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https://www.readbyqxmd.com/read/28722655/key-steps-in-unconventional-secretion-of-fibroblast-growth-factor-2-reconstituted-with-purified-components
#1
Julia P Steringer, Sascha Lange, Sabína Čujová, Radek Šachl, Chetan Poojari, Fabio Lolicato, Oliver Beutel, Hans-Michael Müller, Sebastian Unger, Ünal Coskun, Alf Honigmann, Ilpo Vattulainen, Martin Hof, Christian Freund, Walter Nickel
FGF2 is secreted from cells by an unconventional secretory pathway. This process is mediated by direct translocation across the plasma membrane. Here, we define the minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system. FGF2 membrane translocation is thermodynamically driven by PI(4,5)P2-induced membrane insertion of FGF2 oligomers. The latter serve as dynamic translocation intermediates of FGF2 with a subunit number in the range of 8-12 FGF2 molecules...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28722366/-large-vessel-vasculitis-pathogenesis-diagnostic-and-medical-management
#2
Alireza Sadrkhah, Jörg D Seebach, Yannick Muller
Large vessels vasculitis includes two diseases : 1) giant cell arteritis, formerly known as Horton's arteritis and 2) Takayasu arteritis. In this article, we will describe and compare the epidemiology, pathogenesis, diagnostic criteria and medical management of both vasculitis. T helper (Th) 1 and Th17 responses, genetic links and the role of viral (varicella zoster) and bacterial infection (Mycoplasma pneumoniae or Chlamydia pneumoniae) will be discussed. Classification criteria, inflammation biomarkers and progress in imaging tools will also be described...
April 5, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28721573/exposure-to-silver-nanoparticles-affects-viability-and-function-of-natural-killer-cells-mostly-via-the-release-of-ions
#3
Loretta Müller, Selina K Steiner, Laura Rodriguez-Lorenzo, Alke Petri-Fink, Barbara Rothen-Rutishauser, Philipp Latzin
Natural killer (NK) cells play a crucial role in linking innate and adaptive immune responses, especially during viral infections and tumor surveillance. They have two major effector functions: the killing of stressed/abnormal cells and the release of cytokines. Their activity is regulated via inhibitory and activating surface receptors. At the same time that the production and use of engineered nanoparticles is steadily increasing, the risk for exposure to silver nanoparticles (AgNPs) from consumer products or biomedical applications is growing...
July 18, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28721437/erk1-is-dispensable-for-mouse-pancreatic-beta-cell-function-but-is-necessary-for-glucose-induced-full-activation-of-msk1-and-creb
#4
Michele Leduc, Joy Richard, Safia Costes, Dany Muller, Annie Varrault, Vincent Compan, Julia Mathieu, Jean-François Tanti, Gilles Pagès, Jacques Pouyssegur, Gyslaine Bertrand, Stéphane Dalle, Magalie A Ravier
AIMS/HYPOTHESIS: Insufficient insulin secretion from pancreatic beta cells, which is associated with a decrease in beta cell mass, is a characteristic of type 2 diabetes. Extracellular signal-related kinase 1 and 2 (ERK1/2) inhibition in beta cells has been reported to affect insulin secretion, gene transcription and survival, although whether ERK1 and ERK2 play distinct roles is unknown. The aim of this study was to assess the individual roles of ERK1 and ERK2 in beta cells using ERK1 (also known as Mapk3)-knockout mice (Erk1 (-/-) mice) and pharmacological approaches...
July 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/28718444/tumor-host-cell-interactions-in-ovarian-cancer-pathways-to-therapy-failure
#5
REVIEW
Elke Pogge von Strandmann, Silke Reinartz, Uwe Wager, Rolf Müller
Although most ovarian cancer patients are highly responsive to chemotherapy, they frequently present with recurrent metastatic lesions that result in poor overall survival, a situation that has not changed in the last 20 years. This review discusses new insights into the regulation of ovarian cancer chemoresistance with a focus on the emerging role of immune and other host cells. Here, we summarize the complex molecular pathways that regulate the interaction between tumor and host cells, discuss the limitations of current in vitro and in vivo models for translational studies, and present perspectives for the development of innovative therapies...
February 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717423/contribution-of-neuroblastoma-derived-exosomes-to-the-production-of-pro-tumorigenic-signals-by-bone-marrow-mesenchymal-stromal-cells
#6
Rie Nakata, Hiroyuki Shimada, G Esteban Fernandez, Rob Fanter, Muller Fabbri, Jemily Malvar, Pascale Zimmermann, Yves A DeClerck
The bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines. Using three different purification methods, we then demonstrate that NB-derived exosomes were captured by MSCs and induced the production of pro-tumorigenic cytokines and chemokines, including interleukin-6 (IL-6), IL-8/CXCL8, vascular endothelial cell growth factor and monocyte-chemotactic protein-1, with exosomes prepared by size exclusion chromatography having the highest activity...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28715893/5-formyl-and-5-carboxydeoxycytidines-do-not-cause-accumulation-of-harmful-repair-intermediates-in-stem-cells
#7
René Rahimoff, Olesea Kosmatchev, Angie Kirchner, Toni Pfaffeneder, Fabio Spada, Victor Brantl, Markus Müller, Thomas Carell
5-Formyl-dC (fdC) and 5-carboxy-dC (cadC) are newly discovered bases in the mammalian genome that are sup-posed to be substrates for base excision repair (BER) in the framework of active demethylation. The bases are recognized by the monofunctional thymine DNA glycosylase (Tdg), which cleaves the glycosidic bond of the bases to give potentially harmful abasic sites (AP-sites). Due to the turnover of fdC and cadC during cell state transitions, it is an open question to what extent such harmful AP-sites may accumulate during these processes...
July 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28715160/meeting-the-who-90-target-antiretroviral-treatment-efficacy-in-poland-is-associated-with-baseline-clinical-patient-characteristics
#8
Milosz Parczewski, Ewa Siwak, Magdalena Leszczyszyn-Pynka, Iwona Cielniak, Ewa Burkacka, Piotr Pulik, Adam Witor, Karolina Muller, Ewelina Zasik, Anna Grzeszczuk, Maria Jankowska, Małgorzata Lemańska, Anita Olczak, Edyta Grąbczewska, Aleksandra Szymczak, Jacek Gąsiorowski, Bartosz Szetela, Monika Bociąga-Jasik, Paweł Skwara, Magdalena Witak-Jędra, Elżbieta Jabłonowska, Kamila Wójcik-Cichy, Juliusz Kamerys, Małgorzata Janczarek, Dagny Krankowska, Tomasz Mikuła, Katarzyna Kozieł, Dariusz Bielec, Justyna Stempkowska, Aleksandra Kocbach, Wiesława Błudzin, Andrzej Horban
INTRODUCTION: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. M: ethods Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres...
July 17, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28714017/targeting-vegfr-and-fgfr-in-head-and-neck-squamous-cell-carcinoma-in-vitro
#9
Roman C Brands, Luise M Knierim, Francesco De Donno, Valentin Steinacker, Stefan Hartmann, Axel Seher, Alexander C Kübler, Urs D A Müller-Richter
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease characterized by a tumor microenvironment (TME) that overexpresses vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which can lead to neovascularization, tumor growth and metastasis. Therapeutic strategies inhibiting these signaling pathways might lead to innovative HNSCC treatments. Five HNSCC cell lines were characterized based on VEGFR1-3 and FGFR1-4 expression by sqRT-PCR and treated with three different tyrosine kinase inhibitors (TKIs) (nintedanib, dovitinib and pazopanib), all of which are effective against VEGFR and FGFR family members...
July 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713655/differential-effect-of-platelet-endothelial-cell-adhesion-molecule-1-pecam-1-on-leukocyte-infiltration-during-contact-hypersensitivity-responses
#10
Merideth Early, William G Schroeder, Ranajana Unnithan, John M Gilchrist, William A Muller, Alan Schenkel
BACKGROUND: 2'-4' Dinitrofluorobenzene (DNFB) induced contact hypersensitivity is an established model of contact sensitivity and leukocyte migration. Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) deficient mice were used to examine the role of PECAM-1 in the migration capacity of several different leukocyte populations after primary and secondary application. RESULTS: γδ T lymphocytes, granulocytes, and Natural Killer cells were most affected by PECAM-1 deficiency at the primary site of application...
2017: PeerJ
https://www.readbyqxmd.com/read/28710541/injury-induced-purinergic-signalling-molecules-upregulate-pluripotency-gene-expression-and-mitotic-activity-of-progenitor-cells-in-the-zebrafish-retina
#11
Matías P Medrano, Claudio A Bejarano, Ariadna G Battista, Graciela D Venera, Ramón O Bernabeu, Maria Paula Faillace
Damage in fish activates retina repair that restores sight. The purinergic signalling system serves multiple homeostatic functions and has been implicated in cell cycle control of progenitor cells in the developing retina. We examined whether changes in the expression of purinergic molecules were instrumental in the proliferative phase after injury of adult zebrafish retinas with ouabain. P2RY1 messenger RNA (mRNA) increased early after injury and showed maximal levels at the time of peak progenitor cell proliferation...
July 14, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28710263/enzymatic-mechanism-for-arabinan-degradation-and-transport-in-the-thermophilic-bacterium-caldanaerobius-polysaccharolyticus
#12
Daniel Wefers, Jia Dong, Ahmed M Abdel-Hamid, Hans Müller Paul, Gabriel V Pereira, Yejun Han, Dylan Dodd, Ramiya Baskaran, Beth Mayer, Roderick I Mackie, Isaac Cann
The plant cell wall polysaccharide arabinan is an important supply of arabinose, and unraveling arabinan degrading strategies by microbes is important for understanding its use as a source of energy. Here, we explored the arabinan degrading enzymes in the thermophilic bacterium Caldanaerobius polysaccharolyticus and identified a gene cluster encoding two glycoside hydrolase (GH) family 51 α-L-arabinofuranosidases (CpAbf51A, CpAbf51B), a GH43 endo-arabinanase (CpAbn43A), a GH27 β-L-arabinopyranosidase (CpAbp27A), and two GH127 β-L-arabinofuranosidases (CpAbf127A, CpAbf127B)...
July 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28709891/neuroprotective-effects-of-methyl-3-4-dihydroxybenzoate-in-a-mouse-model-of-retinitis-pigmentosa
#13
Jia Zhang, Di Xu, Huan Ouyang, Songhui Hu, Ang Li, Huanmin Luo, Ying Xu
Retinitis pigmentosa is a photoreceptor-degenerative disease that is currently untreatable and eventually causes blindness. Methyl 3,4 dihydroxybenzoate (MDHB) is a small molecule that exerts neuroprotective effect in vitro. The present study tests whether MDHB protects the retina of rd10 mice, a model of retinitis pigmentosa. MDHB or equal volume of vehicle was intraperitoneally injected in rd10 mice daily from postnatal day 12 (P12) to P26. Retinal morphology was evaluated by immunostaining, and retinal function by electroretinogram (ERG) and by visual behavior...
July 11, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28709426/xue-fu-zhu-yu-decoction-protects-rats-against-retinal-ischemia-by-downregulation-of-hif-1%C3%AE-and-vegf-via-inhibition-of-rbp2-and-pkm2
#14
Shu-Qiu Tan, Xue Geng, Jorn-Hon Liu, Wynn Hwai-Tzong Pan, Li-Xiang Wang, Hui-Kang Liu, Lei Hu, Hsiao-Ming Chao
BACKGROUND: Retinal ischemia-related eye diseases result in visual dysfunction. This study investigates the protective effects and mechanisms of Xue-Fu-Zhu-Yu decoction (XFZYD) with respect to retinal ischemia. METHODS: Retinal ischemia (I) was induced in Wistar rats by a high intraocular pressure (HIOP) of 120 mmHg for 1 h, which was followed by reperfusion of the ischemic eye; the fellow untreated eye acted as a control. Electroretinogram (ERG), biochemistry and histopathology investigations were performed...
July 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28708873/impact-of-early-cart-on-hiv-blood-and-semen-compartments-at-the-time-of-primary-infection
#15
Antoine Chéret, Christine Durier, Adeline Mélard, Mickaël Ploquin, Julia Heitzmann, Camille Lécuroux, Véronique Avettand-Fenoël, Ludivine David, Gilles Pialoux, Jean-Marie Chennebault, Michaela Müller-Trutwin, Cécile Goujard, Christine Rouzioux, Laurence Meyer
BACKGROUND: HIV-infected cells in semen facilitate viral transmission. We studied the establishment of HIV reservoirs in semen and blood during PHI, along with systemic immune activation and the impact of early cART. METHODS: Patients in the ANRS-147-OPTIPRIM trial received two years of early cART. Nineteen patients of the trial were analyzed, out of which 8 had acute PHI (WB ≤1 Ab). We quantified total cell-associated (ca) HIV-DNA in blood and semen and HIV-RNA in blood and semen plasma samples, collected during PHI and at 24 months of treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28708400/contribution-of-mate1-to-renal-secretion-of-the-nmda-receptor-antagonist-memantine
#16
Fabian Müller, Dietmar Weitz, Volker Derdau, Martin Sandvoss, Katharina Mertsch, Jörg König, Martin F Fromm
The weak base memantine is actively secreted into urine, however the underlying mechanisms are insufficiently understood. Potential candidates involved in memantine renal secretion are organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATE1, MATE2-K). The aim of this in vitro study was the examination of the interaction of memantine with OCT2 and MATEs. Memantine transporter inhibition and transport were examined in HEK cells expressing human OCT2, MATE1, or MATE2-K. Monolayers of single- (MDCK-OCT2, MDCK-MATE1) and double-transfected MDCK cells (MDCK-OCT2-MATE1) were used for studies on vectorial, basal to apical memantine transport...
July 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28706966/data-on-the-fate-of-macs%C3%A2-microbeads-intramyocardially-co-injected-with-stem-cell-products
#17
Paula Müller, Ralf Gaebel, Heiko Lemcke, Gustav Steinhoff, Robert David
The data presented in this article are related to the research article "Intramyocardial Fate and Effect of Iron Nanoparticles co-injected with MACS® purified Stem Cell Products" (Müller et al., 2017) [1]. This article complements the cellular localization of superparamagnetic iron dextran particles (MACS® MicroBeads) used for magnetic activated cell sorting (MACS®). Data evaluate the time-dependent detachment of these nanoparticles from CD133(+) haematopoietic stem cells (HSCs) and CD271(+) mesenchymal stem cells (MSCs)...
August 2017: Data in Brief
https://www.readbyqxmd.com/read/28706306/ligand-induced-type-ii-interleukin-4-receptor-dimers-are-sustained-by-rapid-re-association-within-plasma-membrane-microcompartments
#18
David Richter, Ignacio Moraga, Hauke Winkelmann, Oliver Birkholz, Stephan Wilmes, Markos Schulte, Michael Kraich, Hella Kenneweg, Oliver Beutel, Philipp Selenschik, Dirk Paterok, Martynas Gavutis, Thomas Schmidt, K Christopher Garcia, Thomas D Müller, Jacob Piehler
The spatiotemporal organization of cytokine receptors in the plasma membrane is still debated with models ranging from ligand-independent receptor pre-dimerization to ligand-induced receptor dimerization occurring only after receptor uptake into endosomes. Here, we explore the molecular and cellular determinants governing the assembly of the type II interleukin-4 receptor, taking advantage of various agonists binding the receptor subunits with different affinities and rate constants. Quantitative kinetic studies using artificial membranes confirm that receptor dimerization is governed by the two-dimensional ligand-receptor interactions and identify a critical role of the transmembrane domain in receptor dimerization...
July 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28705258/fate-bias-during-neural-regeneration-adjusts-dynamically-without-recapitulating-developmental-fate-progression
#19
Jeremy Ng Chi Kei, Peter David Currie, Patricia Regina Jusuf
BACKGROUND: Regeneration of neurons in the central nervous system is poor in humans. In other vertebrates neural regeneration does occur efficiently and involves reactivation of developmental processes. Within the neural retina of zebrafish, Müller glia are the main stem cell source and are capable of generating progenitors to replace lost neurons after injury. However, it remains largely unknown to what extent Müller glia and neuron differentiation mirror development. METHODS: Following neural ablation in the zebrafish retina, dividing cells were tracked using a prolonged labelling technique...
July 13, 2017: Neural Development
https://www.readbyqxmd.com/read/28704452/influence-of-lung-ct-changes-in-chronic-obstructive-pulmonary-disease-copd-on-the-human-lung-microbiome
#20
Marion Engel, David Endesfelder, Brigitte Schloter-Hai, Susanne Kublik, Michael S Granitsiotis, Piera Boschetto, Mariarita Stendardo, Imre Barta, Balazs Dome, Jean-François Deleuze, Anne Boland, Joachim Müller-Quernheim, Antje Prasse, Tobias Welte, Jens Hohlfeld, Deepak Subramanian, David Parr, Ivo Glynne Gut, Timm Greulich, Andreas Rembert Koczulla, Adam Nowinski, Dorota Gorecka, Dave Singh, Sumit Gupta, Christopher E Brightling, Harald Hoffmann, Marion Frankenberger, Thomas P Hofer, Dorothe Burggraf, Marion Heiss-Neumann, Loems Ziegler-Heitbrock, Michael Schloter, Wolfgang Zu Castell
BACKGROUND: Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited. METHODS: Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons...
2017: PloS One
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