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Alexander Meissner

Kunihiko Hinohara, Hua-Jun Wu, Sébastien Vigneau, Thomas O McDonald, Kyomi J Igarashi, Kimiyo N Yamamoto, Thomas Madsen, Anne Fassl, Shawn B Egri, Malvina Papanastasiou, Lina Ding, Guillermo Peluffo, Ofir Cohen, Stephen C Kales, Madhu Lal-Nag, Ganesha Rai, David J Maloney, Ajit Jadhav, Anton Simeonov, Nikhil Wagle, Myles Brown, Alexander Meissner, Piotr Sicinski, Jacob D Jaffe, Rinath Jeselsohn, Alexander A Gimelbrant, Franziska Michor, Kornelia Polyak
No abstract text is available yet for this article.
February 11, 2019: Cancer Cell
Claire Meissner-Bernard, Yulia Dembitskaya, Laurent Venance, Alexander Fleischmann
Odor memories are exceptionally robust and essential for animal survival. The olfactory (piriform) cortex has long been hypothesized to encode odor memories, yet the cellular substrates for olfactory learning and memory remain unknown. Here, using intersectional, cFos-based genetic manipulations ("Fos tagging"), we show that olfactory fear conditioning activates sparse and distributed ensembles of neurons in the mouse piriform cortex. We demonstrate that chemogenetic silencing of these Fos-tagged piriform ensembles selectively interferes with odor fear memory retrieval but does not compromise basic odor detection and discrimination...
December 24, 2018: Current Biology: CB
Hans-Ulrich Klein, Cristin McCabe, Elizabeta Gjoneska, Sarah E Sullivan, Belinda J Kaskow, Anna Tang, Robert V Smith, Jishu Xu, Andreas R Pfenning, Bradley E Bernstein, Alexander Meissner, Julie A Schneider, Sara Mostafavi, Li-Huei Tsai, Tracy L Young-Pearse, David A Bennett, Philip L De Jager
Accumulation of tau and amyloid-β are two pathologic hallmarks of Alzheimer's disease. We conducted an epigenome-wide association study using the histone 3 lysine 9 acetylation (H3K9ac) mark in 669 aged human prefrontal cortices; in contrast with amyloid-β, tau protein burden had a broad effect on the epigenome, affecting 5,990 of 26,384 H3K9ac domains. Tau-related alterations aggregated in large genomic segments reflecting spatial chromatin organization, and the magnitude of these effects correlated with the segment's nuclear lamina association...
January 2019: Nature Neuroscience
Kunihiko Hinohara, Hua-Jun Wu, Sébastien Vigneau, Thomas O McDonald, Kyomi J Igarashi, Kimiyo N Yamamoto, Thomas Madsen, Anne Fassl, Shawn B Egri, Malvina Papanastasiou, Lina Ding, Guillermo Peluffo, Ofir Cohen, Stephen C Kales, Madhu Lal-Nag, Ganesha Rai, David J Maloney, Ajit Jadhav, Anton Simeonov, Nikhil Wagle, Myles Brown, Alexander Meissner, Piotr Sicinski, Jacob D Jaffe, Rinath Jeselsohn, Alexander A Gimelbrant, Franziska Michor, Kornelia Polyak
Members of the KDM5 histone H3 lysine 4 demethylase family are associated with therapeutic resistance, including endocrine resistance in breast cancer, but the underlying mechanism is poorly defined. Here we show that genetic deletion of KDM5A/B or inhibition of KDM5 activity increases sensitivity to anti-estrogens by modulating estrogen receptor (ER) signaling and by decreasing cellular transcriptomic heterogeneity. Higher KDM5B expression levels are associated with higher transcriptomic heterogeneity and poor prognosis in ER+ breast tumors...
November 14, 2018: Cancer Cell
Yingying Zhang, Jocelyn Charlton, Rahul Karnik, Isabel Beerman, Zachary D Smith, Hongcang Gu, Patrick Boyle, Xiaoli Mi, Kendell Clement, Ramona Pop, Andreas Gnirke, Derrick J Rossi, Alexander Meissner
DNA methylation plays an essential role in mammalian genomes and expression of the responsible enzymes is tightly controlled. Deregulation of the de novo DNA methyltransferase DNMT3B is frequently observed across cancer types, yet little is known about its ectopic genomic targets. Here, we used an inducible transgenic mouse model to delineate rules for abnormal DNMT3B targeting, as well as the constraints of its activity across different cell types. Our results explain the preferential susceptibility of certain CpG islands to aberrant methylation and point to transcriptional state and the associated chromatin landscape as the strongest predictors...
November 23, 2018: ELife
Emily Bernstein, Alexander Meissner, Miguel Ramalho-Santos
No abstract text is available yet for this article.
November 2018: Nature
Justin K Ichida, Kim A Staats, Brandi N Davis-Dusenbery, Kendell Clement, Kate E Galloway, Kimberly N Babos, Yingxiao Shi, Esther Y Son, Evangelos Kiskinis, Nicholas Atwater, Hongcang Gu, Andreas Gnirke, Alexander Meissner, Kevin Eggan
Advances in stem cell science allow the production of different cell types in vitro either through the recapitulation of developmental processes, often termed "directed differentiation," or the forced expression of lineage-specific transcription factors. Although cells produced by both approaches are increasingly used in translational applications, their quantitative similarity to their primary counterparts remains largely unresolved. To investigate the similarity between in vitro -derived and primary cell types, we harvested and purified mouse spinal motor neurons and compared them to motor neurons produced by transcription factor-mediated lineage conversion of fibroblasts or directed differentiation of pluripotent stem cells...
October 18, 2018: Development
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
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
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
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
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...
November 2018: International Journal of Nursing Studies
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
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
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
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
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...
November 2018: Pain Practice: the Official Journal of World Institute of Pain
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
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) promoter methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH mutation status, MGMT promoter methylation, and differentiation of low-grade versus high-grade glioma (LGG vs HGG) in newly diagnosed patients employing relaxation-compensated multipool chemical exchange saturation transfer (CEST) MRI at 7...
November 12, 2018: Neuro-oncology
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
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