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Nature Communications

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https://www.readbyqxmd.com/read/30413720/leveraging-heterogeneity-across-multiple-datasets-increases-cell-mixture-deconvolution-accuracy-and-reduces-biological-and-technical-biases
#1
Francesco Vallania, Andrew Tam, Shane Lofgren, Steven Schaffert, Tej D Azad, Erika Bongen, Winston Haynes, Meia Alsup, Michael Alonso, Mark Davis, Edgar Engleman, Purvesh Khatri
In silico quantification of cell proportions from mixed-cell transcriptomics data (deconvolution) requires a reference expression matrix, called basis matrix. We hypothesize that matrices created using only healthy samples from a single microarray platform would introduce biological and technical biases in deconvolution. We show presence of such biases in two existing matrices, IRIS and LM22, irrespective of deconvolution method. Here, we present immunoStates, a basis matrix built using 6160 samples with different disease states across 42 microarray platforms...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413719/crystallographic-and-spectroscopic-assignment-of-the-proton-transfer-pathway-in-fefe-hydrogenases
#2
Jifu Duan, Moritz Senger, Julian Esselborn, Vera Engelbrecht, Florian Wittkamp, Ulf-Peter Apfel, Eckhard Hofmann, Sven T Stripp, Thomas Happe, Martin Winkler
The unmatched catalytic turnover rates of [FeFe]-hydrogenases require an exceptionally efficient proton-transfer (PT) pathway to shuttle protons as substrates or products between bulk water and catalytic center. For clostridial [FeFe]-hydrogenase CpI such a pathway has been proposed and analyzed, but mainly on a theoretical basis. Here, eleven enzyme variants of two different [FeFe]-hydrogenases (CpI and HydA1) with substitutions in the presumptive PT-pathway are examined kinetically, spectroscopically, and crystallographically to provide solid experimental proof for its role in hydrogen-turnover...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413718/targeting-17q23-amplicon-to-overcome-the-resistance-to-anti-her2-therapy-in-her2-breast-cancer
#3
Yunhua Liu, Jiangsheng Xu, Hyun Ho Choi, Cecil Han, Yuanzhang Fang, Yujing Li, Kevin Van der Jeught, Hanchen Xu, Lu Zhang, Michael Frieden, Lifei Wang, Haniyeh Eyvani, Yifan Sun, Gang Zhao, Yuntian Zhang, Sheng Liu, Jun Wan, Cheng Huang, Guang Ji, Xiongbin Lu, Xiaoming He, Xinna Zhang
Chromosome 17q23 amplification occurs in ~11% of human breast cancers. Enriched in HER2+ breast cancers, the 17q23 amplification is significantly correlated with poor clinical outcomes. In addition to the previously identified oncogene WIP1, we uncover an oncogenic microRNA gene, MIR21, in a majority of the WIP1-containing 17q23 amplicons. The 17q23 amplification results in aberrant expression of WIP1 and miR-21, which not only promotes breast tumorigenesis, but also leads to resistance to anti-HER2 therapies...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413717/spontaneous-formation-of-nanoparticles-on-electrospun-nanofibres
#4
Norbert Radacsi, Fernando Diaz Campos, Calum R I Chisholm, Konstantinos P Giapis
We report the spontaneous formation of nanoparticles on smooth nanofibres in a single-step electrospinning process, as an inexpensive and scalable method for producing high-surface-area composites. Layers of nanofibres, containing the proton conducting electrolyte, caesium dihydrogen phosphate, are deposited uniformly over large area substrates from clear solutions of the electrolyte mixed with polymers. Under certain conditions, the normally smooth nanofibres develop caesium dihydrogen phosphate nanoparticles in large numbers on their external surface...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413716/harnessing-photoinduced-electron-transfer-to-optically-determine-protein-sub-nanoscale-atomic-distances
#5
Antonios Pantazis, Karin Westerberg, Thorsten Althoff, Jeff Abramson, Riccardo Olcese
Proteins possess a complex and dynamic structure, which is influenced by external signals and may change as they perform their biological functions. We present an optical approach, distance-encoding photoinduced electron transfer (DEPET), capable of the simultaneous study of protein structure and function. An alternative to FRET-based methods, DEPET is based on the quenching of small conjugated fluorophores by photoinduced electron transfer: a reaction that requires contact of the excited fluorophore with a suitable electron donor...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413715/discovery-of-rare-cells-from-voluminous-single-cell-expression-data
#6
Aashi Jindal, Prashant Gupta, Jayadeva, Debarka Sengupta
Single cell messenger RNA sequencing (scRNA-seq) provides a window into transcriptional landscapes in complex tissues. The recent introduction of droplet based transcriptomics platforms has enabled the parallel screening of thousands of cells. Large-scale single cell transcriptomics is advantageous as it promises the discovery of a number of rare cell sub-populations. Existing algorithms to find rare cells scale unbearably slowly or terminate, as the sample size grows to the order of tens of thousands. We propose Finder of Rare Entities (FiRE), an algorithm that, in a matter of seconds, assigns a rareness score to every individual expression profile under study...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413714/inflammation-induced-id2-promotes-plasticity-in-regulatory-t-cells
#7
Sung-Min Hwang, Garima Sharma, Ravi Verma, Seohyun Byun, Dipayan Rudra, Sin-Hyeog Im
TH 17 cells originating from regulatory T (Treg ) cells upon loss of the Treg- specific transcription factor Foxp3 accumulate in sites of inflammation and aggravate autoimmune diseases. Whether an active mechanism drives the generation of these pathogenic 'ex-Foxp3 TH 17' cells, remains unclear. Here we show that pro-inflammatory cytokines enhance the expression of transcription regulator Id2, which mediates cellular plasticity of Treg into ex-Foxp3 TH 17 cells. Expression of Id2 in in vitro differentiated iTreg cells reduces the expression of Foxp3 by sequestration of the transcription activator E2A, leading to the induction of TH 17-related cytokines...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413713/design-and-22-step-synthesis-of-highly-potent-d-ring-modified-and-linker-equipped-analogs-of-spongistatin-1
#8
Linda M Suen, Makeda A Tekle-Smith, Kevin S Williamson, Joshua R Infantine, Samuel K Reznik, Paul S Tanis, Tyler D Casselman, Dan L Sackett, James L Leighton
Spongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody-drug conjugates and other targeted delivery approaches. Unfortunately, it is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive. As a result, the design and synthesis of more acid-stable and linker functional group-equipped analogs that retain the low picomolar potency of the parent natural product requires more efficient and step-economical synthetic access...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413712/the-diamine-cation-is-not-a-chemical-example-where-density-functional-theory-fails
#9
LETTER
Zulfikhar A Ali, Fredy W Aquino, Bryan M Wong
No abstract text is available yet for this article.
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413711/a-common-genetic-mechanism-underlies-morphological-diversity-in-fruits-and-other-plant-organs
#10
Shan Wu, Biyao Zhang, Neda Keyhaninejad, Gustavo R Rodríguez, Hyun Jung Kim, Manohar Chakrabarti, Eudald Illa-Berenguer, Nathan K Taitano, M J Gonzalo, Aurora Díaz, Yupeng Pan, Courtney P Leisner, Dennis Halterman, C Robin Buell, Yiqun Weng, Shelley H Jansky, Herman van Eck, Johan Willemsen, Antonio J Monforte, Tea Meulia, Esther van der Knaap
Shapes of edible plant organs vary dramatically among and within crop plants. To explain and ultimately employ this variation towards crop improvement, we determined the genetic, molecular and cellular bases of fruit shape diversity in tomato. Through positional cloning, protein interaction studies, and genome editing, we report that OVATE Family Proteins and TONNEAU1 Recruiting Motif proteins regulate cell division patterns in ovary development to alter final fruit shape. The physical interactions between the members of these two families are necessary for dynamic relocalization of the protein complexes to different cellular compartments when expressed in tobacco leaf cells...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413710/mapping-knowledge-gaps-in-marine-diversity-reveals-a-latitudinal-gradient-of-missing-species-richness
#11
André Menegotto, Thiago F Rangel
A reliable description of any spatial pattern in species richness requires accurate knowledge about species geographical distribution. However, sampling bias may generate artefactual absences within species range and compromise our capacity to describe biodiversity patterns. Here, we analysed the spatial distribution of 35,000 marine species (varying from copepods to sharks) to identify missing occurrences (gaps) across their latitudinal range. We find a latitudinal gradient of species absence peaking near the equator, a pattern observed in both shallow and deep waters...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413709/crystal-structures-of-human-et-b-receptor-provide-mechanistic-insight-into-receptor-activation-and-partial-activation
#12
Wataru Shihoya, Tamaki Izume, Asuka Inoue, Keitaro Yamashita, Francois Marie Ngako Kadji, Kunio Hirata, Junken Aoki, Tomohiro Nishizawa, Osamu Nureki
Endothelin receptors (ETA and ETB ) are class A GPCRs activated by vasoactive peptide endothelins, and are involved in blood pressure regulation. ETB -selective signalling induces vasorelaxation, and thus selective ETB agonists are expected to be utilized for improved anti-tumour drug delivery and neuroprotection. Here, we report the crystal structures of human ETB receptor in complex with ETB -selective agonist, endothelin-3 and an ETB -selective endothelin analogue IRL1620. The structure of the endothelin-3-bound receptor reveals that the disruption of water-mediated interactions between W6...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413708/a-gas-breathing-hydrogen-air-biofuel-cell-comprising-a-redox-polymer-hydrogenase-based-bioanode
#13
Julian Szczesny, Nikola Marković, Felipe Conzuelo, Sónia Zacarias, Inês A C Pereira, Wolfgang Lubitz, Nicolas Plumeré, Wolfgang Schuhmann, Adrian Ruff
Hydrogen is one of the most promising alternatives for fossil fuels. However, the power output of hydrogen/oxygen fuel cells is often restricted by mass transport limitations of the substrate. Here, we present a dual-gas breathing H2 /air biofuel cell that overcomes these limitations. The cell is equipped with a hydrogen-oxidizing redox polymer/hydrogenase gas-breathing bioanode and an oxygen-reducing bilirubin oxidase gas-breathing biocathode (operated in a direct electron transfer regime). The bioanode consists of a two layer system with a redox polymer-based adhesion layer and an active, redox polymer/hydrogenase top layer...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413707/diet-induced-adaptive-thermogenesis-requires-neuropeptide-ff-receptor-2-signalling
#14
Lei Zhang, Chi Kin Ip, I-Chieh J Lee, Yue Qi, Felicia Reed, Tim Karl, Jac Kee Low, Ronaldo F Enriquez, Nicola J Lee, Paul A Baldock, Herbert Herzog
Excess caloric intake results in increased fat accumulation and an increase in energy expenditure via diet-induced adaptive thermogenesis; however, the underlying mechanisms controlling these processes are unclear. Here we identify the neuropeptide FF receptor-2 (NPFFR2) as a critical regulator of diet-induced thermogenesis and bone homoeostasis. Npffr2-/- mice exhibit a stronger bone phenotype and when fed a HFD display exacerbated obesity associated with a failure in activating brown adipose tissue (BAT) thermogenic response to energy excess, whereas the activation of cold-induced BAT thermogenesis is unaffected...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413706/the-critical-role-of-ampk-in-driving-akt-activation-under-stress-tumorigenesis-and-drug-resistance
#15
Fei Han, Chien-Feng Li, Zhen Cai, Xian Zhang, Guoxiang Jin, Wei-Na Zhang, Chuan Xu, Chi-Yun Wang, John Morrow, Shuxing Zhang, Dazhi Xu, Guihua Wang, Hui-Kuan Lin
PI3K/Akt signaling is activated in cancers and governs tumor initiation and progression, but how Akt is activated under diverse stresses is poorly understood. Here we identify AMPK as an essential regulator for Akt activation by various stresses. Surprisingly, AMPK is also activated by growth factor EGF through Ca2+/Calmodulin-dependent kinase and is essential for EGF-mediated Akt activation and biological functions. AMPK phosphorylates Skp2 at S256 and promotes the integrity and E3 ligase activity of Skp2 SCF complex leading to K63-linked ubiquitination and activation of Akt and subsequent oncogenic processes...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413705/oestrogen-receptor-%C3%AE-af-1-and-af-2-domains-have-cell-population-specific-functions-in-the-mammary-epithelium
#16
Stéphanie Cagnet, Dalya Ataca, George Sflomos, Patrick Aouad, Sonia Schuepbach-Mallepell, Henry Hugues, Andrée Krust, Ayyakkannu Ayyanan, Valentina Scabia, Cathrin Brisken
Oestrogen receptor α (ERα) is a transcription factor with ligand-independent and ligand-dependent activation functions (AF)-1 and -2. Oestrogens control postnatal mammary gland development acting on a subset of mammary epithelial cells (MECs), termed sensor cells, which are ERα-positive by immunohistochemistry (IHC) and secrete paracrine factors, which stimulate ERα-negative responder cells. Here we show that deletion of AF-1 or AF-2 blocks pubertal ductal growth and subsequent development because both are required for expression of essential paracrine mediators...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413704/neodymium-isotope-evidence-for-glacial-interglacial-variability-of-deepwater-transit-time-in-the-pacific-ocean
#17
Rong Hu, Alexander M Piotrowski
There is evidence for greater carbon storage in the glacial deep Pacific, but it is uncertain whether it was caused by changes in ventilation, circulation, and biological productivity. The spatial εNd evolution in the deep Pacific provides information on the deepwater transit time. Seven new foraminiferal εNd records are presented to systematically constrain glacial to interglacial changes in deep Pacific overturning and two different εNd evolution regimes occur spatially in the Pacific with reduced meridional εNd gradients in glacials, suggesting a faster deep Pacific overturning circulation...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413703/transcriptome-wide-identification-of-transient-rna-g-quadruplexes-in-human-cells
#18
Sunny Y Yang, Pauline Lejault, Sandy Chevrier, Romain Boidot, A Gordon Robertson, Judy M Y Wong, David Monchaud
Guanine-rich RNA sequences can fold into four-stranded structures, termed G-quadruplexes (G4-RNAs), whose biological roles are poorly understood, and in vivo existence is debated. To profile biologically relevant G4-RNA in the human transcriptome, we report here on G4RP-seq, which combines G4-RNA-specific precipitation (G4RP) with sequencing. This protocol comprises a chemical crosslinking step, followed by affinity capture with the G4-specific small-molecule ligand/probe BioTASQ, and target identification by sequencing, allowing for capturing global snapshots of transiently folded G4-RNAs...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413702/chemical-bonding-origin-of-the-unexpected-isotropic-physical-properties-in-thermoelectric-mg-3-sb-2-and-related-materials
#19
Jiawei Zhang, Lirong Song, Mattia Sist, Kasper Tolborg, Bo Brummerstedt Iversen
The Mg3 Sb2 structure is currently being intensely scrutinized due to its outstanding thermoelectric properties. Usually, it is described as a layered Zintl phase with a clear distinction between covalent [Mg2 Sb2 ]2- layers and ionic Mg2+ layers. Based on the quantitative chemical bonding analysis, we unravel instead that Mg3 Sb2 exhibits a nearly isotropic three-dimensional bonding network with the interlayer and intralayer bonds being mostly ionic and surprisingly similar, which results in the nearly isotropic structural and thermal properties...
November 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/30413701/plant-defences-mediate-interactions-between-herbivory-and-the-direct-foliar-uptake-of-atmospheric-reactive-nitrogen
#20
Stuart A Campbell, Dena M Vallano
Reactive nitrogen from human sources (e.g., nitrogen dioxide, NO2 ) is taken up by plant roots following deposition to soils, but can also be assimilated by leaves directly from the atmosphere. Leaf uptake should alter plant metabolism and overall nitrogen balance and indirectly influence plant consumers; however, these consequences remain poorly understood. Here we show that direct foliar assimilation of NO2 increases levels of nitrogen-based defensive metabolites in leaves and reduces herbivore consumption and growth...
November 9, 2018: Nature Communications
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