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EMBO Reports

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https://www.readbyqxmd.com/read/28202491/organoid-technologies-meet-genome-engineering
#1
REVIEW
Jing Nie, Eri Hashino
Three-dimensional (3D) stem cell differentiation cultures recently emerged as a novel model system for investigating human embryonic development and disease progression in vitro, complementing existing animal and two-dimensional (2D) cell culture models. Organoids, the 3D self-organizing structures derived from pluripotent or somatic stem cells, can recapitulate many aspects of structural organization and functionality of their in vivo organ counterparts, thus holding great promise for biomedical research and translational applications...
February 15, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28193623/restricted-access-spatial-sequestration-of-damaged-proteins-during-stress-and-aging
#2
REVIEW
Sandra Malmgren Hill, Sarah Hanzén, Thomas Nyström
The accumulation of damaged and aggregated proteins is a hallmark of aging and increased proteotoxic stress. To limit the toxicity of damaged and aggregated proteins and to ensure that the damage is not inherited by succeeding cell generations, a system of spatial quality control operates to sequester damaged/aggregated proteins into inclusions at specific protective sites. Such spatial sequestration and asymmetric segregation of damaged proteins have emerged as key processes required for cellular rejuvenation...
February 13, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28193622/from-imitation-to-inspiration-biomimicry-experiences-a-revival-driven-by-a-more-systematic-approach-to-explore-nature-s-inventions-for-human-use
#3
https://www.readbyqxmd.com/read/28188145/structural-studies-of-rfc-c-tf18-reveal-a-novel-chromatin-recruitment-role-for-dcc1
#4
Benjamin O Wade, Hon Wing Liu, Catarina P Samora, Frank Uhlmann, Martin R Singleton
Replication factor C complexes load and unload processivity clamps from DNA and are involved in multiple DNA replication and repair pathways. The RFC(C)(tf18) variant complex is required for activation of the intra-S-phase checkpoint at stalled replication forks and aids the establishment of sister chromatid cohesion. Unlike other RFC complexes, RFC(C)(tf18) contains two non-Rfc subunits, Dcc1 and Ctf8. Here, we present the crystal structure of the Dcc1-Ctf8 heterodimer bound to the C-terminus of Ctf18. We find that the C-terminus of Dcc1 contains three-winged helix domains, which bind to both ssDNA and dsDNA We further show that these domains are required for full recruitment of the complex to chromatin, and correct activation of the replication checkpoint...
February 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28183853/mark4-inhibits-hippo-signaling-to-promote-proliferation-and-migration-of-breast-cancer-cells
#5
Emad Heidary Arash, Ahmed Shiban, Siyuan Song, Liliana Attisano
The Hippo pathway is a critical regulator of tissue size, and aberrations in pathway regulation lead to cancer. MST1/2 and LATS1/2 kinases comprise the core of the pathway that, in association with adaptor proteins SAV and MOB, functions in a sequential manner to phosphorylate and inhibit the transcription factors YAP and TAZ. Here we identify mammalian MARK family members as activators of YAP/TAZ. We show that depletion of MARK4 in MDA-MB-231 breast cancer cells results in the loss of nuclear YAP/TAZ and decreases the expression of YAP/TAZ targets...
February 9, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28179364/trump-s-travel-travesty
#6
EDITORIAL
Holger Breithaupt, Bernd Pulverer
No abstract text is available yet for this article.
February 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28174209/oncoprotein-cip2a-is-stabilized-via-interaction-with-tumor-suppressor-pp2a-b56
#7
Jiao Wang, Juha Okkeri, Karolina Pavic, Zhizhi Wang, Otto Kauko, Tuuli Halonen, Grzegorz Sarek, Päivi M Ojala, Zihe Rao, Wenqing Xu, Jukka Westermarck
Protein phosphatase 2A (PP2A) is a critical human tumor suppressor. Cancerous inhibitor of PP2A (CIP2A) supports the activity of several critical cancer drivers (Akt, MYC, E2F1) and promotes malignancy in most cancer types via PP2A inhibition. However, the 3D structure of CIP2A has not been solved, and it remains enigmatic how it interacts with PP2A. Here, we show by yeast two-hybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an N-terminal CIP2A fragment (amino acids 1-560) at 3...
February 7, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28174208/l-opa1-regulates-mitoflash-biogenesis-independently-from-membrane-fusion
#8
Manon Rosselin, Jaime Santo-Domingo, Flavien Bermont, Marta Giacomello, Nicolas Demaurex
Mitochondrial flashes mediated by optic atrophy 1 (OPA1) fusion protein are bioenergetic responses to stochastic drops in mitochondrial membrane potential (Δψm) whose origin is unclear. Using structurally distinct genetically encoded pH-sensitive probes, we confirm that flashes are matrix alkalinization transients, thereby establishing the pH nature of these events, which we renamed "mitopHlashes". Probes located in cristae or intermembrane space as verified by electron microscopy do not report pH changes during Δψm drops or respiratory chain inhibition...
February 7, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28167676/doping-and-drug-testing-anti-doping-work-must-be-transparent-and-adhere-to-good-scientific-practices-to-ensure-public-trust
#9
Erik Boye, Tore Skotland, Bjarne Østerud, Jon Nissen-Meyer
No abstract text is available yet for this article.
February 6, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28143880/a-pension-fund-for-european-scientists
#10
Vic Norris
No abstract text is available yet for this article.
January 31, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28126726/feel-the-beat-music-exploits-our-brain-s-ability-to-predict-and-the-dopamine-reward-system-to-instill-pleasure
#11
Katrin Weigmann
No abstract text is available yet for this article.
January 26, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28104734/mitochondrial-e3-ligase-march5-regulates-fundc1-to-fine-tune-hypoxic-mitophagy
#12
Ziheng Chen, Lei Liu, Qi Cheng, Yanjun Li, Hao Wu, Weilin Zhang, Yueying Wang, Sheikh Arslan Sehgal, Sami Siraj, Xiaohui Wang, Jun Wang, Yushan Zhu, Quan Chen
Mitophagy is an essential process for mitochondrial quality control and turnover. It is activated by two distinct pathways, one dependent on ubiquitin and the other dependent on receptors including FUNDC1. It is not clear whether these pathways coordinate to mediate mitophagy in response to stresses, or how mitophagy receptors sense stress signals to activate mitophagy. We find that the mitochondrial E3 ligase MARCH5, but not Parkin, plays a role in regulating hypoxia-induced mitophagy by ubiquitylating and degrading FUNDC1...
January 19, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28082314/a-cmc1-knockout-reveals-translation-independent-control-of-human-mitochondrial-complex-iv-biogenesis
#13
Myriam Bourens, Antoni Barrientos
Defects in mitochondrial respiratory chain complex IV (CIV) frequently cause encephalocardiomyopathies. Human CIV assembly involves 14 subunits of dual genetic origin and multiple nucleus-encoded ancillary factors. Biogenesis of the mitochondrion-encoded copper/heme-containing COX1 subunit initiates the CIV assembly process. Here, we show that the intermembrane space twin CX9C protein CMC1 forms an early CIV assembly intermediate with COX1 and two assembly factors, the cardiomyopathy proteins COA3 and COX14...
January 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28082312/a-single-miu-motif-of-mindy-1-recognizes-k48-linked-polyubiquitin-chains
#14
Yosua Adi Kristariyanto, Syed Arif Abdul Rehman, Simone Weidlich, Axel Knebel, Yogesh Kulathu
The eight different types of ubiquitin (Ub) chains that can be formed play important roles in diverse cellular processes. Linkage-selective recognition of Ub chains by Ub-binding domain (UBD)-containing proteins is central to coupling different Ub signals to specific cellular responses. The motif interacting with ubiquitin (MIU) is a small UBD that has been characterized for its binding to monoUb. The recently discovered deubiquitinase MINDY-1/FAM63A contains a tandem MIU repeat (tMIU) that is highly selective at binding to K48-linked polyUb...
January 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28077461/human-rif1-and-protein-phosphatase-1-stimulate-dna-replication-origin-licensing-but-suppress-origin-activation
#15
Shin-Ichiro Hiraga, Tony Ly, Javier Garzón, Zuzana Hořejší, Yoshi-Nobu Ohkubo, Akinori Endo, Chikashi Obuse, Simon J Boulton, Angus I Lamond, Anne D Donaldson
The human RIF1 protein controls DNA replication, but the molecular mechanism is largely unknown. Here, we demonstrate that human RIF1 negatively regulates DNA replication by forming a complex with protein phosphatase 1 (PP1) that limits phosphorylation-mediated activation of the MCM replicative helicase. We identify specific residues on four MCM helicase subunits that show hyperphosphorylation upon RIF1 depletion, with the regulatory N-terminal domain of MCM4 being particularly strongly affected. In addition to this role in limiting origin activation, we discover an unexpected new role for human RIF1-PP1 in mediating efficient origin licensing...
January 11, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28069610/an-incoherent-feed-forward-loop-mediates-robustness-and-tunability-in-a-plant-immune-network
#16
Akira Mine, Tatsuya Nobori, Maria C Salazar-Rondon, Thomas M Winkelmüller, Shajahan Anver, Dieter Becker, Kenichi Tsuda
Immune signaling networks must be tunable to alleviate fitness costs associated with immunity and, at the same time, robust against pathogen interferences. How these properties mechanistically emerge in plant immune signaling networks is poorly understood. Here, we discovered a molecular mechanism by which the model plant species Arabidopsis thaliana achieves robust and tunable immunity triggered by the microbe-associated molecular pattern, flg22. Salicylic acid (SA) is a major plant immune signal molecule...
January 9, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28119373/of-mice-and-crispr-the-post-crispr-future-of-the-mouse-as-a-model-system-for-the-human-condition
#17
Edison T Liu, Ewelina Bolcun-Filas, David S Grass, Cathleen Lutz, Steve Murray, Lenny Shultz, Nadia Rosenthal
No abstract text is available yet for this article.
February 2017: EMBO Reports
https://www.readbyqxmd.com/read/28115393/more-science-in-urban-development-scientific-evidence-is-crucial-for-managing-health-and-infrastructures-of-megacities
#18
Philip Hunter
No abstract text is available yet for this article.
February 2017: EMBO Reports
https://www.readbyqxmd.com/read/28082313/regulating-phage-therapy-the-biological-master-file-concept-could-help-to-overcome-regulatory-challenge-of-personalized-medicines
#19
Alan Fauconnier
No abstract text is available yet for this article.
February 2017: EMBO Reports
https://www.readbyqxmd.com/read/28082311/science-modernity-and-the-muslim-world-to-improve-scientific-research-in-muslim-countries-requires-profound-social-and-economic-liberalization-of-their-societies
#20
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