pfeuffer, Philipp Sämann, Gerrit Toenges, Frank Weber, Uwe K Zettl, Antje Jahn-Eimermacher, Gisela Antony, Sergiu Groppa, Heinz Wiendl, Bernhard Hemmer, Mark Mühlau, Carsten Lukas, Ralf Gold, Christina M Lill, Frauke Zipp
BACKGROUND: The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors. OBJECTIVE: The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course. METHODS: Untreated patients ( n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI)...
March 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Jessica G Rushton, Reinhard Ertl, Dieter Klein, Alexander Tichy, Barbara Nell
Objectives Feline diffuse iris melanoma (FDIM) is the most common malignant primary intraocular tumour in cats, with reported metastases rates between 19% and 63%. Currently, the only available diagnostic tool for a tentative diagnosis is histopathological examination of the enucleated eye. Therefore, the veterinary ophthalmologist is often faced with the dilemma of whether to enucleate an oftentimes visual eye or to continue monitoring, with the risk of metastases developing. In the past, cell-free DNA (cfDNA) gained more attention in human medicine, especially in the field of oncology...
March 1, 2018: Journal of Feline Medicine and Surgery
Stephan Prinz, Matthias Häfner, Marcel Schultze, Catherine Y Teisset, Robert Bessing, Knut Michel, Reinhard Kienberger, Thomas Metzger
In the original manuscript, a residual RMS timing jitter below 2 fs between pump and seed pulses in the stabilized case was claimed. Following a reevaluation of the data, this was underestimated. Due to a rounding error in the calibration routine, a miscalculated calibration factor was extracted. By using a higher precision, the updated residual timing jitter amounts to 2.76 fs, or sub-3 fs. In this erratum, the calibration routine is briefly reviewed and Fig. 4, which presents the timing jitter in the stabilized and unstabilized case, is updated...
March 5, 2018: Optics Express
Reinhard Heckel
No abstract text is available yet for this article.
March 6, 2018: Nature Biotechnology
Zeljka Rupcic, Monique Rascher, Sae Kanaki, Reinhard W Köster, Marc Stadler, Kathrin Wittstein
Basidiomycetes of the genus Hericium are among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor ( NGF ) or (as established more recently) brain-derived neurotrophic factor ( BDNF ) in cell-based bioassays. The present study reports on the metabolite profiles of a Lion's Mane mushroom ( Hericium erinaceus ) strain and a strain of the rare species, Hericium flagellum (synonym H...
March 6, 2018: International Journal of Molecular Sciences
Andreas Lamkowski, Matthias Kreitlow, Jörg Radunz, Martin Willenbockel, Frank Sabath, Winfried Schuhn, Marcus Stiemer, Lars Ole Fichte, Michael Dudzinski, Sebastian Böhmelt, Reinhard Ullmann, Matthäus Majewski, Valeria Franchini, Stefan Ede, Alexis Rump, Matthias Port, Michael Abend
Radiofrequency electromagnetic fields (RF-EMF) are a basic requirement of modern wireless communication technology. Statutory thresholds of RF-EMF are established to limit relevant additional heat supply in human tissue. Nevertheless, to date, questions concerning nonthermal biological effects have yet to be fully addressed. New versions of microarrays (8 × 60K v2) provide a higher resolution of whole genome gene expression to display adaptive processes in cells after irradiation. In this ex vivo/ in vitro study, we irradiated peripheral blood cells from five donors with a continuous wave of 900 MHz RF-EMF for 0, 30, 60 and 90 min...
March 6, 2018: Radiation Research
Jinming Guo, Georg Haberfehlner, Julian Rosalie, Lei Li, María Jazmin Duarte, Gerald Kothleitner, Gerhard Dehm, Yunbin He, Reinhard Pippan, Zaoli Zhang
Oxygen contamination is a problem which inevitably occurs during severe plastic deformation of metallic powders by exposure to air. Although this contamination can change the morphology and properties of the consolidated materials, there is a lack of detailed information about the behavior of oxygen in nanocrystalline alloys. In this study, aberration-corrected high-resolution transmission electron microscopy and associated techniques are used to investigate the behavior of oxygen during in situ heating of highly strained Cu-Fe alloys...
March 5, 2018: Nature Communications
Hella Schmidt, Sebastian Vlaic, Thomas Krüger, Franziska Schmidt, Johannes Balkenhohl, Thomas Dandekar, Reinhard Guthke, Olaf Kniemeyer, Thorsten Heinekamp, Axel A Brakhage
Invasive infections by the human pathogenic fungus Aspergillus fumigatus start with the outgrowth of asexual, airborne spores (conidia) into the lung tissue of immunocompromised patients. The resident alveolar macrophages phagocytose conidia, which end up in phagolysosomes. However, A. fumigatus conidia resist phagocytic degradation to a certain degree. This is mainly attributable to the pigment 1,8-dihydroxynaphthalene (DHN) melanin located in the cell wall of conidia, which manipulates the phagolysosomal maturation and prevents their intracellular killing...
March 5, 2018: Molecular & Cellular Proteomics: MCP
Nicole Prinz, Barbara Bohn, Annamarie Kern, Deborah Püngel, Olga Pollatos, Reinhard W Holl
OBJECTIVE: For dietary assessment, mobile devices with a camera can be used as an alternative to hand-written paper records. The Nutritional Tracking Information Smartphone (Nutris-Phone) study aimed to examine relative validity and feasibility of a photo-based dietary record in everyday life. DESIGN: Parallel to the photo-based technique, a weighed record was performed. Participant satisfaction was assessed by questionnaire. A trained nutrition scientist evaluated portion sizes and nutrient content was calculated (DGExpert)...
March 6, 2018: Public Health Nutrition
Marieke Mastop, Nathalie R Reinhard, Cristiane R Zuconelli, Fenna Terwey, Theodorus W J Gadella, Jakobus van Unen, Merel J W Adjobo-Hermans, Joachim Goedhart
Förster Resonance Energy Transfer (FRET) provides a way to directly observe the activation of heterotrimeric G-proteins by G-protein coupled receptors (GPCRs). To this end, FRET based biosensors are made, employing heterotrimeric G-protein subunits tagged with fluorescent proteins. These FRET based biosensors complement existing, indirect, ways to observe GPCR activation. Here we report on the insertion of mTurquoise2 at several sites in the human Gα13 subunit, aiming to develop a FRET-based Gα13 activation biosensor...
2018: PloS One
Lydia Meder, Katharina König, Felix Dietlein, Iris Macheleidt, Alexandra Florin, Meryem S Ercanoglu, Ursula Rommerscheidt-Fuss, Mirjam Koker, Gisela Schön, Margarete Odenthal, Florian Klein, Reinhard Büttner, Johannes H Schulte, Lukas C Heukamp, Roland T Ullrich
LIN28B is a RNA-binding protein regulating predominantly let-7 microRNAs with essential functions in inflammation, wound healing, embryonic stem cells, and cancer. LIN28B expression is associated with tumor initiation, progression, resistance, and poor outcome in several solid cancers, including lung cancer. However, the functional role of LIN28B, especially in non-small cell lung adenocarcinomas, remains elusive. Here, we investigated the effects of LIN28B expression on lung tumorigenesis using LIN28B transgenic overexpression in an autochthonous KRASG12V -driven mouse model...
March 5, 2018: Oncogene
Feijian Mao, Luhua You, Martin Reinhard, YiLiang He, Karina Yew-Hoong Gin
The study investigated the occurrence and fate of seven benzophenone-type UV filters (i.e., 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2',4,4'-tetrahydroxybenzophenone (2,2',4,4'OH-BP), 2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,2'-Dihydroxy-4,4'-dimethoxybenzophenone (2,2'OH-4,4'MeO-BP), 2,2'-Dihydroxy-4-methoxybenzophenone (2,2'OH-4MeO-BP), 4-hydroxybenzophenone (4OH-BP) and 4,4'-dihyroxybenzophenone (4DHB)) in a tropical urban watershed consisting of five major tributaries that discharge into a well-managed basin...
March 5, 2018: Environmental Science & Technology
Günter Klaus, Christina Taylan, Rainer Büscher, Claus Peter Schmitt, Lars Pape, Jun Oh, Joenna Driemeyer, Matthias Galiano, Jens König, Carsten Schürfeld, Ralf Spitthöver, Juergen R Schaefer, Lutz T Weber, Andreas Heibges, Reinhard Klingel
BACKGROUND: Familial hypercholesterolemia (FH) causes premature cardiovascular disease (CVD). Lipoprotein apheresis (LA) is recommended as first-line lipid-lowering treatment (LLT) for homozygous (ho) FH. METHODS: Efficacy of multimodal LLT including lifestyle counseling, drug treatment, and LA was analyzed in 17 pediatric hoFH or compound heterozygous (c-het) FH patients, who commenced chronic LA in Germany before the age of 18. RESULTS: At time of diagnosis, mean low-density lipoprotein cholesterol (LDL-C) concentration was 19...
March 3, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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