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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/28447668/functional-characterization-of-a-multi-cancer-risk-locus-on-chr5p15-33-reveals-regulation-of-tert-by-znf148
#8
Jun Fang, Jinping Jia, Matthew Makowski, Mai Xu, Zhaoming Wang, Tongwu Zhang, Jason W Hoskins, Jiyeon Choi, Younghun Han, Mingfeng Zhang, Janelle Thomas, Michael Kovacs, Irene Collins, Marta Dzyadyk, Abbey Thompson, Maura O'Neill, Sudipto Das, Qi Lan, Roelof Koster, Rachael S Stolzenberg-Solomon, Peter Kraft, Brian M Wolpin, Pascal W T C Jansen, Sara Olson, Katherine A McGlynn, Peter A Kanetsky, Nilanjan Chatterjee, Jennifer H Barrett, Alison M Dunning, John C Taylor, Julia A Newton-Bishop, D Timothy Bishop, Thorkell Andresson, Gloria M Petersen, Christopher I Amos, Mark M Iles, Katherine L Nathanson, Maria Teresa Landi, Michiel Vermeulen, Kevin M Brown, Laufey T Amundadottir
Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner...
May 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447665/creation-of-energetic-biothermite-inks-using-ferritin-liquid-protein
#9
Joseph M Slocik, Ruel McKenzie, Patrick B Dennis, Rajesh R Naik
Energetic liquids function mainly as fuels due to low energy densities and slow combustion kinetics. Consequently, these properties can be significantly increased through the addition of metal nanomaterials such as aluminium. Unfortunately, nanoparticle additives are restricted to low mass fractions in liquids because of increased viscosities and severe particle agglomeration. Nanoscale protein ionic liquids represent multifunctional solvent systems that are well suited to overcoming low mass fractions of nanoparticles, producing stable nanoparticle dispersions and simultaneously offering a source of oxidizing agents for combustion of reactive nanomaterials...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447620/dna-replication-licensing-factor-cdc6-and-plk4-kinase-antagonistically-regulate-centrosome-duplication-via-sas-6
#10
Xiaowei Xu, Shijiao Huang, Boyan Zhang, Fan Huang, Wangfei Chi, Jingyan Fu, Gang Wang, Si Li, Qing Jiang, Chuanmao Zhang
Centrosome number is tightly controlled during the cell cycle to ensure proper spindle assembly and cell division. However, the underlying mechanism that controls centrosome number remains largely unclear. We show herein that the DNA replication licensing factor Cdc6 is recruited to the proximal side of the centrioles via cyclin A to negatively regulate centrosome duplication by binding and inhibiting the cartwheel protein Sas-6 from forming a stable complex with another centriole duplication core protein, STIL...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447616/high-order-harmonics-measured-by-the-photon-statistics-of-the-infrared-driving-field-exiting-the-atomic-medium
#11
N Tsatrafyllis, I K Kominis, I A Gonoskov, P Tzallas
High-order harmonics in the extreme-ultraviolet spectral range, resulting from the strong-field laser-atom interaction, have been used in a broad range of fascinating applications in all states of matter. In the majority of these studies the harmonic generation process is described using semi-classical theories which treat the electromagnetic field of the driving laser pulse classically without taking into account its quantum nature. In addition, for the measurement of the generated harmonics, all the experiments require diagnostics in the extreme-ultraviolet spectral region...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447614/cell-size-dependent-progression-of-the-cell-cycle-creates-homeostasis-and-flexibility-of-plant-cell-size
#12
Angharad R Jones, Manuel Forero-Vargas, Simon P Withers, Richard S Smith, Jan Traas, Walter Dewitte, James A H Murray
Mean cell size at division is generally constant for specific conditions and cell types, but the mechanisms coupling cell growth and cell cycle control with cell size regulation are poorly understood in intact tissues. Here we show that the continuously dividing fields of cells within the shoot apical meristem of Arabidopsis show dynamic regulation of mean cell size dependent on developmental stage, genotype and environmental signals. We show cell size at division and cell cycle length is effectively predicted using a two-stage cell cycle model linking cell growth and two sequential cyclin dependent kinase (CDK) activities, and experimental results concur in showing that progression through both G1/S and G2/M is size dependent...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447612/distinct-molecular-cues-ensure-a-robust-microtubule-dependent-nuclear-positioning-in-the-drosophila-oocyte
#13
Nicolas Tissot, Jean-Antoine Lepesant, Fred Bernard, Kevin Legent, Floris Bosveld, Charlotte Martin, Orestis Faklaris, Yohanns Bellaïche, Maïté Coppey, Antoine Guichet
Controlling nucleus localization is crucial for a variety of cellular functions. In the Drosophila oocyte, nuclear asymmetric positioning is essential for the reorganization of the microtubule (MT) network that controls the polarized transport of axis determinants. A combination of quantitative three-dimensional live imaging and laser ablation-mediated force analysis reveal that nuclear positioning is ensured with an unexpected level of robustness. We show that the nucleus is pushed to the oocyte antero-dorsal cortex by MTs and that its migration can proceed through distinct tracks...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447610/parp3-is-a-promoter-of-chromosomal-rearrangements-and-limits-g4-dna
#14
Tovah A Day, Jacob V Layer, J Patrick Cleary, Srijoy Guha, Kristen E Stevenson, Trevor Tivey, Sunhee Kim, Anna C Schinzel, Francesca Izzo, John Doench, David E Root, William C Hahn, Brendan D Price, David M Weinstock
Chromosomal rearrangements are essential events in the pathogenesis of both malignant and nonmalignant disorders, yet the factors affecting their formation are incompletely understood. Here we develop a zinc-finger nuclease translocation reporter and screen for factors that modulate rearrangements in human cells. We identify UBC9 and RAD50 as suppressors and 53BP1, DDB1 and poly(ADP)ribose polymerase 3 (PARP3) as promoters of chromosomal rearrangements across human cell types. We focus on PARP3 as it is dispensable for murine viability and has druggable catalytic activity...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447609/spatial-working-memory-alters-the-efficacy-of-input-to-visual-cortex
#15
Yaser Merrikhi, Kelsey Clark, Eddy Albarran, Mohammadbagher Parsa, Marc Zirnsak, Tirin Moore, Behrad Noudoost
Prefrontal cortex modulates sensory signals in extrastriate visual cortex, in part via its direct projections from the frontal eye field (FEF), an area involved in selective attention. We find that working memory-related activity is a dominant signal within FEF input to visual cortex. Although this signal alone does not evoke spiking responses in areas V4 and MT during memory, the gain of visual responses in these areas increases, and neuronal receptive fields expand and shift towards the remembered location, improving the stimulus representation by neuronal populations...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447608/common-variants-in-zmiz1-and-near-ngf-confer-risk-for-primary-dysmenorrhoea
#16
Zhiqiang Li, Jianhua Chen, Ying Zhao, Yujiong Wang, Jinrui Xu, Jue Ji, Jingyi Shen, Weiping Zhang, Zuosong Chen, Qilin Sun, Lijuan Mao, Shulin Cheng, Bo Yang, Dongtao Zhang, Yufeng Xu, Yingying Zhao, Danping Liu, Yinhuan Shen, Weijie Zhang, Changgui Li, Jiawei Shen, Yongyong Shi
Primary dysmenorrhoea, defined as painful menstrual cramps in the absence of pelvic pathology, is a common problem in women of reproductive age. Its aetiology and pathophysiology remain largely unknown. Here we performed a two-stage genome-wide association study and subsequent replication study to identify genetic factors associated with primary dysmenorrhoea in a total of 6,770 Chinese individuals. Our analysis provided evidence of a significant (P<5 × 10(-8)) association at rs76518691 in the gene ZMIZ1 and at rs7523831 near NGF...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447604/wearable-smart-sensor-systems-integrated-on-soft-contact-lenses-for-wireless-ocular-diagnostics
#17
Joohee Kim, Minji Kim, Mi-Sun Lee, Kukjoo Kim, Sangyoon Ji, Yun-Tae Kim, Jihun Park, Kyungmin Na, Kwi-Hyun Bae, Hong Kyun Kim, Franklin Bien, Chang Young Lee, Jang-Ung Park
Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447603/efficient-self-emulsification-via-cooling-heating-cycles
#18
Slavka Tcholakova, Zhulieta Valkova, Diana Cholakova, Zahari Vinarov, Ivan Lesov, Nikolai Denkov, Stoyan K Smoukov
In self-emulsification higher-energy micrometre and sub-micrometre oil droplets are spontaneously produced from larger ones and only a few such methods are known. They usually involve a one-time reduction in oil solubility in the continuous medium via changing temperature or solvents or a phase inversion in which the preferred curvature of the interfacial surfactant layer changes its sign. Here we harness narrow-range temperature cycling to cause repeated breakup of droplets to higher-energy states. We describe three drop breakup mechanisms that lead the drops to burst spontaneously into thousands of smaller droplets...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447602/spatial-computation-of-intratumoral-t-cells-correlates-with-survival-of-patients-with-pancreatic-cancer
#19
Julienne L Carstens, Pedro Correa de Sampaio, Dalu Yang, Souptik Barua, Huamin Wang, Arvind Rao, James P Allison, Valerie S LeBleu, Raghu Kalluri
The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28446752/near-atomic-structure-of-japanese-encephalitis-virus-reveals-critical-determinants-of-virulence-and-stability
#20
Xiangxi Wang, Shi-Hua Li, Ling Zhu, Qing-Gong Nian, Shuai Yuan, Qiang Gao, Zhongyu Hu, Qing Ye, Xiao-Feng Li, Dong-Yang Xie, Neil Shaw, Junzhi Wang, Thomas S Walter, Juha T Huiskonen, Elizabeth E Fry, Cheng-Feng Qin, David I Stuart, Zihe Rao
Although several different flaviviruses may cause encephalitis, Japanese encephalitis virus is the most significant, being responsible for thousands of deaths each year in Asia. The structural and molecular basis of this encephalitis is not fully understood. Here, we report the cryo-electron microscopy structure of mature Japanese encephalitis virus at near-atomic resolution, which reveals an unusual "hole" on the surface, surrounded by five encephalitic-specific motifs implicated in receptor binding. Glu138 of E, which is highly conserved in encephalitic flaviviruses, maps onto one of these motifs and is essential for binding to neuroblastoma cells, with the E138K mutation abrogating the neurovirulence and neuroinvasiveness of Japanese encephalitis virus in mice...
April 26, 2017: Nature Communications
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