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Marc Kirschner

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https://www.readbyqxmd.com/read/29595474/size-uniformity-of-animal-cells-is-actively-maintained-by-a-p38-mapk-dependent-regulation-of-g1-length
#1
Shixuan Liu, Miriam Bracha Ginzberg, Nish Patel, Marc Hild, Bosco Leung, Zhengda Li, Yen-Chi Chen, Nancy Chang, Yuan Wang, Ceryl Tan, Shulamit Diena, William Trimble, Larry Wasserman, Jeremy L Jenkins, Marc W Kirschner, Ran Kafri
Animal cells within a tissue typically display a striking regularity in their size. To date, the molecular mechanisms that control this uniformity are still unknown. We have previously shown that size uniformity in animal cells is promoted, in part, by size-dependent regulation of G1 length. To identify the molecular mechanisms underlying this process, we performed a large-scale small molecule screen and found that the p38 MAPK pathway is involved in coordinating cell size and cell cycle progression. Small cells display higher p38 activity and spend more time in G1 than larger cells...
March 29, 2018: ELife
https://www.readbyqxmd.com/read/29524024/assessing-abrasion-of-orthodontic-surface-sealants-using-a-modified-ophthalmic-optical-coherence-tomography-device
#2
Sinan Şen, Ralf Erber, Kevin Kunzmann, Stefanie Kirschner, Vanessa Weyer, Lothar Schilling, Marc A Brockmann, Stefan Rues, Gül Orhan, Christopher J Lux, Sebastian Zingler
OBJECTIVE: Optical coherence tomography (OCT) is a clinical standard in ophthalmology. Currently, its application in dentistry is gaining increasing interest. In this study, we tested the possibility to use a modified commercially available spectral domain OCT (SD-OCT) to assess the layer thickness of orthodontic surface sealants. MATERIALS AND METHODS: Reference samples of surface sealants for calibration and repeatability testing were measured using a micrometer screw...
March 9, 2018: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29489754/the-landscape-of-genomic-alterations-across-childhood-cancers
#3
Susanne N Gröbner, Barbara C Worst, Joachim Weischenfeldt, Ivo Buchhalter, Kortine Kleinheinz, Vasilisa A Rudneva, Pascal D Johann, Gnana Prakash Balasubramanian, Maia Segura-Wang, Sebastian Brabetz, Sebastian Bender, Barbara Hutter, Dominik Sturm, Elke Pfaff, Daniel Hübschmann, Gideon Zipprich, Michael Heinold, Jürgen Eils, Christian Lawerenz, Serap Erkek, Sander Lambo, Sebastian Waszak, Claudia Blattmann, Arndt Borkhardt, Michaela Kuhlen, Angelika Eggert, Simone Fulda, Manfred Gessler, Jenny Wegert, Roland Kappler, Daniel Baumhoer, Stefan Burdach, Renate Kirschner-Schwabe, Udo Kontny, Andreas E Kulozik, Dietmar Lohmann, Simone Hettmer, Cornelia Eckert, Stefan Bielack, Michaela Nathrath, Charlotte Niemeyer, Günther H Richter, Johannes Schulte, Reiner Siebert, Frank Westermann, Jan J Molenaar, Gilles Vassal, Hendrik Witt, Birgit Burkhardt, Christian P Kratz, Olaf Witt, Cornelis M van Tilburg, Christof M Kramm, Gudrun Fleischhack, Uta Dirksen, Stefan Rutkowski, Michael Frühwald, Katja von Hoff, Stephan Wolf, Thomas Klingebiel, Ewa Koscielniak, Pablo Landgraf, Jan Koster, Adam C Resnick, Jinghui Zhang, Yanling Liu, Xin Zhou, Angela J Waanders, Danny A Zwijnenburg, Pichai Raman, Benedikt Brors, Ursula D Weber, Paul A Northcott, Kristian W Pajtler, Marcel Kool, Rosario M Piro, Jan O Korbel, Matthias Schlesner, Roland Eils, David T W Jones, Peter Lichter, Lukas Chavez, Marc Zapatka, Stefan M Pfister
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers...
February 28, 2018: Nature
https://www.readbyqxmd.com/read/29347832/wire-placement-in-the-sustentaculum-tali-using-a-2d-projection-based-software-application-for-mobile-c-arms-cadaveric-study
#4
Benedict Swartman, Dirk Frere, Wei Wei, Marc Schnetzke, Stephan Grechenig, Amir Matityahu, Nils Beisemann, Holger Keil, Jochen Franke, Paul Alfred Grützner, Sven Yves Vetter
BACKGROUND: Indirect screw fixation of the sustentaculum tali in the lateral-medial direction can be challenging due to the complex calcaneal anatomy. A novel 2-dimensional (2D) projection-based software application detects Kirschner wires (K-wires) and visualizes their intended direction as a colored trajectory. The aim of this prospectively randomized cadaver study was to investigate whether the software would facilitate the indirect K-wire placement in the sustentaculum tali. METHODS: In 20 cadaver foot specimens, K-wires were placed indirectly in the sustentaculum tali by an experienced and an inexperienced surgeon, with and without using the application...
April 2018: Foot & Ankle International
https://www.readbyqxmd.com/read/29337984/anteroposterior-axis-patterning-by-early-canonical-wnt-signaling-during-hemichordate-development
#5
Sébastien Darras, Jens H Fritzenwanker, Kevin R Uhlinger, Ellyn Farrelly, Ariel M Pani, Imogen A Hurley, Rachael P Norris, Michelle Osovitz, Mark Terasaki, Mike Wu, Jochanan Aronowicz, Marc Kirschner, John C Gerhart, Christopher J Lowe
The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from vertebrate embryogenesis as well as planarian regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling endows cells with positional information along the A/P axis. Outside of these phyla, there is strong support for a conserved role of cWnt signaling in the repression of anterior fates, but little comparative support for a conserved role in promotion of posterior fates...
January 2018: PLoS Biology
https://www.readbyqxmd.com/read/29232698/low-energy-extracorporeal-shockwave-therapy-eswt-improves-metaphyseal-fracture-healing-in-an-osteoporotic-rat-model
#6
Gina A Mackert, Matthias Schulte, Christoph Hirche, Dimitra Kotsougiani, Julian Vogelpohl, Bernd Hoener, Teresa Fiebig, Stefanie Kirschner, Marc A Brockmann, Marcus Lehnhardt, Ulrich Kneser, Leila Harhaus
PURPOSE: As result of the current demographic changes, osteoporosis and osteoporotic fractures are becoming an increasing social and economic burden. In this experimental study, extracorporeal shock wave therapy (ESWT), was evaluated as a treatment option for the improvement of osteoporotic fracture healing. METHODS: A well-established fracture model in the metaphyseal tibia in the osteoporotic rat was used. 132 animals were divided into 11 groups, with 12 animals each, consisting of one sham-operated group and 10 ovariectomized (osteoporotic) groups, of which 9 received ESWT treatment...
2017: PloS One
https://www.readbyqxmd.com/read/29183978/proteomics-of-phosphorylation-and-protein-dynamics-during-fertilization-and-meiotic-exit-in-the-xenopus-egg
#7
Marc Presler, Elizabeth Van Itallie, Allon M Klein, Ryan Kunz, Margaret L Coughlin, Leonid Peshkin, Steven P Gygi, Martin Wühr, Marc W Kirschner
Fertilization releases the meiotic arrest and initiates the events that prepare the egg for the ensuing developmental program. Protein degradation and phosphorylation are known to regulate protein activity during this process. However, the full extent of protein loss and phosphoregulation is still unknown. We examined absolute protein and phosphosite dynamics of the fertilization response by mass spectrometry-based proteomics in electroactivated eggs. To do this, we developed an approach for calculating the stoichiometry of phosphosites from multiplexed proteomics that is compatible with dynamic, stable, and multisite phosphorylation...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28990928/mouse-embryonic-stem-cells-can-differentiate-via-multiple-paths-to-the-same-state
#8
James Alexander Briggs, Victor C Li, Seungkyu Lee, Clifford J Woolf, Allon Klein, Marc W Kirschner
In embryonic development, cells differentiate through stereotypical sequences of intermediate states to generate particular mature fates. By contrast, driving differentiation by ectopically expressing terminal transcription factors (direct programming) can generate similar fates by alternative routes. How differentiation in direct programming relates to embryonic differentiation is unclear. We applied single-cell RNA sequencing to compare two motor neuron differentiation protocols: a standard protocol approximating the embryonic lineage, and a direct programming method...
October 9, 2017: ELife
https://www.readbyqxmd.com/read/28885975/kinesin-superfamily-protein-kif26b-links-wnt5a-ror-signaling-to-the-control-of-cell-and-tissue-behaviors-in-vertebrates
#9
Michael W Susman, Edith P Karuna, Ryan C Kunz, Taranjit S Gujral, Andrea V Cantú, Shannon S Choi, Brigette Y Jong, Kyoko Okada, Michael K Scales, Jennie Hum, Linda S Hu, Marc W Kirschner, Ryuichi Nishinakamura, Soichiro Yamada, Diana J Laird, Li-En Jao, Steven P Gygi, Michael E Greenberg, Hsin-Yi Henry Ho
Wnt5a-Ror signaling constitutes a developmental pathway crucial for embryonic tissue morphogenesis, reproduction and adult tissue regeneration, yet the molecular mechanisms by which the Wnt5a-Ror pathway mediates these processes are largely unknown. Using a proteomic screen, we identify the kinesin superfamily protein Kif26b as a downstream target of the Wnt5a-Ror pathway. Wnt5a-Ror, through a process independent of the canonical Wnt/β-catenin-dependent pathway, regulates the cellular stability of Kif26b by inducing its degradation via the ubiquitin-proteasome system...
September 8, 2017: ELife
https://www.readbyqxmd.com/read/28723573/proteomic-and-metabolomic-characterization-of-a-mammalian-cellular-transition-from-quiescence-to-proliferation
#10
Ho-Joon Lee, Mark P Jedrychowski, Arunachalam Vinayagam, Ning Wu, Ng Shyh-Chang, Yanhui Hu, Chua Min-Wen, Jodene K Moore, John M Asara, Costas A Lyssiotis, Norbert Perrimon, Steven P Gygi, Lewis C Cantley, Marc W Kirschner
There exist similarities and differences in metabolism and physiology between normal proliferative cells and tumor cells. Once a cell enters the cell cycle, metabolic machinery is engaged to facilitate various processes. The kinetics and regulation of these metabolic changes have not been properly evaluated. To correlate the orchestration of these processes with the cell cycle, we analyzed the transition from quiescence to proliferation of a non-malignant murine pro-B lymphocyte cell line in response to IL-3...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28689658/conformational-landscape-of-the-p28-bound-human-proteasome-regulatory-particle
#11
Ying Lu, Jiayi Wu, Yuanchen Dong, Shuobing Chen, Shuangwu Sun, Yong-Bei Ma, Qi Ouyang, Daniel Finley, Marc W Kirschner, Youdong Mao
The proteasome holoenzyme is activated by its regulatory particle (RP) consisting of two subcomplexes, the lid and the base. A key event in base assembly is the formation of a heterohexameric ring of AAA-ATPases, which is guided by at least four RP assembly chaperones in mammals: PAAF1, p28/gankyrin, p27/PSMD9, and S5b. Using cryogenic electron microscopy, we analyzed the non-AAA structure of the p28-bound human RP at 4.5 Å resolution and determined seven distinct conformations of the Rpn1-p28-AAA subcomplex within the p28-bound RP at subnanometer resolutions...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28668406/vessel-shape-alterations-of-the-vertebrobasilar-arteries-in-mucopolysaccharidosis-type-iva-morquio-a-patients
#12
Yasemin Tanyildizi, Seyfullah Gökce, Federico Marini, Anna K Mayer, Stefanie Kirschner, Julia B Hennermann, Marc A Brockmann
PURPOSE: Main symptom of mucopolysaccharidosis type IVa (MPS IVa) is progressive systemic skeletal dysplasia. This is routinely monitored by cerebral and spinal MRI. The vascular system is generally not in the primary focus of interest. In our population of MPS IVa patients we observed vessel shape alterations of the vertebrobasilar arteries, which has not been described before. MATERIAL AND METHODS: MRI-datasets of 26 patients with MPS IVa acquired between 2008 and 2015 were eligible for retrospective analysis of the vertebrobasilar arteries...
August 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28644940/percutaneous-treatment-of-unstable-scaphoid-waist-fractures
#13
Andrew P Matson, Ryan M Garcia, Marc J Richard, Fraser J Leversedge, J Mack Aldridge, David S Ruch
BACKGROUND: Percutaneous techniques have been described for the treatment of nondisplaced scaphoid fractures, although less information has been reported about outcomes for unstable, displaced fractures. The aim of this study was to evaluate the union and complication rates following manual closed reduction and percutaneous screw placement for a consecutive series of unstable, displaced scaphoid fractures. METHODS: A total of 28 patients (average age, 27 years; 22 male/6 female) were treated for isolated unstable displaced scaphoid waist fractures...
July 2017: Hand: Official Journal of the American Association for Hand Surgery
https://www.readbyqxmd.com/read/28632594/outcome-of-early-and-late-diagnosed-essex-lopresti-injury
#14
Marc Schnetzke, Felix Porschke, Karin Hoppe, Stefan Studier-Fischer, Paul-Alfred Gruetzner, Thorsten Guehring
BACKGROUND: The aim of this study was to investigate the outcomes in a large series of Essex-Lopresti injuries (ELIs) and to compare patients with early and late diagnoses. METHODS: Thirty-one patients with an ELI (average age and standard deviation [SD], 46 ± 10 years) who were followed for a minimum of 2 years were included in the study. Patients were grouped according to whether the ELI had been diagnosed early (on the day of the injury) or late (>4 weeks after the radial head injury)...
June 21, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/28416665/hippo-pathway-mediates-resistance-to-cytotoxic-drugs
#15
Taranjit S Gujral, Marc W Kirschner
Chemotherapy is widely used for cancer treatment, but its effectiveness is limited by drug resistance. Here, we report a mechanism by which cell density activates the Hippo pathway, which in turn inactivates YAP, leading to changes in the regulation of genes that control the intracellular concentrations of gemcitabine and several other US Food and Drug Administration (FDA)-approved oncology drugs. Hippo inactivation sensitizes a diverse panel of cell lines and human tumors to gemcitabine in 3D spheroid, mouse xenografts, and patient-derived xenograft models...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28359158/relevant-insertion-site-anatomy-of-the-conventus-distal-radius-system
#16
Jacob Duncan, Marc Trzeciak
BACKGROUND: The Conventus Distal Radius System (DRS) is an intramedullary fixation scaffold inserted into the lateral aspect of the distal radius. The purpose of this study was to identify insertion site anatomy to illustrate risks associated with the minimally invasive nature of radial-sided implant application. METHODS: Ten cadavers were utilized. Using fluoroscopy, the 1.1-mm Kirschner wire and template was introduced per manufacturer's guidelines, access guide assembled, and dissection carried out to the superficial radial nerve (SRN) with preservation of the native location...
March 1, 2017: Hand: Official Journal of the American Association for Hand Surgery
https://www.readbyqxmd.com/read/28199398/a-segmentation-based-volumetric-approach-to-localize-and-quantify-cerebral-vasospasm-based-on-tomographic-imaging-data
#17
Axel Neulen, Tobias Pantel, Michael Kosterhon, Stefanie Kirschner, Marc A Brockmann, Sven R Kantelhardt, Alf Giese, Serge C Thal
INTRODUCTION: Quantification of cerebral vasospasm after subarachnoid hemorrhage (SAH) is crucial in animal studies as well as clinical routine. We have developed a method for computer-based volumetric assessment of intracranial blood vessels from cross-sectional imaging data. Here we demonstrate the quantification of vasospasm from micro computed tomography (micro-CT) data in a rodent SAH model and the transferability of the volumetric approach to clinical data. METHODS: We obtained rodent data by performing an ex vivo micro-CT of murine brains after sham surgery or SAH by endovascular filament perforation on day 3 post hemorrhage...
2017: PloS One
https://www.readbyqxmd.com/read/28174173/the-apc-c-e3-ligase-complex-activator-fzr1-restricts-braf-oncogenic-function
#18
Lixin Wan, Ming Chen, Juxiang Cao, Xiangpeng Dai, Qing Yin, Jinfang Zhang, Su-Jung Song, Ying Lu, Jing Liu, Hiroyuki Inuzuka, Jesse M Katon, Kelsey Berry, Jacqueline Fung, Christopher Ng, Pengda Liu, Min Sup Song, Lian Xue, Roderick T Bronson, Marc W Kirschner, Rutao Cui, Pier Paolo Pandolfi, Wenyi Wei
BRAF drives tumorigenesis by coordinating the activation of the RAS/RAF/MEK/ERK oncogenic signaling cascade. However, upstream pathways governing BRAF kinase activity and protein stability remain undefined. Here, we report that in primary cells with active APCFZR1 , APCFZR1 earmarks BRAF for ubiquitination-mediated proteolysis, whereas in cancer cells with APC-free FZR1, FZR1 suppresses BRAF through disrupting BRAF dimerization. Moreover, we identified FZR1 as a direct target of ERK and CYCLIN D1/CDK4 kinases...
April 2017: Cancer Discovery
https://www.readbyqxmd.com/read/27829015/imaging-of-orthotopic-glioblastoma-xenografts-in-mice-using-a-clinical-ct-scanner-comparison-with-micro-ct-and-histology
#19
COMPARATIVE STUDY
Stefanie Kirschner, Bettina Mürle, Manuela Felix, Anna Arns, Christoph Groden, Frederik Wenz, Andreas Hug, Gerhard Glatting, Martin Kramer, Frank A Giordano, Marc A Brockmann
PURPOSE: There is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated. MATERIALS AND METHODS: 2.5x106 U87MG cells were orthotopically implanted in NOD/SCID/ᵞc-/- mice (n = 9). Mice underwent contrast-enhanced (300 μl Iomeprol i...
2016: PloS One
https://www.readbyqxmd.com/read/27791164/structural-basis-for-dynamic-regulation-of-the-human-26s-proteasome
#20
Shuobing Chen, Jiayi Wu, Ying Lu, Yong-Bei Ma, Byung-Hoon Lee, Zhou Yu, Qi Ouyang, Daniel J Finley, Marc W Kirschner, Youdong Mao
The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitylated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. Using cryoelectron microscopy, we determined a near-atomic-resolution structure of the 2.5-MDa human proteasome in its ground state, as well as subnanometer-resolution structures of the holoenzyme in three alternative conformational states...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
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