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Alexander Meissner

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https://www.readbyqxmd.com/read/30195438/aligning-single-cell-developmental-and-reprogramming-trajectories-identifies-molecular-determinants-of-myogenic-reprogramming-outcome
#1
Davide Cacchiarelli, Xiaojie Qiu, Sanjay Srivatsan, Anna Manfredi, Michael Ziller, Eliah Overbey, Antonio Grimaldi, Jonna Grimsby, Prapti Pokharel, Kenneth J Livak, Shuqiang Li, Alexander Meissner, Tarjei S Mikkelsen, John L Rinn, Cole Trapnell
Cellular reprogramming through manipulation of defined factors holds great promise for large-scale production of cell types needed for use in therapy and for revealing principles of gene regulation. However, most reprogramming systems are inefficient, converting only a fraction of cells to the desired state. Here, we analyze MYOD-mediated reprogramming of human fibroblasts to myotubes, a well-characterized model system for direct conversion by defined factors, at pseudotemporal resolution using single-cell RNA-seq...
September 26, 2018: Cell Systems
https://www.readbyqxmd.com/read/30133046/chemical-exchange-saturation-transfer-cest-signal-intensity-at-7t-mri-of-who-iv%C3%A2-gliomas-is-dependent-on-the-anatomic-location
#2
Constantin Dreher, Johanna Oberhollenzer, Jan-Eric Meissner, Johannes Windschuh, Patrick Schuenke, Sebastian Regnery, Felix Sahm, Sebastian Bickelhaupt, Martin Bendszus, Wolfgang Wick, Andreas Unterberg, Moritz Zaiss, Peter Bachert, Mark E Ladd, Heinz-Peter Schlemmer, Alexander Radbruch, Daniel Paech
BACKGROUND: Chemical exchange saturation transfer (CEST) is a novel MRI technique applied to brain tumor patients. PURPOSE: To investigate the anatomic location dependence of CEST MRI obtained at 7T and histopathological/molecular parameters in WHO IV° glioma patients. STUDY TYPE: Analytic prospective study. POPULATION: Twenty-one patients with newly diagnosed WHO IV° gliomas were studied prior to surgery; 11 healthy volunteers were investigated...
August 22, 2018: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/30127506/reduced-mek-inhibition-preserves-genomic-stability-in-naive-human-embryonic-stem-cells
#3
Bruno Di Stefano, Mai Ueda, Shan Sabri, Justin Brumbaugh, Aaron J Huebner, Anna Sahakyan, Kendell Clement, Katie J Clowers, Alison R Erickson, Keiko Shioda, Steven P Gygi, Hongcang Gu, Toshi Shioda, Alexander Meissner, Yasuhiro Takashima, Kathrin Plath, Konrad Hochedlinger
Human embryonic stem cells (hESCs) can be captured in a primed state in which they resemble the postimplantation epiblast, or in a naive state where they resemble the preimplantation epiblast. Naive-cell-specific culture conditions allow the study of preimplantation development ex vivo but reportedly lead to chromosomal abnormalities, which compromises their utility in research and potential therapeutic applications. Although MEK inhibition is essential for the naive state, here we show that reduced MEK inhibition facilitated the establishment and maintenance of naive hESCs that retained naive-cell-specific features, including global DNA hypomethylation, HERVK expression, and two active X chromosomes...
September 2018: Nature Methods
https://www.readbyqxmd.com/read/30102379/chromatin-dependent-allosteric-regulation-of-dnmt3a-activity-by-mecp2
#4
Arumugam Rajavelu, Cristiana Lungu, Max Emperle, Michael Dukatz, Alexander Bröhm, Julian Broche, Ines Hanelt, Edris Parsa, Sarah Schiffers, Rahul Karnik, Alexander Meissner, Thomas Carell, Philipp Rathert, Renata Z Jurkowska, Albert Jeltsch
Despite their central importance in mammalian development, the mechanisms that regulate the DNA methylation machinery and thereby the generation of genomic methylation patterns are still poorly understood. Here, we identify the 5mC-binding protein MeCP2 as a direct and strong interactor of DNA methyltransferase 3 (DNMT3) proteins. We mapped the interaction interface to the transcriptional repression domain of MeCP2 and the ADD domain of DNMT3A and find that binding of MeCP2 strongly inhibits the activity of DNMT3A in vitro...
September 28, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/30055373/scaling-properties-of-pain-intensity-ratings-in-paediatric-populations-using-the-faces-pain-scale-revised-secondary-analyses-of-published-data-based-on-the-item-response-theory
#5
Alexander Avian, Brigitte Messerer, Andreas Frey, Winfried Meissner, Annelie Weinberg, William Ravekes, Andrea Berghold
BACKGROUND: The Faces Pain Scale-revised (FPS-r) has been developed as an interval scale. For other pain measurement instruments, several studies found evidence for and against an interval level of measurement. OBJECTIVES: The primary aim of the current study was to evaluate the scale properties of the FPS-r using an item response theory approach. DESIGN: Secondary analysis of published data. SETTING: Three studies; Study 1 and study 2: One university hospital; Study 3: international pain registry...
July 17, 2018: International Journal of Nursing Studies
https://www.readbyqxmd.com/read/30027117/domain-meissner-state-and-spontaneous-vortex-antivortex-generation-in-the-ferromagnetic-superconductor-eufe-2-as-0-79-p-0-21-2
#6
Vasily S Stolyarov, Ivan S Veshchunov, Sergey Yu Grebenchuk, Denis S Baranov, Igor A Golovchanskiy, Andrey G Shishkin, Nan Zhou, Zhixiang Shi, Xiaofeng Xu, Sunseng Pyon, Yue Sun, Wenhe Jiao, Guang-Han Cao, Lev Ya Vinnikov, Alexander A Golubov, Tsuyoshi Tamegai, Alexander I Buzdin, Dimitri Roditchev
The interplay between superconductivity and magnetism is one of the oldest enigmas in physics. Usually, the strong exchange field of ferromagnet suppresses singlet superconductivity via the paramagnetic effect. In EuFe2 (As0.79 P0.21 )2 , a material that becomes not only superconducting at 24.2 K but also ferromagnetic below 19 K, the coexistence of the two antagonistic phenomena becomes possible because of the unusually weak exchange field produced by the Eu subsystem. We demonstrate experimentally and theoretically that when the ferromagnetism adds to superconductivity, the Meissner state becomes spontaneously inhomogeneous, characterized by a nanometer-scale striped domain structure...
July 2018: Science Advances
https://www.readbyqxmd.com/read/30017590/prospective-isolation-of-poised-ipsc-intermediates-reveals-principles-of-cellular-reprogramming
#7
Benjamin A Schwarz, Murat Cetinbas, Kendell Clement, Ryan M Walsh, Sihem Cheloufi, Hongcang Gu, Jan Langkabel, Akihide Kamiya, Hubert Schorle, Alexander Meissner, Ruslan I Sadreyev, Konrad Hochedlinger
Cellular reprogramming converts differentiated cells into induced pluripotent stem cells (iPSCs). However, this process is typically very inefficient, complicating mechanistic studies. We identified and molecularly characterized rare, early intermediates poised to reprogram with up to 95% efficiency, without perturbing additional genes or pathways, during iPSC generation from mouse embryonic fibroblasts. Analysis of these cells uncovered transcription factors (e.g., Tfap2c and Bex2) that are important for reprogramming but dispensable for pluripotency maintenance...
August 2, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29983895/chemical-exchange-saturation-transfer-mri-serves-as-predictor-of-early-progression-in-glioblastoma-patients
#8
Sebastian Regnery, Sebastian Adeberg, Constantin Dreher, Johanna Oberhollenzer, Jan-Eric Meissner, Steffen Goerke, Johannes Windschuh, Katerina Deike-Hofmann, Sebastian Bickelhaupt, Moritz Zaiss, Alexander Radbruch, Martin Bendszus, Wolfgang Wick, Andreas Unterberg, Stefan Rieken, Jürgen Debus, Peter Bachert, Mark Ladd, Heinz-Peter Schlemmer, Daniel Paech
Purpose: To prospectively investigate chemical exchange saturation transfer (CEST) MRI in glioblastoma patients as predictor of early tumor progression after first-line treatment. Experimental Design: Twenty previously untreated glioblastoma patients underwent CEST MRI employing a 7T whole-body scanner. Nuclear Overhauser effect (NOE) as well as amide proton transfer (APT) CEST signals were isolated using Lorentzian difference (LD) analysis and relaxation compensated by the apparent exchange-dependent relaxation rate (AREX) evaluation...
June 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29804889/an-intermediate-pluripotent-state-controlled-by-micrornas-is-required-for-the-naive-to-primed-stem-cell-transition
#9
Peng Du, Mehdi Pirouz, Jiho Choi, Aaron J Huebner, Kendell Clement, Alexander Meissner, Konrad Hochedlinger, Richard I Gregory
The embryonic stem cell (ESC) transition from naive to primed pluripotency is marked by major changes in cellular properties and developmental potential. ISY1 regulates microRNA (miRNA) biogenesis, yet its role and relevance to ESC biology remain unknown. Here, we find that highly dynamic ISY1 expression during the naive-to-primed ESC transition defines a specific phase of "poised" pluripotency characterized by distinct miRNA and mRNA transcriptomes and widespread poised cell contribution to mouse chimeras...
June 1, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29758587/regional-vs-general-anesthesia-for-total-knee-and-hip-replacement-an-analysis-of-postoperative-pain-perception-from-the-international-pain-out-registry
#10
Katharina Donauer, Hagen Bomberg, Stefan Wagenpfeil, Thomas Volk, Winfried Meissner, Alexander Wolf
BACKGROUND: Total hip and knee replacements are common surgeries, and an optimal pain treatment is essential for early rehabilitation. Since data from randomized controlled trials on the use of regional anesthesia in joint replacements of the lower extremities are conflicting, we analyzed the international PAIN OUT registry for comparison of regional anesthesia vs. general anesthesia regarding pain and morphine consumption on the first postoperative day. METHODS: International Classification of Diseases-9 (ICD-9) codes were used to identify 2,346 cases of knee arthroplasty and 2,315 cases of hip arthroplasty between 2010 and 2016 from the PAIN OUT registry...
May 14, 2018: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/29735753/metabolism-and-disposition-of-siponimod-a-novel-selective-s1p-1-s1p-5-agonist-in-healthy-volunteers-and-in-vitro-identification-of-human-cytochrome-p450-enzymes-involved-in-its-oxidative-metabolism
#11
Ulrike Glaenzel, Yi Jin, Robert Nufer, Wenkui Li, Kirsten Schroer, Sylvie Adam-Stitah, Sjoerd Peter van Marle, Eric Legangneux, Hubert Borell, Alexander D James, Axel Meissner, Gian Camenisch, Anne Gardin
Siponimod, a next-generation selective sphingosine-1-phosphate receptor modulator, is currently being investigated for the treatment of secondary progressive multiple sclerosis. We investigated the absorption, distribution, metabolism, and excretion (ADME) of a single 10-mg oral dose of [14 C]siponimod in four healthy men. Mass balance, blood and plasma radioactivity, and plasma siponimod concentrations were measured. Metabolite profiles were determined in plasma, urine, and feces. Metabolite structures were elucidated using mass spectrometry and comparison with reference compounds...
July 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29733378/assessing-the-predictability-of-idh-mutation-and-mgmt-methylation-status-in-glioma-patients-using-relaxation-compensated-multi-pool-cest-mri-at-7-0-tesla
#12
Daniel Paech, Johannes Windschuh, Johanna Oberhollenzer, Constantin Dreher, Felix Sahm, Jan-Eric Meissner, Steffen Goerke, Patrick Schuenke, Moritz Zaiss, Sebastian Regnery, Sebastian Bickelhaupt, Philipp Bäumer, Martin Bendszus, Wolfgang Wick, Andreas Unterberg, Peter Bachert, Mark Edward Ladd, Heinz-Peter Schlemmer, Alexander Radbruch
Background: Early identification of prognostic superior characteristics in glioma patients such as Isocitrate dehydrogenase(IDH)-mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promotor methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH-mutation status, MGMT promotor methylation, and differentiation of lower versus higher grade glioma (LGG vs. HGG) in newly-diagnosed patients employing relaxation-compensated multi-pool Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) at 7...
May 4, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29681539/x-chromosome-dosage-influences-dna-methylation-dynamics-during-reprogramming-to-mouse-ipscs
#13
Vincent Pasque, Rahul Karnik, Constantinos Chronis, Paula Petrella, Justin Langerman, Giancarlo Bonora, Juan Song, Lotte Vanheer, Anupama Sadhu Dimashkie, Alexander Meissner, Kathrin Plath
A dramatic difference in global DNA methylation between male and female cells characterizes mouse embryonic stem cells (ESCs), unlike somatic cells. We analyzed DNA methylation changes during reprogramming of male and female somatic cells and in resulting induced pluripotent stem cells (iPSCs). At an intermediate reprogramming stage, somatic and pluripotency enhancers are targeted for partial methylation and demethylation. Demethylation within pluripotency enhancers often occurs at ESC binding sites of pluripotency transcription factors...
May 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29656892/cancer-germline-antigen-expression-discriminates-clinical-outcome-to-ctla-4-blockade
#14
Sachet A Shukla, Pavan Bachireddy, Bastian Schilling, Christina Galonska, Qian Zhan, Clyde Bango, Rupert Langer, Patrick C Lee, Daniel Gusenleitner, Derin B Keskin, Mehrtash Babadi, Arman Mohammad, Andreas Gnirke, Kendell Clement, Zachary J Cartun, Eliezer M Van Allen, Diana Miao, Ying Huang, Alexandra Snyder, Taha Merghoub, Jedd D Wolchok, Levi A Garraway, Alexander Meissner, Jeffrey S Weber, Nir Hacohen, Donna Neuberg, Patrick R Potts, George F Murphy, Christine G Lian, Dirk Schadendorf, F Stephen Hodi, Catherine J Wu
CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has previously been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro...
April 19, 2018: Cell
https://www.readbyqxmd.com/read/29625070/a-clk3-hmga2-alternative-splicing-axis-impacts-human-hematopoietic-stem-cell-molecular-identity-throughout-development
#15
Marcella Cesana, Michael H Guo, Davide Cacchiarelli, Lara Wahlster, Jessica Barragan, Sergei Doulatov, Linda T Vo, Beatrice Salvatori, Cole Trapnell, Kendell Clement, Patrick Cahan, Kaloyan M Tsanov, Patricia M Sousa, Barbara Tazon-Vega, Adriano Bolondi, Federico M Giorgi, Andrea Califano, John L Rinn, Alexander Meissner, Joel N Hirschhorn, George Q Daley
While gene expression dynamics have been extensively cataloged during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators...
April 5, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29581568/author-correction-global-delay-in-nascent-strand-dna-methylation
#16
Jocelyn Charlton, Timothy L Downing, Zachary D Smith, Hongcang Gu, Kendell Clement, Ramona Pop, Veronika Akopian, Sven Klages, David P Santos, Alexander M Tsankov, Bernd Timmermann, Michael J Ziller, Evangelos Kiskinis, Andreas Gnirke, Alexander Meissner
Following online publication of this article, the Gene Expression Omnibus records corresponding to accession codes GSM2406773, MN-d6, and GSM2406772, MN-d14, listed in the data availability statement were deleted. The data are now available under accession codes GSM3039355, WGBS_hESC_WT_D6_R4 (MN day 6), and GSM3039351, WGBS_hESC_WT_D14_R4 (MN day 14), and the data availability statement has been updated with the new accession codes in the HTML and PDF versions of the article.
April 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29551301/dissecting-the-functional-consequences-of-de-novo-dna-methylation-dynamics-in-human-motor-neuron-differentiation-and-physiology
#17
Michael J Ziller, Juan A Ortega, Katharina A Quinlan, David P Santos, Hongcang Gu, Eric J Martin, Christina Galonska, Ramona Pop, Susanne Maidl, Alba Di Pardo, Mei Huang, Herbert Y Meltzer, Andreas Gnirke, C J Heckman, Alexander Meissner, Evangelos Kiskinis
The somatic DNA methylation (DNAme) landscape is established early in development but remains highly dynamic within focal regions that overlap with gene regulatory elements. The significance of these dynamic changes, particularly in the central nervous system, remains unresolved. Here, we utilize a powerful human embryonic stem cell differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNAme machinery. We quantitatively dissect the role of DNAme in directing somatic cell fate with high-resolution genome-wide bisulfite-, bulk-, and single-cell-RNA sequencing...
April 5, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29549299/using-unique-surface-patterns-of-injection-moulded-plastic-components-as-an-image-based-physical-unclonable-function-for-secure-component-identification
#18
Benedikt Wigger, Thomas Meissner, Alexander Förste, Volker Jetter, André Zimmermann
A Physical Unclonable Function uses random and inherent properties of a physical entity and can be used to uniquely identify components e.g., for anti-counterfeiting purposes. In this work we demonstrate that the surface patterns of injection moulded plastic components themselves are inherently unique and hence can be used as a PUF for reliable and secure identification. We further demonstrate that these unique surface patterns are easily accessible since they can be photographed with a simple camera set-up...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29531288/global-delay-in-nascent-strand-dna-methylation
#19
Jocelyn Charlton, Timothy L Downing, Zachary D Smith, Hongcang Gu, Kendell Clement, Ramona Pop, Veronika Akopian, Sven Klages, David P Santos, Alexander M Tsankov, Bernd Timmermann, Michael J Ziller, Evangelos Kiskinis, Andreas Gnirke, Alexander Meissner
Cytosine methylation is widespread among organisms and essential for mammalian development. In line with early postulations of an epigenetic role in gene regulation, symmetric CpG methylation can be mitotically propagated over many generations with extraordinarily high fidelity. Here, we combine BrdU labeling and immunoprecipitation with genome-wide bisulfite sequencing to explore the inheritance of cytosine methylation onto newly replicated DNA in human cells. Globally, we observe a pronounced lag between the copying of genetic and epigenetic information in embryonic stem cells that is reconsolidated within hours to accomplish faithful mitotic transmission...
April 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29435496/zika-virus-alters-dna-methylation-of-neural-genes-in-an-organoid-model-of-the-developing-human-brain
#20
Sylvie Janssens, Michael Schotsaert, Rahul Karnik, Vinod Balasubramaniam, Marion Dejosez, Alexander Meissner, Adolfo García-Sastre, Thomas P Zwaka
Zika virus (ZIKV) infection during early pregnancy can cause microcephaly and associated defects at birth, but whether it can induce neurologic sequelae that appear later in life remains unclear. Using a model of the developing brain based on embryonic stem cell-derived brain organoids, we studied the impact of ZIKV infection on the DNA methylation pattern across the entire genome in selected neural cell types. The virus unexpectedly alters the DNA methylome of neural progenitors, astrocytes, and differentiated neurons at genes that have been implicated in the pathogenesis of a number of brain disorders, most prominently mental retardation and schizophrenia...
January 2018: MSystems
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