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Nature Communications

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https://www.readbyqxmd.com/read/28232751/clk-dependent-exon-recognition-and-conjoined-gene-formation-revealed-with-a-novel-small-molecule-inhibitor
#1
Tyler Funnell, Shinya Tasaki, Arusha Oloumi, Shinsuke Araki, Esther Kong, Damian Yap, Yusuke Nakayama, Christopher S Hughes, S-W Grace Cheng, Hirokazu Tozaki, Misa Iwatani, Satoshi Sasaki, Tomohiro Ohashi, Tohru Miyazaki, Nao Morishita, Daisuke Morishita, Mari Ogasawara-Shimizu, Momoko Ohori, Shoichi Nakao, Masatoshi Karashima, Masaya Sano, Aiko Murai, Toshiyuki Nomura, Noriko Uchiyama, Tomohiro Kawamoto, Ryujiro Hara, Osamu Nakanishi, Karey Shumansky, Jamie Rosner, Adrian Wan, Steven McKinney, Gregg B Morin, Atsushi Nakanishi, Sohrab Shah, Hiroyoshi Toyoshiba, Samuel Aparicio
CDC-like kinase phosphorylation of serine/arginine-rich proteins is central to RNA splicing reactions. Yet, the genomic network of CDC-like kinase-dependent RNA processing events remains poorly defined. Here, we explore the connectivity of genomic CDC-like kinase splicing functions by applying graduated, short-exposure, pharmacological CDC-like kinase inhibition using a novel small molecule (T3) with very high potency, selectivity, and cell-based stability. Using RNA-Seq, we define CDC-like kinase-responsive alternative splicing events, the large majority of which monotonically increase or decrease with increasing CDC-like kinase inhibition...
December 2017: Nature Communications
https://www.readbyqxmd.com/read/28232750/molecular-dynamics-simulations-reveal-ligand-controlled-positioning-of-a-peripheral-protein-complex-in-membranes
#2
Steven M Ryckbosch, Paul A Wender, Vijay S Pande
Bryostatin is in clinical trials for Alzheimer's disease, cancer, and HIV/AIDS eradication. It binds to protein kinase C competitively with diacylglycerol, the endogenous protein kinase C regulator, and plant-derived phorbol esters, but each ligand induces different activities. Determination of the structural origin for these differing activities by X-ray analysis has not succeeded due to difficulties in co-crystallizing protein kinase C with relevant ligands. More importantly, static, crystal-lattice bound complexes do not address the influence of the membrane on the structure and dynamics of membrane-associated proteins...
December 2017: Nature Communications
https://www.readbyqxmd.com/read/28232749/genomic-rna-folding-mediates-assembly-of-human-parechovirus
#3
Shabih Shakeel, Eric C Dykeman, Simon J White, Ari Ora, Joseph J B Cockburn, Sarah J Butcher, Peter G Stockley, Reidun Twarock
Assembly of the major viral pathogens of the Picornaviridae family is poorly understood. Human parechovirus 1 is an example of such viruses that contains 60 short regions of ordered RNA density making identical contacts with the protein shell. We show here via a combination of RNA-based systematic evolution of ligands by exponential enrichment, bioinformatics analysis and reverse genetics that these RNA segments are bound to the coat proteins in a sequence-specific manner. Disruption of either the RNA coat protein recognition motif or its contact amino acid residues is deleterious for viral assembly...
December 2017: Nature Communications
https://www.readbyqxmd.com/read/28232748/ultrafast-radiative-heat-transfer
#4
Renwen Yu, Alejandro Manjavacas, F Javier García de Abajo
Light absorption in conducting materials produces heating of their conduction electrons, followed by relaxation into phonons within picoseconds, and subsequent diffusion into the surrounding media over longer timescales. This conventional picture of optical heating is supplemented by radiative cooling, which typically takes place at an even lower pace, only becoming relevant for structures held in vacuum or under extreme thermal isolation. Here, we reveal an ultrafast radiative cooling regime between neighboring plasmon-supporting graphene nanostructures in which noncontact heat transfer becomes a dominant channel...
December 2017: Nature Communications
https://www.readbyqxmd.com/read/28232747/in-situ-click-chemistry-generation-of-cyclooxygenase-2-inhibitors
#5
Atul Bhardwaj, Jatinder Kaur, Melinda Wuest, Frank Wuest
Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors...
December 2017: Nature Communications
https://www.readbyqxmd.com/read/28232746/repeated-evolution-of-soldier-sub-castes-suggests-parasitism-drives-social-complexity-in-stingless-bees
#6
Christoph Grüter, Francisca H I D Segers, Cristiano Menezes, Ayrton Vollet-Neto, Tiago Falcón, Lucas von Zuben, Márcia M G Bitondi, Fabio S Nascimento, Eduardo A B Almeida
The differentiation of workers into morphological castes represents an important evolutionary innovation that is thought to improve division of labor in insect societies. Given the potential benefits of task-related worker differentiation, it is puzzling that physical worker castes, such as soldiers, are extremely rare in social bees and absent in wasps. Following the recent discovery of soldiers in a stingless bee, we studied the occurrence of worker differentiation in 28 stingless bee species from Brazil and found that several species have specialized soldiers for colony defence...
December 2017: Nature Communications
https://www.readbyqxmd.com/read/28232745/gigantea-is-a-co-chaperone-which-facilitates-maturation-of-zeitlupe-in-the-arabidopsis-circadian-clock
#7
Joon-Yung Cha, Jeongsik Kim, Tae-Sung Kim, Qingning Zeng, Lei Wang, Sang Yeol Lee, Woe-Yeon Kim, David E Somers
Circadian clock systems help establish the correct daily phasing of the behavioral, developmental, and molecular events needed for the proper coordination of physiology and metabolism. The circadian oscillator comprises transcription-translation feedback loops but also requires post-translational processes that regulate clock protein homeostasis. GIGANTEA is a unique plant protein involved in the maintenance and control of numerous facets of plant physiology and development. Through an unknown mechanism GIGANTEA stabilizes the F-box protein ZEITLUPE, a key regulator of the circadian clock...
December 2017: Nature Communications
https://www.readbyqxmd.com/read/28550308/fortilin-binds-ire1%C3%AE-and-prevents-er-stress-from-signaling-apoptotic-cell-death
#8
Decha Pinkaew, Abhijnan Chattopadhyay, Matthew D King, Preedakorn Chunhacha, Zhihe Liu, Heather L Stevenson, Yanjie Chen, Patuma Sinthujaroen, Owen M McDougal, Ken Fujise
The endoplasmic reticulum, the cytoplasmic organelle that matures a massive amount of nascent secretory polypeptides, is particularly sensitive to stress. Endoplasmic reticulum stress causes unfolded proteins to populate the organelle, eliciting the unfolded protein response. During the unfolded protein response, GRP78-an endoplasmic reticulum master stress regulator-detaches from three endoplasmic reticulum stress sensors (IRE1α, PERK, and ATF6) and allows them to activate the apoptotic signaling pathway...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548114/virtual-substrate-method-for-nanomaterials-characterization
#9
Bo Da, Jiangwei Liu, Mahito Yamamoto, Yoshihiro Ueda, Kazuyuki Watanabe, Nguyen Thanh Cuong, Songlin Li, Kazuhito Tsukagoshi, Hideki Yoshikawa, Hideo Iwai, Shigeo Tanuma, Hongxuan Guo, Zhaoshun Gao, Xia Sun, Zejun Ding
Characterization techniques available for bulk or thin-film solid-state materials have been extended to substrate-supported nanomaterials, but generally non-quantitatively. This is because the nanomaterial signals are inevitably buried in the signals from the underlying substrate in common reflection-configuration techniques. Here, we propose a virtual substrate method, inspired by the four-point probe technique for resistance measurement as well as the chop-nod method in infrared astronomy, to characterize nanomaterials without the influence of underlying substrate signals from four interrelated measurements...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548109/morphometric-convergence-between-proterozoic-and-post-vegetation-rivers
#10
Alessandro Ielpi, Robert H Rainbird, Dario Ventra, Massimiliano Ghinassi
Proterozoic rivers flowed through barren landscapes, and lacked interactions with macroscopic organisms. It is widely held that, in the absence of vegetation, fluvial systems featured barely entrenched channels that promptly widened over floodplains during floods. This hypothesis has never been tested because of an enduring lack of Precambrian fluvial-channel morphometric data. Here we show, through remote sensing and outcrop sedimentology, that deep rivers were developed in the Proterozoic, and that morphometric parameters for large fluvial channels might have remained within a narrow range over almost 2 billion years...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548104/genomic-analysis-of-oesophageal-squamous-cell-carcinoma-identifies-alcohol-drinking-related-mutation-signature-and-genomic-alterations
#11
Jiang Chang, Wenle Tan, Zhiqiang Ling, Ruibin Xi, Mingming Shao, Mengjie Chen, Yingying Luo, Yanjie Zhao, Yun Liu, Xiancong Huang, Yuchao Xia, Jinlin Hu, Joel S Parker, David Marron, Qionghua Cui, Linna Peng, Jiahui Chu, Hongmin Li, Zhongli Du, Yaling Han, Wen Tan, Zhihua Liu, Qimin Zhan, Yun Li, Weimin Mao, Chen Wu, Dongxin Lin
Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548102/replicating-viral-vector-platform-exploits-alarmin-signals-for-potent-cd8-t-cell-mediated-tumour-immunotherapy
#12
Sandra M Kallert, Stephanie Darbre, Weldy V Bonilla, Mario Kreutzfeldt, Nicolas Page, Philipp Müller, Matthias Kreuzaler, Min Lu, Stéphanie Favre, Florian Kreppel, Max Löhning, Sanjiv A Luther, Alfred Zippelius, Doron Merkler, Daniel D Pinschewer
Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL(eff)) responses. Conversely, the induction of protective tumour-specific CTL(eff) and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548100/hierarchically-structured-lithium-titanate-for-ultrafast-charging-in-long-life-high-capacity-batteries
#13
Mateusz Odziomek, Frédéric Chaput, Anna Rutkowska, Konrad Świerczek, Danuta Olszewska, Maciej Sitarz, Frédéric Lerouge, Stephane Parola
High-performance Li-ion batteries require materials with well-designed and controlled structures on nanometre and micrometre scales. Electrochemical properties can be enhanced by reducing crystallite size and by manipulating structure and morphology. Here we show a method for preparing hierarchically structured Li4Ti5O12 yielding nano- and microstructure well-suited for use in lithium-ion batteries. Scalable glycothermal synthesis yields well-crystallized primary 4-8 nm nanoparticles, assembled into porous secondary particles...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548099/conformational-dynamics-of-dynamin-like-mxa-revealed-by-single-molecule-fret
#14
Yang Chen, Lei Zhang, Laura Graf, Bing Yu, Yue Liu, Georg Kochs, Yongfang Zhao, Song Gao
Human myxovirus resistance protein 1 (MxA) restricts a wide range of viruses and is closely related to the membrane-remodelling GTPase dynamin. The functions of MxA rely on domain rearrangements coupled with GTP hydrolysis cycles. To gain insight into this process, we studied real-time domain dynamics of MxA by single-molecule fluorescence resonance energy transfer. We find that the GTPase domain-bundle-signalling-element (BSE) region can adopt either an 'open' or a 'closed' conformation in all nucleotide-loading conditions...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548098/rationally-designed-mineralization-for-selective-recovery-of-the-rare-earth-elements
#15
Takaaki Hatanaka, Akimasa Matsugami, Takamasa Nonaka, Hideki Takagi, Fumiaki Hayashi, Takao Tani, Nobuhiro Ishida
The increasing demand for rare earth (RE) elements in advanced materials for permanent magnets, rechargeable batteries, catalysts and lamp phosphors necessitates environmentally friendly approaches for their recovery and separation. Here, we propose a mineralization concept for direct extraction of RE ions with Lamp (lanthanide ion mineralization peptide). In aqueous solution containing various metal ions, Lamp promotes the generation of RE hydroxide species with which it binds to form hydrophobic complexes that accumulate spontaneously as insoluble precipitates, even under physiological conditions (pH ∼6...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548097/scalable-focused-ion-beam-creation-of-nearly-lifetime-limited-single-quantum-emitters-in-diamond-nanostructures
#16
Tim Schröder, Matthew E Trusheim, Michael Walsh, Luozhou Li, Jiabao Zheng, Marco Schukraft, Alp Sipahigil, Ruffin E Evans, Denis D Sukachev, Christian T Nguyen, Jose L Pacheco, Ryan M Camacho, Edward S Bielejec, Mikhail D Lukin, Dirk Englund
The controlled creation of defect centre-nanocavity systems is one of the outstanding challenges for efficiently interfacing spin quantum memories with photons for photon-based entanglement operations in a quantum network. Here we demonstrate direct, maskless creation of atom-like single silicon vacancy (SiV) centres in diamond nanostructures via focused ion beam implantation with ∼32 nm lateral precision and <50 nm positioning accuracy relative to a nanocavity. We determine the Si+ ion to SiV centre conversion yield to be ∼2...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548095/metabolic-engineering-of-saccharomyces-cerevisiae-for-production-of-very-long-chain-fatty-acid-derived-chemicals
#17
Tao Yu, Yongjin J Zhou, Leonie Wenning, Quanli Liu, Anastasia Krivoruchko, Verena Siewers, Jens Nielsen, Florian David
Production of chemicals and biofuels through microbial fermentation is an economical and sustainable alternative for traditional chemical synthesis. Here we present the construction of a Saccharomyces cerevisiae platform strain for high-level production of very-long-chain fatty acid (VLCFA)-derived chemicals. Through rewiring the native fatty acid elongation system and implementing a heterologous Mycobacteria FAS I system, we establish an increased biosynthesis of VLCFAs in S. cerevisiae. VLCFAs can be selectively modified towards the fatty alcohol docosanol (C22H46O) by expressing a specific fatty acid reductase...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548094/targeted-recombination-between-homologous-chromosomes-for-precise-breeding-in-tomato
#18
Shdema Filler Hayut, Cathy Melamed Bessudo, Avraham A Levy
Homologous recombination (HR) between parental chromosomes occurs stochastically. Here, we report on targeted recombination between homologous chromosomes upon somatic induction of DNA double-strand breaks (DSBs) via CRISPR-Cas9. We demonstrate this via a visual and molecular assay whereby DSB induction between two alleles carrying different mutations in the PHYTOENE SYNTHASE (PSY1) gene results in yellow fruits with wild type red sectors forming via HR-mediated DSB repair. We also show that in heterozygote plants containing one psy1 allele immune and one sensitive to CRISPR, repair of the broken allele using the unbroken allele sequence template is a common outcome...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548093/all-pure-bipartite-entangled-states-can-be-self-tested
#19
Andrea Coladangelo, Koon Tong Goh, Valerio Scarani
Quantum technologies promise advantages over their classical counterparts in the fields of computation, security and sensing. It is thus desirable that classical users are able to obtain guarantees on quantum devices, even without any knowledge of their inner workings. That such classical certification is possible at all is remarkable: it is a consequence of the violation of Bell inequalities by entangled quantum systems. Device-independent self-testing refers to the most complete such certification: it enables a classical user to uniquely identify the quantum state shared by uncharacterized devices by simply inspecting the correlations of measurement outcomes...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28548092/solid-state-ensemble-of-highly-entangled-photon-sources-at-rubidium-atomic-transitions
#20
Robert Keil, Michael Zopf, Yan Chen, Bianca Höfer, Jiaxiang Zhang, Fei Ding, Oliver G Schmidt
Semiconductor InAs/GaAs quantum dots grown by the Stranski-Krastanov method are among the leading candidates for the deterministic generation of polarization-entangled photon pairs. Despite remarkable progress in the past 20 years, many challenges still remain for this material, such as the extremely low yield, the low degree of entanglement and the large wavelength distribution. Here, we show that with an emerging family of GaAs/AlGaAs quantum dots grown by droplet etching and nanohole infilling, it is possible to obtain a large ensemble of polarization-entangled photon emitters on a wafer without any post-growth tuning...
May 26, 2017: Nature Communications
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