journal
MENU ▼
Read by QxMD icon Read
search

Nature Communications

journal
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/28345670/domain-dependent-effects-of-insulin-and-igf-1-receptors-on-signalling-and-gene-expression
#8
Weikang Cai, Masaji Sakaguchi, Andre Kleinridders, Gonzalo Gonzalez-Del Pino, Jonathan M Dreyfuss, Brian T O'Neill, Alfred K Ramirez, Hui Pan, Jonathon N Winnay, Jeremie Boucher, Michael J Eck, C Ronald Kahn
Despite a high degree of homology, insulin receptor (IR) and IGF-1 receptor (IGF1R) mediate distinct cellular and physiological functions. Here, we demonstrate how domain differences between IR and IGF1R contribute to the distinct functions of these receptors using chimeric and site-mutated receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to their higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345669/a-coupled-human-earth-model-perspective-on-long-term-trends-in-the-global-marine-fishery
#9
E D Galbraith, D A Carozza, D Bianchi
The global wild marine fish harvest increased fourfold between 1950 and a peak value near the end of the 20th century, reflecting interactions between anthropogenic and ecological forces. Here, we examine these interactions in a bio-energetically constrained, spatially and temporally resolved model of global fisheries. We conduct historical hindcasts with the model, which suggest that technological progress can explain most of the 20th century increase of fish harvest. In contrast, projections extending this rate of technological progress into the future under open access suggest a long-term decrease in harvest due to over-fishing...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345656/structure-and-function-of-the-zika-virus-full-length-ns5-protein
#10
Baoyu Zhao, Guanghui Yi, Fenglei Du, Yin-Chih Chuang, Robert C Vaughan, Banumathi Sankaran, C Cheng Kao, Pingwei Li
The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345654/the-soybean-gmsnap18-gene-underlies-two-types-of-resistance-to-soybean-cyst-nematode
#11
Shiming Liu, Pramod K Kandoth, Naoufal Lakhssassi, Jingwen Kang, Vincent Colantonio, Robert Heinz, Greg Yeckel, Zhou Zhou, Sadia Bekal, Johannes Dapprich, Bjorn Rotter, Silvia Cianzio, Melissa G Mitchum, Khalid Meksem
Two types of resistant soybean (Glycine max (L.) Merr.) sources are widely used against soybean cyst nematode (SCN, Heterodera glycines Ichinohe). These include Peking-type soybean, whose resistance requires both the rhg1-a and Rhg4 alleles, and PI 88788-type soybean, whose resistance requires only the rhg1-b allele. Multiple copy number of PI 88788-type GmSNAP18, GmAAT, and GmWI12 in one genomic segment simultaneously contribute to rhg1-b resistance. Using an integrated set of genetic and genomic approaches, we demonstrate that the rhg1-a Peking-type GmSNAP18 is sufficient for resistance to SCN in combination with Rhg4...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345650/rational-combination-of-oncolytic-vaccinia-virus-and-pd-l1-blockade-works-synergistically-to-enhance-therapeutic-efficacy
#12
Zuqiang Liu, Roshni Ravindranathan, Pawel Kalinski, Z Sheng Guo, David L Bartlett
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345600/the-structure-of-zika-virus-ns5-reveals-a-conserved-domain-conformation
#13
Boxiao Wang, Xiao-Feng Tan, Stephanie Thurmond, Zhi-Min Zhang, Asher Lin, Rong Hai, Jikui Song
The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345596/crystal-structure-of-zika-virus-ns5-rna-dependent-rna-polymerase
#14
Andre S Godoy, Gustavo M A Lima, Ketllyn I Z Oliveira, Naiara U Torres, Fernando V Maluf, Rafael V C Guido, Glaucius Oliva
The current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel efficacious and safe antiviral drugs. Due to its central role in RNA viral replication, the non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is a prime target for drug discovery. Here we describe the crystal structure of the recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as a platform for structure-based drug design strategy...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345588/macrophages-induce-akt-%C3%AE-catenin-dependent-lgr5-stem-cell-activation-and-hair-follicle-regeneration-through-tnf
#15
Xusheng Wang, Haiyan Chen, Ruiyun Tian, Yiling Zhang, Marina S Drutskaya, Chengmei Wang, Jianfeng Ge, Zhimeng Fan, Deqiang Kong, Xiaoxiao Wang, Ting Cai, Ying Zhou, Jingwen Wang, Jinmei Wang, Shan Wang, Zhihai Qin, Huanhuan Jia, Yue Wu, Jia Liu, Sergei A Nedospasov, Edward E Tredget, Mei Lin, Jianjun Liu, Yuyang Jiang, Yaojiong Wu
Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen-anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345585/direct-amidation-of-esters-with-nitroarenes
#16
Chi Wai Cheung, Marten Leendert Ploeger, Xile Hu
Esters are one of the most common functional groups in natural and synthetic products, and the one-step conversion of the ester group into other functional groups is an attractive strategy in organic synthesis. Direct amidation of esters is particularly appealing due to the omnipresence of the amide moiety in biomolecules, fine chemicals, and drug candidates. However, efficient methods for direct amidation of unactivated esters are still lacking. Here we report nickel-catalysed reductive coupling of unactivated esters with nitroarenes to furnish in one step a wide range of amides bearing functional groups relevant to the development of drugs and agrochemicals...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345584/terahertz-and-mid-infrared-plasmons-in-three-dimensional-nanoporous-graphene
#17
Fausto D'Apuzzo, Alba R Piacenti, Flavio Giorgianni, Marta Autore, Mariangela Cestelli Guidi, Augusto Marcelli, Ulrich Schade, Yoshikazu Ito, Mingwei Chen, Stefano Lupi
Two-dimensional (2D) graphene emerged as an outstanding material for plasmonic and photonic applications due to its charge-density tunability, high electron mobility, optical transparency and mechanical flexibility. Recently, novel fabrication processes have realised a three-dimensional (3D) nanoporous configuration of high-quality monolayer graphene which provides a third dimension to this material. In this work, we investigate the optical behaviour of nanoporous graphene by means of terahertz and infrared spectroscopy...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345582/enhancing-titres-of-therapeutic-viral-vectors-using-the-transgene-repression-in-vector-production-trip-system
#18
H E Maunder, J Wright, B R Kolli, C R Vieira, T T Mkandawire, S Tatoris, V Kennedy, S Iqball, G Devarajan, S Ellis, Y Lad, N G Clarkson, K A Mitrophanous, D C Farley
A key challenge in the field of therapeutic viral vector/vaccine manufacturing is maximizing production. For most vector platforms, the 'benchmark' vector titres are achieved with inert reporter genes. However, expression of therapeutic transgenes can often adversely affect vector titres due to biological effects on cell metabolism and/or on the vector virion itself. Here, we exemplify the novel 'Transgene Repression In vector Production' (TRiP) system for the production of both RNA- and DNA-based viral vectors...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345579/inhibition-of-delta-secretase-improves-cognitive-functions-in-mouse-models-of-alzheimer-s-disease
#19
Zhentao Zhang, Obiamaka Obianyo, Elfriede Dall, Yuhong Du, Haian Fu, Xia Liu, Seong Su Kang, Mingke Song, Shan-Ping Yu, Chiara Cabrele, Mario Schubert, Xiaoguang Li, Jian-Zhi Wang, Hans Brandstetter, Keqiang Ye
δ-secretase, also known as asparagine endopeptidase (AEP) or legumain, is a lysosomal cysteine protease that cleaves both amyloid precursor protein (APP) and tau, mediating the amyloid-β and tau pathology in Alzheimer's disease (AD). Here we report the therapeutic effect of an orally bioactive and brain permeable δ-secretase inhibitor in mouse models of AD. We performed a high-throughput screen and identified a non-toxic and selective δ-secretase inhibitor, termed compound 11, that specifically blocks δ-secretase but not other related cysteine proteases...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28337990/lateral-orbitofrontal-cortex-anticipates-choices-and-integrates-prior-with-current-information
#20
Ramon Nogueira, Juan M Abolafia, Jan Drugowitsch, Emili Balaguer-Ballester, Maria V Sanchez-Vives, Rubén Moreno-Bote
Adaptive behavior requires integrating prior with current information to anticipate upcoming events. Brain structures related to this computation should bring relevant signals from the recent past into the present. Here we report that rats can integrate the most recent prior information with sensory information, thereby improving behavior on a perceptual decision-making task with outcome-dependent past trial history. We find that anticipatory signals in the orbitofrontal cortex about upcoming choice increase over time and are even present before stimulus onset...
March 24, 2017: Nature Communications
journal
journal
42959
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"