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Yaxin An, Manja Reimann, Jimmy Masjkur, Katharina Langton, Mirko Peitzsch, Timo Deutschbein, Martin Fassnacht, Natalie Rogowski-Lehmann, Felix Beuschlein, Stephanie Fliedner, Anthony Stell, Aleksander Prejbisz, Andrzej Januszewicz, Jacques Lenders, Stefan R Bornstein, Graeme Eisenhofer
BACKGROUND: Obesity-associated activation of sympathetic nervous outflow is well documented, whereas involvement of dysregulated adrenomedullary hormonal function in obesity is less clear. This study assessed relationships of sympathoadrenal function with indices of obesity and influences of circulating catecholamines on body mass. METHODS: Anthropometric and clinical data along with plasma and 24-h urine samples were collected from 590 volunteers and 1368 patients tested for phaeochromocytoma and paraganglioma (PPGL), among whom tumours were diagnosed in 210 individuals...
March 3, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Anna Stelling, Hind Hashwah, Katrin Bertram, Markus G Manz, Alexandar Tzankov, Anne Müller
The sphingosine-1-phosphate receptor S1PR2 and its downstream signaling pathway is commonly silenced in diffuse large B-cell lymphoma (DLBCL), either by mutational inactivation or through negative regulation by the oncogenic transcription factor FOXP1. In this study, we have examined the upstream regulators of S1PR2 expression and have newly identified the TGF-β/TGF-βR2/SMAD1 axis as critically involved in S1PR2 transcriptional activation. Phosphorylated SMAD1 directly binds to regulatory elements in the S1PR2 locus as assessed by chromatin immunoprecipitation, and the CRISPR-mediated genomic editing of S1PR2 , SMAD1 or TGFBR2 in DLBCL cell lines renders cells unresponsive to TGF-β-induced apoptosis...
April 3, 2018: Blood
Lukas Andreas Widmer, Jörg Stelling
The impact of intracellular spatial organization beyond classical compartments on processes such as cell signaling is increasingly recognized. A quantitative, mechanistic understanding of cellular systems therefore needs to account for different scales in at least three coordinates: time, molecular abundances, and space. Mechanistic mathematical models may span all these scales, but corresponding multi-scale models need to resolve mechanistic details on small scales while maintaining computational tractability for larger ones...
February 24, 2018: Current Opinion in Biotechnology
Mary Prunicki, Laurel Stell, Deendayal Dinakarpandian, Mariangels de Planell-Saguer, Richard W Lucas, S Katharine Hammond, John R Balmes, Xiaoying Zhou, Tara Paglino, Chiara Sabatti, Rachel L Miller, Kari C Nadeau
Background: DNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation ( Foxp3 and IL10 ) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites...
2018: Clinical Epigenetics
D M Waldner, N C Giraldo Sierra, S Bonfield, L Nguyen, I S Dimopoulos, Y Sauvé, W K Stell, N T Bech-Hansen
Congenital stationary night blindness 2A (CSNB2A) is an X-linked retinal disorder, characterized by phenotypically variable signs and symptoms of impaired vision. CSNB2A is due to mutations in CACNA1F, which codes for the pore-forming α1F subunit of a L-type voltage-gated calcium channel, Cav 1.4. Mouse models of CSNB2A, used for characterizing the effects of various Cacna1f mutations, have revealed greater severity of defects than in human CSNB2A. Specifically, Cacna1f-knockout mice show an apparent lack of visual function, gradual retinal degeneration, and disruption of photoreceptor synaptic terminals...
January 1, 2018: Channels
Helge Hass, Kristina Masson, Sibylle Wohlgemuth, Violette Paragas, John E Allen, Mark Sevecka, Emily Pace, Jens Timmer, Joerg Stelling, Gavin MacBeath, Birgit Schoeberl, Andreas Raue
Targeted therapies have shown significant patient benefit in about 5-10% of solid tumors that are addicted to a single oncogene. Here, we explore the idea of ligand addiction as a driver of tumor growth. High ligand levels in tumors have been shown to be associated with impaired patient survival, but targeted therapies have not yet shown great benefit in unselected patient populations. Using an approach of applying Bagged Decision Trees (BDT) to high-dimensional signaling features derived from a computational model, we can predict ligand dependent proliferation across a set of 58 cell lines...
2017: NPJ Systems Biology and Applications
Hind Hashwah, Corina A Schmid, Sabrina Kasser, Katrin Bertram, Anna Stelling, Markus G Manz, Anne Müller
The genes encoding the histone acetyl-transferases (HATs) CREB binding protein (CREBBP) and EP300 are recurrently mutated in the activated B cell-like and germinal center (GC) B cell-like subtypes of diffuse large B cell lymphoma (DLBCL). Here, we introduced a patient mutation into a human DLBCL cell line using CRISPR and deleted Crebbp and Ep300 in the GC B cell compartment of mice. CREBBP-mutant DLBCL clones exhibited reduced histone H3 acetylation, expressed significantly less MHCII, and grew faster than wild-type clones in s...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
Saeed Mohammadi, Mohsen Nikbakht, Seyed Mehdi Sajjadi, Fariba Rad, Bahram Chahardouli, Javid Sabour Takanlu, Shahrbano Rostami, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
A predominant challenge in developing curative leukemia therapy is interactions of leukemic cells with the bone marrow stromal microenvironment. We aimed to investigate the role of stromal cells, such as bone marrow mesenchymal stromal cells (BMSCs) and osteoblasts (OBs), in curcumin (CUR) and daunorubicin (DNR) induced apoptosis of acute myeloid leukemia (AML) cells. We used KG1 and U937 as leukemia cell line models and treated them with CUR and DNR. The cells were then co-cultured with BMSCs or a combination of BMSCs and OBs as feeders...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
Irene Otero-Muras, Pencho Yordanov, Joerg Stelling
Bistability has important implications in signaling pathways, since it indicates a potential cell decision between alternative outcomes. We present two approaches developed in the framework of the Chemical Reaction Network Theory for easy and efficient search of multiple steady state behavior in signaling networks (both with and without mass conservation), and apply them to search for sources of bistability at different levels of the interferon signaling pathway. Different type I interferon subtypes and/or doses are known to elicit differential bioactivities (ranging from antiviral, antiproliferative to immunomodulatory activities)...
April 2017: PLoS Computational Biology
Vitalii V Mutsenko, Oleksandr Gryshkov, Lothar Lauterboeck, Olena Rogulska, Dmitriy N Tarusin, Vasilii V Bazhenov, Kathleen Schütz, Sophie Brüggemeier, Elke Gossla, Ashwini R Akkineni, Heike Meißner, Anja Lode, Stephan Meschke, Jane Fromont, Allison L Stelling, Konstantin R Tabachnik, Michael Gelinsky, Sergey Nikulin, Sergey Rodin, Alexander G Tonevitsky, Alexander Y Petrenko, Birgit Glasmacher, Peter J Schupp, Hermann Ehrlich
The extraordinary biocompatibility and mechanical properties of chitinous scaffolds from marine sponges endows these structures with unique properties that render them ideal for diverse biomedical applications. In the present work, a technological route to produce "ready-to-use" tissue-engineered products based on poriferan chitin is comprehensively investigated for the first time. Three key stages included isolation of scaffolds from the marine demosponge Ianthella basta, confirmation of their biocompatibility with human mesenchymal stromal cells, and cryopreservation of the tissue-like structures grown within these scaffolds using a slow cooling protocol...
March 30, 2017: International Journal of Biological Macromolecules
Vitalii V Mutsenko, Vasilii V Bazhenov, Olena Rogulska, Dmitriy N Tarusin, Kathleen Schütz, Sophie Brüggemeier, Elke Gossla, Ashwini R Akkineni, Heike Meißner, Anja Lode, Stephan Meschke, Andre Ehrlich, Slavica Petović, Rajko Martinović, Mirko Djurović, Allison L Stelling, Sergey Nikulin, Sergey Rodin, Alexander Tonevitsky, Michael Gelinsky, Alexander Y Petrenko, Birgit Glasmacher, Hermann Ehrlich
The recently discovered chitin-based scaffolds derived from poriferans have the necessary prosperities for potential use in tissue engineering. Among the various demosponges of the Verongida order, Aplysina aerophoba is an attractive target for more in-depth investigations, as it is a renewable source of unique 3D microporous chitinous scaffolds. We found these chitinous scaffolds were cytocompatible and supported attachment, growth and proliferation of human mesenchymal stromal cells (hMSCs) in vitro. Cultivation of hMSCs on the scaffolds for 7days resulted in a two-fold increase in their metabolic activity, indicating increased cell numbers...
March 25, 2017: International Journal of Biological Macromolecules
Christian Stelling, Chetan R Singh, Matthias Karg, Tobias A F König, Mukundan Thelakkat, Markus Retsch
In this contribution, the optical losses and gains attributed to periodic nanohole array electrodes in polymer solar cells are systematically studied. For this, thin gold nanomeshes with hexagonally ordered holes and periodicities (P) ranging from 202 nm to 2560 nm are prepared by colloidal lithography. In combination with two different active layer materials (P3HT:PC61BM and PTB7:PC71BM), the optical properties are correlated with the power conversion efficiency (PCE) of the solar cells. A cavity mode is identified at the absorption edge of the active layer material...
February 15, 2017: Scientific Reports
Rafaela C Sartore, Simone C Cardoso, Yury V M Lages, Julia M Paraguassu, Mariana P Stelling, Rodrigo F Madeiro da Costa, Marilia Z Guimaraes, Carlos A Pérez, Stevens K Rehen
Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development in vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain...
2017: PeerJ
Stell Patadji, Zaibo Li, Dinesh Pradhan, Chengquan Zhao
BACKGROUND: The role of high-risk human papillomavirus (hrHPV) testing in women with various types of atypical glandular cells (AGC) on Papanicolaou (Pap) test is undetermined. METHODS: Herein, the authors retrospectively searched their pathology database for cases of AGC with concurrent hrHPV testing and histological follow-up results within 1 year between January 2008 and December 2013. RESULTS: Among 3709 AGC cases occurring during the study period, 2287 had concurrent Hybrid Capture 2 HPV testing results...
March 2017: Cancer Cytopathology
Jorge E Ramirez, Brandon M Stell
The brain's control of movement is thought to involve coordinated activity between cerebellar Purkinje cells. The results reported here demonstrate that somatic Ca2+ imaging is a faithful reporter of Na+ -dependent "simple spike" pauses and enables us to optically record changes in firing rates in populations of Purkinje cells in brain slices and in vivo. This simultaneous calcium imaging of populations of Purkinje cells reveals a striking spatial organization of pauses in Purkinje cell activity between neighboring cells...
December 20, 2016: Cell Reports
Mingqi Xie, Haifeng Ye, Hui Wang, Ghislaine Charpin-El Hamri, Claude Lormeau, Pratik Saxena, Jörg Stelling, Martin Fussenegger
Chronically deregulated blood-glucose concentrations in diabetes mellitus result from a loss of pancreatic insulin-producing β cells (type 1 diabetes, T1D) or from impaired insulin sensitivity of body cells and glucose-stimulated insulin release (type 2 diabetes, T2D). Here, we show that therapeutically applicable β-cell-mimetic designer cells can be established by minimal engineering of human cells. We achieved glucose responsiveness by a synthetic circuit that couples glycolysis-mediated calcium entry to an excitation-transcription system controlling therapeutic transgene expression...
December 9, 2016: Science
Edris Hoseinzadeh, Pouran Makhdoumi, Parisa Taha, Hooshyar Hossini, John Stelling, Mohammad Amjad Kamal, Ghulam Md Ashraf
Nanotechnology is a scientific and engineering technology conducted at the nano-scale, such as in the fields of compound fabric manufacturing, food processing, agricultural processing, and engineering, as well as in medical and medicinal applications. In recent decade, nanomaterial applications for antimicrobial works have of prime interest of by many researchers. Available reports show that some of the metal oxide nanoparticles (NPs) including Al2O3, TiO2, ZnO, CuO, Co3O4, In2O3, MgO, SiO2, ZrO2, Cr2O3, Ni2O3, Mn2O3, CoO, and Nickel oxide have toxicity toward several microorganisms and they could successfully kill numerous bacteria...
2017: Current Drug Metabolism
Ross P Wilkie, Andrew R Neal, Craig A Johnston, Nicholas Voute, Christopher S Lancefield, Matthew D Stell, Federico Medda, Edward F Makiyi, Emma M Turner, O Stephen Ojo, Alexandra M Z Slawin, Tomas Lebl, Peter Mullen, David J Harrison, Chris M Ireland, Nicholas J Westwood
The synthesis of dehaloperophoramidine, a non-halogenated derivative of the marine natural product perophoramidine, and its biological activity towards HCT116, HT29 and LoVo colorectal carcinoma cells is reported. A [3,3]-Claisen rearrangement and an epoxide opening/allylsilylation reaction installed the contiguous all-carbon quaternary stereocentres with the required relative stereochemistry.
September 14, 2016: Chemical Communications: Chem Comm
Stell Patadji, Joshua Pantanowitz, Natalie M Perlov, Sara E Monaco
INTRODUCTION: Arborizing stromal meshwork fragments (ASMFs) have been proposed as a useful clue to differentiate mucin associated with mucinous adenocarcinoma from contaminating mucus during endobronchial ultrasound-guided transbronchial needle aspiration. Our aim was to retrospectively review cytology cases with mucinous material to determine the utility of ASMFs in diagnosing mucinous tumors. MATERIAL AND METHODS: Diff-Quik stained smears from archival cytology cases (N = 40) were reviewed, including adenocarcinomas with mucinous features, cystic mucinous neoplasms, and control cases with mucin contamination...
October 2016: Diagnostic Cytopathology
Malte B Monin, Petra Krause, Robin Stelling, Derya Bocuk, Sabine Niebert, Florian Klemm, Tobias Pukrop, Sarah Koenig
BACKGROUND: Wnt/β-catenin signaling is known to play an important role in colorectal cancer (CRC). Niclosamide, a salicylamide derivative used in the treatment of tapeworm infections, targets the Wnt/β-catenin pathway. The objective of this study was to investigate niclosamide as a therapeutic agent against CRC. METHODS: The antiproliferative effects of 1, 3, 10, and 50 μM concentrations of niclosamide on human (SW480 and SW620) and rodent (CC531) CRC cell lines were determined by MTS assay and direct cell count...
June 1, 2016: Journal of Surgical Research
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