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https://www.readbyqxmd.com/read/30237157/mutant-mrps5-affects-mitoribosomal-accuracy-and-confers-stress-related-behavioral-alterations
#1
Rashid Akbergenov, Stefan Duscha, Ann-Kristina Fritz, Reda Juskeviciene, Naoki Oishi, Karen Schmitt, Dimitri Shcherbakov, Youjin Teo, Heithem Boukari, Pietro Freihofer, Patricia Isnard-Petit, Björn Oettinghaus, Stephan Frank, Kader Thiam, Hubert Rehrauer, Eric Westhof, Jochen Schacht, Anne Eckert, David Wolfer, Erik C Böttger
The 1555 A to G substitution in mitochondrial 12S A-site rRNA is associated with maternally transmitted deafness of variable penetrance in the absence of otherwise overt disease. Here, we recapitulate the suggested A1555G-mediated pathomechanism in an experimental model of mitoribosomal mistranslation by directed mutagenesis of mitoribosomal protein MRPS5. We first establish that the ratio of cysteine/methionine incorporation and read-through of mtDNA-encoded MT-CO1 protein constitute reliable measures of mitoribosomal misreading...
September 20, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30237156/human-dignity-and-gene-editing-using-human-dignity-as-an-argument-against-modifying-the-human-genome-and-germline-is-a-logical-fallacy
#2
Iñigo de Miguel Beriain
No abstract text is available yet for this article.
September 20, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30232163/protein-palmitoylation-and-cancer
#3
REVIEW
Pin-Joe Ko, Scott J Dixon
Protein S-palmitoylation is a reversible post-translational modification that alters the localization, stability, and function of hundreds of proteins in the cell. S-palmitoylation is essential for the function of both oncogenes (e.g., NRAS and EGFR) and tumor suppressors (e.g., SCRIB, melanocortin 1 receptor). In mammalian cells, the thioesterification of palmitate to internal cysteine residues is catalyzed by 23 Asp-His-His-Cys (DHHC)-family palmitoyl S-acyltransferases while the removal of palmitate is catalyzed by serine hydrolases, including acyl-protein thioesterases (APTs)...
September 19, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30224412/netrin-1-dcc-mediated-plc%C3%AE-1-activation-is-required-for-axon-guidance-and-brain-structure-development
#4
Du-Seock Kang, Yong Ryoul Yang, Cheol Lee, BumWoo Park, Kwang Il Park, Jeong Kon Seo, Young Kyo Seo, HyungJoon Cho, Cocco Lucio, Pann-Ghill Suh
Coordinated expression of guidance molecules and their signal transduction are critical for correct brain wiring. Previous studies have shown that phospholipase C gamma1 (PLCγ1), a signal transducer of receptor tyrosine kinases, plays a specific role in the regulation of neuronal cell morphology and motility in vitro However, several questions remain regarding the extracellular stimulus that triggers PLCγ1 signaling and the exact role PLCγ1 plays in nervous system development. Here, we demonstrate that PLCγ1 mediates axonal guidance through a netrin-1/deleted in colorectal cancer (DCC) complex...
September 17, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30224411/the-dual-role-of-the-centrosome-in-organizing-the-microtubule-network-in-interphase
#5
Maria P Gavilan, Pablo Gandolfo, Fernando R Balestra, Francisco Arias, Michel Bornens, Rosa M Rios
Here, we address the regulation of microtubule nucleation during interphase by genetically ablating one, or two, of three major mammalian γ-TuRC-binding factors namely pericentrin, CDK5Rap2, and AKAP450. Unexpectedly, we find that while all of them participate in microtubule nucleation at the Golgi apparatus, they only modestly contribute at the centrosome where CEP192 has a more predominant function. We also show that inhibiting microtubule nucleation at the Golgi does not affect centrosomal activity, whereas manipulating the number of centrosomes with centrinone modifies microtubule nucleation activity of the Golgi apparatus...
September 17, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30224410/translation-acrobatics-how-cancer-cells-exploit-alternate-modes-of-translational-initiation
#6
REVIEW
Ashwin Sriram, Jonathan Bohlen, Aurelio A Teleman
Recent work has brought to light many different mechanisms of translation initiation that function in cells in parallel to canonical cap-dependent initiation. This has important implications for cancer. Canonical cap-dependent translation initiation is inhibited by many stresses such as hypoxia, nutrient limitation, proteotoxic stress, or genotoxic stress. Since cancer cells are often exposed to these stresses, they rely on alternate modes of translation initiation for protein synthesis and cell growth. Cancer mutations are now being identified in components of the translation machinery and in cis -regulatory elements of mRNAs, which both control translation of cancer-relevant genes...
September 17, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30224409/new-therapies-to-relieve-pain-the-search-for-more-efficient-and-safer-alternatives-to-opioid-pain-killers
#7
Philip Hunter
No abstract text is available yet for this article.
September 17, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30213795/sirt2-mediated-inactivation-of-p73-is-required-for-glioblastoma-tumorigenicity
#8
Kosuke Funato, Tomoatsu Hayashi, Kanae Echizen, Lumi Negishi, Naomi Shimizu, Ryo Koyama-Nasu, Yukiko Nasu-Nishimura, Yasuyuki Morishita, Viviane Tabar, Tomoki Todo, Yasushi Ino, Akitake Mukasa, Nobuhito Saito, Tetsu Akiyama
Glioblastoma is one of the most aggressive forms of cancers and has a poor prognosis. Genomewide analyses have revealed that a set of core signaling pathways, the p53, RB, and RTK pathways, are commonly deregulated in glioblastomas. However, the molecular mechanisms underlying the tumorigenicity of glioblastoma are not fully understood. Here, we show that the lysine deacetylase SIRT2 is required for the proliferation and tumorigenicity of glioblastoma cells, including glioblastoma stem cells. Furthermore, we demonstrate that SIRT2 regulates p73 transcriptional activity by deacetylation of its C-terminal lysine residues...
September 13, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30206190/single-cell-transcriptomics-reveals-distinct-inflammation-induced-microglia-signatures
#9
Carole Sousa, Anna Golebiewska, Suresh K Poovathingal, Tony Kaoma, Yolanda Pires-Afonso, Silvia Martina, Djalil Coowar, Francisco Azuaje, Alexander Skupin, Rudi Balling, Knut Biber, Simone P Niclou, Alessandro Michelucci
Microglia are specialized parenchymal-resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglial responses are thought to worsen CNS diseases; nevertheless, their impact during neuroinflammatory processes remains largely obscure. Here, using a combination of single-cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)-injected mice. By excluding the contribution of other immune CNS-resident and peripheral cells, we show that microglia isolated from LPS-injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes...
September 11, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30206189/usp7-and-usp47-deubiquitinases-regulate-nlrp3-inflammasome-activation
#10
Pablo Palazón-Riquelme, Jonathan D Worboys, Jack Green, Ana Valera, Fatima Martín-Sánchez, Carolina Pellegrini, David Brough, Gloria López-Castejón
The assembly and activation of the inflammasomes are tightly regulated by post-translational modifications, including ubiquitin. Deubiquitinases (DUBs) counteract the addition of ubiquitin and are essential regulators of immune signalling pathways, including those acting on the inflammasome. How DUBs control the assembly and activation of inflammasomes is unclear. Here, we show that the DUBs USP7 and USP47 regulate inflammasome activation in macrophages. Chemical inhibition of USP7 and USP47 blocks inflammasome formation, independently of transcription, by preventing ASC oligomerisation and speck formation...
September 11, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30206188/opposing-kinesin-complexes-queue-at-plus-tips-to-ensure-microtubule-catastrophe-at-cell-ends
#11
John C Meadows, Liam J Messin, Anton Kamnev, Theresa C Lancaster, Mohan K Balasubramanian, Robert A Cross, Jonathan Ba Millar
In fission yeast, the lengths of interphase microtubule (iMT) arrays are adapted to cell length to maintain cell polarity and to help centre the nucleus and cell division ring. Here, we show that length regulation of iMTs is dictated by spatially regulated competition between MT-stabilising Tea2/Tip1/Mal3 (Kinesin-7) and MT-destabilising Klp5/Klp6/Mcp1 (Kinesin-8) complexes at iMT plus ends. During MT growth, the Tea2/Tip1/Mal3 complex remains bound to the plus ends of iMT bundles, thereby restricting access to the plus ends by Klp5/Klp6/Mcp1, which accumulate behind it...
September 11, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30201800/vesicle-sub-pool-organization-at-inner-hair-cell-ribbon-synapses
#12
Rituparna Chakrabarti, Susann Michanski, Carolin Wichmann
The afferent inner hair cell synapse harbors the synaptic ribbon, which ensures a constant vesicle supply. Synaptic vesicles (SVs) are arranged in morphologically discernable pools, linked via filaments to the ribbon or the presynaptic membrane. We propose that filaments play a major role in SV resupply and exocytosis at the ribbon. Using advanced electron microscopy, we demonstrate that SVs are organized in sub-pools defined by the filament number per vesicle and its connections. Upon stimulation, SVs increasingly linked to other vesicles and to the ribbon, whereas single-tethered SVs dominated at the membrane...
September 10, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30201799/acetylation-of-sumo2-at-lysine-11-favors-the-formation-of-non-canonical-sumo-chains
#13
Anne Gärtner, Kristina Wagner, Soraya Hölper, Kathrin Kunz, Manuel S Rodriguez, Stefan Müller
Post-translational modifications by ubiquitin-related SUMO modifiers regulate cellular signaling networks and protein homeostasis. While SUMO1 is mainly conjugated to proteins as a monomer, SUMO2/3 can form polymeric chains. Poly-SUMOylation is best understood in the SUMO-targeted ubiquitin ligase (StUbL) pathway, where chains prime proteins for subsequent ubiquitylation by StUbLs. SUMO chains typically form in response to genotoxic or proteotoxic stress and are preferentially linked via lysine 11 of SUMO2/3...
September 10, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30185424/proportionate-and-scientifically-sound-risk-assessment-of-gene-edited-plants
#14
Josep M Casacuberta, Pere Puigdomènech
No abstract text is available yet for this article.
September 5, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30177555/is-it-time-to-put-a-humidifier-in-the-dry-domain-of-writing-scientific-papers-given-the-inaccessibility-of-many-research-papers-young-scientists-should-receive-more-formal-training-to-write-clear-understandable-and-even-enjoyable-papers
#15
https://www.readbyqxmd.com/read/30177554/macroh2a-histone-variants-limit-chromatin-plasticity-through-two-distinct-mechanisms
#16
Marek Kozlowski, David Corujo, Michael Hothorn, Iva Guberovic, Imke K Mandemaker, Charlotte Blessing, Judith Sporn, Arturo Gutierrez-Triana, Rebecca Smith, Thomas Portmann, Mathias Treier, Klaus Scheffzek, Sebastien Huet, Gyula Timinszky, Marcus Buschbeck, Andreas G Ladurner
MacroH2A histone variants suppress tumor progression and act as epigenetic barriers to induced pluripotency. How they impart their influence on chromatin plasticity is not well understood. Here, we analyze how the different domains of macroH2A proteins contribute to chromatin structure and dynamics. By solving the crystal structure of the macrodomain of human macroH2A2 at 1.7 Å, we find that its putative binding pocket exhibits marked structural differences compared with the macroH2A1.1 isoform, rendering macroH2A2 unable to bind ADP-ribose...
September 3, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30177553/ttyh1-regulates-embryonic-neural-stem-cell-properties-by-enhancing-the-notch-signaling-pathway
#17
Juwan Kim, Dasol Han, Sung-Hyun Byun, Mookwang Kwon, Jae Youl Cho, Samuel J Pleasure, Keejung Yoon
Despite growing evidence linking Drosophila melanogaster tweety-homologue 1 (Ttyh1) to normal mammalian brain development and cell proliferation, its exact role has not yet been determined. Here, we show that Ttyh1 is required for the maintenance of neural stem cell (NSC) properties as assessed by neurosphere formation and in vivo analyses of cell localization after in utero electroporation. We find that enhanced Ttyh1-dependent stemness of NSCs is caused by enhanced γ-secretase activity resulting in increased levels of Notch intracellular domain (NICD) production and activation of Notch targets...
September 3, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30166337/kit-ligand-has-a-critical-role-in-mouse-yolk-sac-and-aorta-gonad-mesonephros-hematopoiesis
#18
Emanuele Azzoni, Vincent Frontera, Kathleen E McGrath, Joe Harman, Joana Carrelha, Claus Nerlov, James Palis, Sten Eirik W Jacobsen, Marella Ftr de Bruijn
Few studies report on the in vivo requirement for hematopoietic niche factors in the mammalian embryo. Here, we comprehensively analyze the requirement for Kit ligand (Kitl) in the yolk sac and aorta-gonad-mesonephros (AGM) niche. In-depth analysis of loss-of-function and transgenic reporter mouse models show that Kitl-deficient embryos harbor decreased numbers of yolk sac erythro-myeloid progenitor (EMP) cells, resulting from a proliferation defect following their initial emergence. This EMP defect causes a dramatic decrease in fetal liver erythroid cells prior to the onset of hematopoietic stem cell (HSC)-derived erythropoiesis, and a reduction in tissue-resident macrophages...
August 30, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30166336/sequentially-acting-sox-proteins-orchestrate-astrocyte-and-oligodendrocyte-specific-gene-expression
#19
Susanne Klum, Cécile Zaouter, Zhanna Alekseenko, Åsa K Björklund, Daniel W Hagey, Johan Ericson, Jonas Muhr, Maria Bergsland
SOX transcription factors have important roles during astrocyte and oligodendrocyte development, but how glial genes are specified and activated in a sub-lineage-specific fashion remains unknown. Here, we define glial-specific gene expression in the developing spinal cord using single-cell RNA-sequencing. Moreover, by ChIP-seq analyses we show that these glial gene sets are extensively preselected already in multipotent neural precursor cells through prebinding by SOX3. In the subsequent lineage-restricted glial precursor cells, astrocyte genes become additionally targeted by SOX9 at DNA regions strongly enriched for Nfi binding motifs...
August 30, 2018: EMBO Reports
https://www.readbyqxmd.com/read/30158143/scientific-honesty-and-publicly-shared-lab-notebooks-sharing-lab-notebooks-along-with-publication-would-increase-transparency-and-help-to-improve-honesty-when-reporting-results
#20
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