Thursday, November 30, 2017

Nature Communications -30 November 2017

 
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30 November 2017 
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The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their pioneering work in Drosophila that elucidated the molecular mechanisms controlling circadian rhythm.
 
 
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Directing intracellular supramolecular assembly with N-heteroaromatic quaterthiophene analogues OPEN
David Y. W. Ng, Roman Vill, Yuzhou Wu, Kaloian Koynov, Yu Tokura, Weina Liu, Susanne Sihler, Andreas Kreyes, Sandra Ritz, Holger Barth, Ulrich Ziener & Tanja Weil

Self-assembly of synthetic molecules in living cells can influence cell function, but is extremely challenging due to the complex environment of cells. Here the authors report the self-assembly of small organic molecules that locate, target and self-report their supramolecular behavior in living cells.

29 November 2017 | doi: 10.1038/s41467-017-02020-2
Molecular self-assembly  Self-assembly  Structural properties 

Intracellular localization of nanoparticle dimers by chirality reversal OPEN
Maozhong Sun, Liguang Xu, Joong Hwan Banhg, Hua Kuang, Silas Alben, Nicholas A. Kotov & Chuanlai Xu

The ability to spectroscopically pinpoint whether nanoparticles are located inside or outside of cells represents an overarching need in biology and medicine. Here, the authors show that the chirality of DNA-bridged particle dimers reverses when they cross the cell membrane, providing a real-time chiroptical signature of their intra- or extracellular location.

29 November 2017 | doi: 10.1038/s41467-017-01337-2
Cell–particle interactions  Circular dichroism  Nanobiotechnology  Nanoparticles 

Giant barocaloric effects over a wide temperature range in superionic conductor AgI OPEN
Araceli Aznar, Pol Lloveras, Michela Romanini, María Barrio, Josep-Lluís Tamarit, Claudio Cazorla, Daniel Errandonea, Neil D. Mathur, Antoni Planes, Xavier Moya & Lluís Mañosa

Barocaloric materials offer promise in solid-state cooling devices, but few materials have been show to display giant barocaloric effects near room temperature. Here, the authors demonstrate that solid electrolyte AgI displays giant inverse barocaloric effects near its superionic phase transition at ~420 K.

29 November 2017 | doi: 10.1038/s41467-017-01898-2
Materials chemistry  Materials for energy and catalysis  Phase transitions and critical phenomena 

Low-threshold optically pumped lasing in highly strained germanium nanowires OPEN
Shuyu Bao, Daeik Kim, Chibuzo Onwukaeme, Shashank Gupta, Krishna Saraswat, Kwang Hong Lee, Yeji Kim, Dabin Min, Yongduck Jung, Haodong Qiu, Hong Wang, Eugene A. Fitzgerald, Chuan Seng Tan & Donguk Nam

Integrating group IV lasing devices into technologically relevant CMOS architectures has proven challenging. Here, the authors demonstrate low-threshold lasing, which is important for potential electronic and photonic circuits, using strained germanium nanowires as the gain material.

29 November 2017 | doi: 10.1038/s41467-017-02026-w
Semiconductor lasers  Silicon photonics 

Scaling relationships and theory for vibrational frequencies of adsorbates on transition metal surfaces OPEN
Joshua L. Lansford, Alexander V. Mironenko & Dionisios G. Vlachos

Vibrational excitations are a fingerprint of molecule–surface interactions, but knowing how they scale across materials is tricky. Here, the authors discover correlations between the vibrational frequencies of adsorbates on transition metals, developing a predictive theory to allow interpretation of complex experimental spectra.

29 November 2017 | doi: 10.1038/s41467-017-01983-6
Chemical physics  Heterogeneous catalysis  Surface spectroscopy 

Bacterial endosymbionts influence host sexuality and reveal reproductive genes of early divergent fungi OPEN
Stephen J. Mondo, Olga A. Lastovetsky, Maria L. Gaspar, Nicole H. Schwardt, Colin C. Barber, Robert Riley, Hui Sun, Igor V. Grigoriev & Teresa E. Pawlowska

Cells of the fungus Rhizopus microsporus contain Burkholderia endobacteria that control its asexual reproduction. Here, the authors show that the endobacteria also mediate mating of the fungal host by modulating expression of a GTPase central to fungal reproductive development.

29 November 2017 | doi: 10.1038/s41467-017-02052-8
Coevolution  Fungal evolution 

Hourglass Dirac chain metal in rhenium dioxide OPEN
Shan-Shan Wang, Ying Liu, Zhi-Ming Yu, Xian-Lei Sheng & Shengyuan A. Yang

Exotic topological particles are reported to arise from special types of symmetry protection. Here, Wang et al. predict an hourglass Dirac chain metal protected by nonsymmorphic symmetries and its possible realization in ReO2.

29 November 2017 | doi: 10.1038/s41467-017-01986-3
Electronic properties and materials  Electronic structure  Topological insulators 

Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading OPEN
Ido Goldstein, Ville Paakinaho, Songjoon Baek, Myong-Hee Sung & Gordon L. Hager

The cytokines IL-1β and IL-6 mediate the systemic acute phase response (APR). Here, the authors provide evidence that these cytokines lead to both synergistic and antagonistic gene expression during APR; synergistic induction occurs by assisted loading of STAT3 on chromatin by NF-κB.

29 November 2017 | doi: 10.1038/s41467-017-02055-5
Acute inflammation  Gene regulation in immune cells  Transcription 

Notch transactivates Rheb to maintain the multipotency of TSC-null cells OPEN
Jun-Hung Cho, Bhaumik Patel, Santosh Bonala, Sasikanth Manne, Yan Zhou, Surya K. Vadrevu, Jalpa Patel, Marco Peronaci, Shanawaz Ghouse, Elizabeth P. Henske, Fabrice Roegiers, Krinio Giannikou, David J. Kwiatkowski, Hossein Mansouri, Maciej M. Markiewski, Brandon White & Magdalena Karbowniczek

Tuberous sclerosis complex (TSC) is a rare genetic condition causing tumours with differentiation abnormalities; however the molecular mechanisms causing these defects are unclear. Here the authors show that Notch cooperates with Rheb to block cell differentiation forming a regulatory loop that could underlie TSC tumorigenesis.

29 November 2017 | doi: 10.1038/s41467-017-01845-1
Cancer  Tumour-suppressor proteins 

Metal-hydrogen systems with an exceptionally large and tunable thermodynamic destabilization OPEN
Peter Ngene, Alessandro Longo, Lennard Mooij, Wim Bras & Bernard Dam

Tailoring the thermodynamics of metal-hydrogen interactions is crucial for tuning the properties of metal hydrides but remains difficult to control. Here, the authors create an yttrium hydrogen sensor sensitive to pressure changes of up to four orders of magnitude by adding zirconium into the Y lattice.

29 November 2017 | doi: 10.1038/s41467-017-02043-9
Hydrogen storage materials  Materials for energy and catalysis  Structural properties 

Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer OPEN
Jingsong Zhang, Jessica J. Cunningham, Joel S. Brown & Robert A. Gatenby

Evolution of resistance is a common cause of cancer treatment failure and tumor progression. Here, the authors present a method for integrating evolutionary principles based on adaptive therapy into abiraterone therapy for metastatic castrate-resistant prostate cancer and show the positive results of an interim analysis of a trial cohort.

28 November 2017 | doi: 10.1038/s41467-017-01968-5
Cancer therapeutic resistance  Experimental evolution 

Dissipative quantum error correction and application to quantum sensing with trapped ions OPEN
F. Reiter, A. S. Sørensen, P. Zoller & C. A. Muschik

Quantum error correction plays a key role in quantum information and metrology, but generally requires complex gates and measurements sequences. Here, the authors use trapped ions to implement a scheme in which always-on coupling to an engineered environment protects the qubit against errors.

28 November 2017 | doi: 10.1038/s41467-017-01895-5
Quantum metrology  Quantum optics 

Parkin targets HIF-1α for ubiquitination and degradation to inhibit breast tumor progression OPEN
Juan Liu, Cen Zhang, Yuhan Zhao, Xuetian Yue, Hao Wu, Shan Huang, James Chen, Kyle Tomsky, Haiyang Xie, Christen A. Khella, Michael L. Gatza, Dajing Xia, Jimin Gao, Eileen White, Bruce G. Haffty, Wenwei Hu & Zhaohui Feng

Parkin is an E3 ubiquitin ligase involved in Parkinson’s disease. Parkin has also been linked to cancer suppression but the mechanisms are unclear. Here the authors show that Parkin regulates HIF-1α through ubiquitin-dependent degradation, thus inhibiting metastasis of breast cancer cells.

28 November 2017 | doi: 10.1038/s41467-017-01947-w
Tumour-suppressor proteins  Ubiquitylation 

Centromere evolution and CpG methylation during vertebrate speciation OPEN
Kazuki Ichikawa, Shingo Tomioka, Yuta Suzuki, Ryohei Nakamura, Koichiro Doi, Jun Yoshimura, Masahiko Kumagai, Yusuke Inoue, Yui Uchida, Naoki Irie, Hiroyuki Takeda & Shinich Morishita

Centromeres and large-scale structural variants evolve and contribute to genome diversity during vertebrate speciation. Here Ichikawa et al perform de novo long-read genome assembly of three inbred medaka strains, and report long-range structure of centromeres and their methylation as well as correlation of structural variants with differential gene expression.

28 November 2017 | doi: 10.1038/s41467-017-01982-7
Genome  Genome informatics  Speciation  Transcriptomics 

Functional mapping and annotation of genetic associations with FUMA OPEN
Kyoko Watanabe, Erdogan Taskesen, Arjen van Bochoven & Danielle Posthuma

Prioritizing genetic variants is a major challenge in genome-wide association studies. Here, the authors develop FUMA, a web-based bioinformatics tool that uses a combination of positional, eQTL and chromatin interaction mapping to prioritize likely causal variants and genes.

28 November 2017 | doi: 10.1038/s41467-017-01261-5
Data integration  Genome-wide association studies 

Mantle hydration and the role of water in the generation of large igneous provinces OPEN
Jia Liu, Qun-Ke Xia, Takeshi Kuritani, Eero Hanski & Hao-Ran Yu

The genesis of large igneous provinces (LIPs) remains controversial. Here, the authors examine the water contents of picrites from the Emeishan LIP and find that despite high water contents, the elevated temperature and trace elements suggest a mantle plume from a hydrous deep reservoir rather than subduction zone related.

28 November 2017 | doi: 10.1038/s41467-017-01940-3
Geodynamics  Petrology 

Counter-intuitive influence of Himalayan river morphodynamics on Indus Civilisation urban settlements OPEN
Ajit Singh, Kristina J. Thomsen, Rajiv Sinha, Jan-Pieter Buylaert, Andrew Carter, Darren F. Mark, Philippa J. Mason, Alexander L. Densmore, Andrew S. Murray, Mayank Jain, Debajyoti Paul & Sanjeev Gupta

The Bronze-age Indus civilisation (4.6–3.9 ka) was thought to have been linked to the development of water resources in the Himalayas. Here, the authors show that along the former course of the Sutlej River the Indus settlements developed along the abandoned river valley rather than an active Himalayan river.

28 November 2017 | doi: 10.1038/s41467-017-01643-9
Archaeology  Geomorphology  Sedimentology 

Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma OPEN
Jose Mario Gonzalez-Meljem, Scott Haston, Gabriela Carreno, John R. Apps, Sara Pozzi, Christina Stache, Grace Kaushal, Alex Virasami, Leonidas Panousopoulos, Seyedeh Neda Mousavy-Gharavy, Ana Guerrero, Mamunur Rashid, Nital Jani, Colin R. Goding, Thomas S. Jacques, David J. Adams, Jesus Gil, Cynthia L. Andoniadou & Juan Pedro Martinez-Barbera

Senescent cells can promote tumour progression through the activation of a senescenceassociated secretory phenotype (SASP). Here, the authors show that SASP activation is associated with non-cell autonomous cell transformation and tumour initiation in an in vivo model of adamantinomatous craniopharyngioma.

28 November 2017 | doi: 10.1038/s41467-017-01992-5
Cancer stem cells  Paediatric cancer 

A Co3O4-CDots-C3N4 three component electrocatalyst design concept for efficient and tunable CO2 reduction to syngas OPEN
Sijie Guo, Siqi Zhao, Xiuqin Wu, Hao Li, Yunjie Zhou, Cheng Zhu, Nianjun Yang, Xin Jiang, Jin Gao, Liang Bai, Yang Liu, Yeshayahu Lifshitz, Shuit-Tong Lee & Zhenhui Kang

Simultaneous electrochemical reduction of CO2 and H+/H2O is an attractive renewable route to produce syngas mixtures. Here, the authors introduce a ternary Co3O4-CDots-C3N4 electrocatalyst that couples hydrogen evolution and CO2 reduction catalysts and achieves cheap, stable and tunable production of syngas.

28 November 2017 | doi: 10.1038/s41467-017-01893-7
Carbon capture and storage  Electrocatalysis  Environmental, health and safety issues  Renewable energy 

Induced cortical tension restores functional junctions in adhesion-defective carcinoma cells OPEN
Shoko Ito, Satoru Okuda, Masako Abe, Mari Fujimoto, Tetsuo Onuki, Tamako Nishimura & Masatoshi Takeichi

Cancer cells can disrupt cell-to-cell junctions, thus allowing migration and metastasis. Here starting from a chemical screening, Ito et al. reconstitute a step-by-step mechanism linking microtubule depolymerization and epithelial cell junction restoration.

28 November 2017 | doi: 10.1038/s41467-017-01945-y
Adherens junctions  Myosin 

Identification of a neural crest stem cell niche by Spatial Genomic Analysis OPEN
Antti Lignell, Laura Kerosuo, Sebastian J. Streichan, Long Cai & Marianne E. Bronner

Neural crest cells arise within the central nervous system, then migrate and contribute to a variety of cell types. Here, the authors use multiplex transcript analysis at single cell  resolution to define neural crest and neural subpopulations within the avian neural tube, including a neural crest stem cell niche.

28 November 2017 | doi: 10.1038/s41467-017-01561-w
Development of the nervous system  Fluorescence in situ hybridization  Stem-cell niche 

Quantum-disordered state of magnetic and electric dipoles in an organic Mott system OPEN
M. Shimozawa, K. Hashimoto, A. Ueda, Y. Suzuki, K. Sugii, S. Yamada, Y. Imai, R. Kobayashi, K. Itoh, S. Iguchi, M. Naka, S. Ishihara, H. Mori, T. Sasaki & M. Yamashita

The organic material κ-H3(Cat-EDT-TTF)2 has been suggested to exhibit a quantum spin liquid phase in which quantum fluctuations prevent the formation of magnetic order. Here, the authors show that this may be a result of fluctuations of hydrogen atoms, rather than more conventional geometric frustration.

28 November 2017 | doi: 10.1038/s41467-017-01849-x
Ferroelectrics and multiferroics  Magnetic properties and materials 

Methane- and dissolved organic carbon-fueled microbial loop supports a tropical subterranean estuary ecosystem OPEN
D. Brankovits, J. W. Pohlman, H. Niemann, M. B. Leigh, M. C. Leewis, K. W. Becker, T. M. Iliffe, F. Alvarez, M. F. Lehmann & B. Phillips

It remains unclear how oligotrophic habitats in subterranean estuaries sustain complex ecosystems. Here, using stable isotopic evidence from organic matter and pelagic shrimp, the authors show that a microbial loop fuelled by methane and dissolved organic carbon sustains the anchialine food web.

28 November 2017 | doi: 10.1038/s41467-017-01776-x
Carbon cycle  Ecosystem ecology  Marine chemistry 

Label-free nanoscale optical metrology on myelinated axons in vivo OPEN
Junhwan Kwon, Moonseok Kim, Hyejin Park, Bok-Man Kang, Yongjae Jo, Jae-Hwan Kim, Oliver James, Seok-Hyun Yun, Seong-Gi Kim, Minah Suh & Myunghwan Choi

Spectral reflectance has been used to achieve label-free, in vivo imaging of myelin, a membranous sheath that allows faster electrical conduction along neuronal axons. Here the authors extend this technique to measure nanoscale features, including changes following traumatic brain injury.

28 November 2017 | doi: 10.1038/s41467-017-01979-2
Imaging and sensing  Myelin biology and repair 

Simple spatial scaling rules behind complex cities OPEN
Ruiqi Li, Lei Dong, Jiang Zhang, Xinran Wang, Wen-Xu Wang, Zengru Di & H. Eugene Stanley

Cities can be treated as dynamic complex systems being controlled by the interactions among people, whilst the detail remains largely unknown. Li et al. use spatial attraction together with matching growth to unify population, roads, and socioeconomic interactions crossing ten representative cities.

28 November 2017 | doi: 10.1038/s41467-017-01882-w
Complex networks  Statistical physics 

The chromatin remodeling factor ISW-1 integrates organismal responses against nuclear and mitochondrial stress OPEN
Olli Matilainen, Maroun S. Bou Sleiman, Pedro M. Quiros, Susana M. D. A. Garcia & Johan Auwerx

Changes in chromatin structure have been linked to organismal ageing. Here the authors show that altered histone expression and mitochondrial stress during C. elegans development result in chromatin changes and a cytosolic stress response that affects organismal longevity, and depends on HSF-1 and the chromatin remodeller, ISW-1.

28 November 2017 | doi: 10.1038/s41467-017-01903-8
Ageing  Chaperones 

Oscillatory brain activity in spontaneous and induced sleep stages in flies OPEN
Melvyn H. W. Yap, Martyna J. Grabowska, Chelsie Rohrscheib, Rhiannon Jeans, Michael Troup, Angelique C. Paulk, Bart van Alphen, Paul J. Shaw & Bruno van Swinderen

Sleep in mammals comprises physiologically and functionally distinct stages. Here, the authors report a transitional sleep stage in Drosophila associated with 7–10 Hz oscillatory activity that can be obtained through activation of the sleep-promoting neurons of the dorsal fan-shaped body.

28 November 2017 | doi: 10.1038/s41467-017-02024-y
Extracellular recording  Sleep 

Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues OPEN
Ilya Y. Shadrin, Brian W. Allen, Ying Qian, Christopher P. Jackman, Aaron L. Carlson, Mark E. Juhas & Nenad Bursac

Cardiomyocytes derived from human induced pluripotent stem cells could be used to generate cardiac tissues for regenerative purposes. Here the authors describe a method to obtain large bioengineered heart tissues showing advanced maturation, functional features and engraftment capacity.

28 November 2017 | doi: 10.1038/s41467-017-01946-x
Cardiology  Induced pluripotent stem cells  Stem-cell differentiation  Tissue engineering 

Heterologous expression reveals the biosynthesis of the antibiotic pleuromutilin and generates bioactive semi-synthetic derivatives OPEN
Fabrizio Alberti, Khairunisa Khairudin, Edith Rodriguez Venegas, Jonathan A. Davies, Patrick M. Hayes, Christine L. Willis, Andy M. Bailey & Gary D. Foster

Pleuromutilin derivatives are potent antibacterial drugs obtained from Basidiomycete fungi. Here, the authors report the genetic characterisation of the steps involved in pleuromutilin biosynthesis through heterologous expression and generate a semi-synthetic pleuromutilin derivative with enhanced antibiotic activity.

28 November 2017 | doi: 10.1038/s41467-017-01659-1
Antibiotics  Chemical biology 

Hepatic protein tyrosine phosphatase receptor gamma links obesity-induced inflammation to insulin resistance OPEN
Xavier Brenachot, Giorgio Ramadori, Rafael M. Ioris, Christelle Veyrat-Durebex, Jordi Altirriba, Ebru Aras, Sanda Ljubicic, Daisuke Kohno, Salvatore Fabbiano, Sophie Clement, Nicolas Goossens, Mirko Trajkovski, Sheila Harroch, Francesco Negro & Roberto Coppari

During obesity, chronic inflammation leads to insulin resistance and diabetes. Here, Brenachot et al. show that Protein Tyrosine Phosphatase Receptor Gamma is upregulated in obesity by inflammatory signals and correlates with insulin resistance in humans. Its deletion in mouse models of obesity and inflammation ameliorates insulin resistance by suppressing glucose production.

28 November 2017 | doi: 10.1038/s41467-017-02074-2
Chronic inflammation  Type 2 diabetes 

Development of corticostriatal connectivity constrains goal-directed behavior during adolescence OPEN
Catherine Insel, Erik K. Kastman, Catherine R. Glenn & Leah H. Somerville

Adults adjust their cognitive performance according to the value of the outcome, but it is unclear whether adolescents do too. Here, authors show that adolescents do not adjust their cognitive effort according to value, and that this ability is mediated by connectivity between the striatum and prefrontal cortex.

28 November 2017 | doi: 10.1038/s41467-017-01369-8
Cognitive control  Motivation 

Bactofilin-mediated organization of the ParABS chromosome segregation system in Myxococcus xanthus  OPEN
Lin Lin, Manuel Osorio Valeriano, Andrea Harms, Lotte Søgaard-Andersen & Martin Thanbichler

The roles played by bactofilins, a widespread type of bacterial cytoskeletal elements, are unclear. Here, the authors show that the bactofilins BacNOP facilitate proper subcellular localization of the ParABS chromosome segregation system in the model organism Myxococcus xanthus.

28 November 2017 | doi: 10.1038/s41467-017-02015-z
Cellular microbiology  Chromosomes  Cytoskeleton 

Zero-field edge plasmons in a magnetic topological insulator OPEN
Alice C. Mahoney, James I. Colless, Lucas Peeters, Sebastian J. Pauka, Eli J. Fox, Xufeng Kou, Lei Pan, Kang L. Wang, David Goldhaber-Gordon & David J. Reilly

Direct measurement of edge transport in the quantum anomalous Hall effect can be made difficult due to the presence of parallel conductive paths. Here, Mahoney et al. report features associated with chiral edge plasmons, a signature of robust edge states, by probing the zero-field microwave response of a magnetised disk of Cr-(Bi,Sb)2Te3.

28 November 2017 | doi: 10.1038/s41467-017-01984-5
Quantum Hall  Topological insulators 

Genetic and pharmacological inhibition of microRNA-92a maintains podocyte cell cycle quiescence and limits crescentic glomerulonephritis OPEN
Carole Henique, Guillaume Bollée, Xavier Loyer, Florian Grahammer, Neeraj Dhaun, Marine Camus, Julien Vernerey, Léa Guyonnet, François Gaillard, Hélène Lazareth, Charlotte Meyer, Imane Bensaada, Luc Legrès, Takashi Satoh, Shizuo Akira, Patrick Bruneval, Stefanie Dimmeler, Alain Tedgui, Alexandre Karras, Eric Thervet et al.

Crescentic rapidly progressive glomerulonephritis is a severe form of glomerula disease characterized by podocyte proliferation and migration. Here Henique et al. demonstrate that inhibition of miRNA-92a prevents kidney failure by promoting the expression of CDK inhibitor p57Kip2 that regulates podocyte cell cycle.

28 November 2017 | doi: 10.1038/s41467-017-01885-7
Glomerular diseases  Mechanisms of disease  Molecular medicine 

Break-induced replication promotes formation of lethal joint molecules dissolved by Srs2 OPEN
Rajula Elango, Ziwei Sheng, Jessica Jackson, Jenna DeCata, Younis Ibrahim, Nhung T. Pham, Diana H. Liang, Cynthia J. Sakofsky, Alessandro Vindigni, Kirill S. Lobachev, Grzegorz Ira & Anna Malkova

Break-induced replication (BIR) is a double-strand break repair pathway that can lead to genomic instability. Here the authors show that the absence of Srs2 helicase during BIR leads to uncontrolled binding of Rad51 to single-stranded DNA, which promotes the formation of toxic intermediates that need to be resolved by Mus81 or Yen1.

27 November 2017 | doi: 10.1038/s41467-017-01987-2
DNA damage and repair  DNA replication  Genomic instability 

Mitochondrial dynamics controls anti-tumour innate immunity by regulating CHIP-IRF1 axis stability OPEN
Zhengjun Gao, Yiyuan Li, Fei Wang, Tao Huang, Keqi Fan, Yu Zhang, Jiangyan Zhong, Qian Cao, Tong Chao, Junling Jia, Shuo Yang, Long Zhang, Yichuan Xiao, Ji-Yong Zhou, Xin-Hua Feng & Jin Jin

Macrophage metabolism controls differentiation and subsequent adaptive immune responses. Here the authors show that mitochondrial membrane protein Fam73b regulates TLR-mediated mitochondrial switching of fusion to fission to induce IL-12 production via accumulation of Parkin and stabilization of IRF1 in macrophages, resulting in control of anti-tumor immunity in mice.

27 November 2017 | doi: 10.1038/s41467-017-01919-0
Acute inflammation  Innate immunity  Mitochondria  Tumour immunology 

A very large-scale microelectrode array for cellular-resolution electrophysiology OPEN
David Tsai, Daniel Sawyer, Adrian Bradd, Rafael Yuste & Kenneth L. Shepard

Large electronics limit low-noise, non-invasive electrophysiological measurements to a thousand simultaneously recording channels. Here the authors build an array of 65k simultaneously recording and stimulating electrodes and use it to sort and classify single neurons across the entire mouse retina.

27 November 2017 | doi: 10.1038/s41467-017-02009-x
Electrophysiology  Retina  Techniques and instrumentation 

Critical role of the HDAC6–cortactin axis in human megakaryocyte maturation leading to a proplatelet-formation defect OPEN
Kahia Messaoudi, Ashfaq Ali, Rameez Ishaq, Alberta Palazzo, Dominika Sliwa, Olivier Bluteau, Sylvie Souquère, Delphine Muller, Khadija M. Diop, Philippe Rameau, Valérie Lapierre, Jean-Pierre Marolleau, Patrick Matthias, Isabelle Godin, Gérard Pierron, Steven G. Thomas, Stephen P. Watson, Nathalie Droin, William Vainchenker, Isabelle Plo et al.

Histone deacetylase (HDAC) inhibitors, a class of cancer therapeutics, cause thrombocytopenia via an unknown mechanism. Here, the authors show that HDAC6 inhibition impairs proplatelet formation in human megakaryocytes, and show that this is linked to hyperacetylation of the actin-binding protein cortactin.

27 November 2017 | doi: 10.1038/s41467-017-01690-2
Acetylation  Cytoskeleton  Platelets 

Cellular microRNA networks regulate host dependency of hepatitis C virus infection OPEN
Qisheng Li, Brianna Lowey, Catherine Sodroski, Siddharth Krishnamurthy, Hawwa Alao, Helen Cha, Stephan Chiu, Ramy El-Diwany, Marc G. Ghany & T. Jake Liang

Using genome-wide miRNA mimic and hairpin inhibitor screens, Li et al. identify 31 miRNAs that either inhibit or promote hepatitis C virus (HCV) replication at different steps of the viral life cycle. Furthermore, human liver biopsies show that HCV down-regulates identified miRNAs with antiviral function.

27 November 2017 | doi: 10.1038/s41467-017-01954-x
Hepatitis C virus  High-throughput screening  miRNAs  Virus–host interactions 

Novel peptide probes to assess the tensional state of fibronectin fibers in cancer OPEN
Simon Arnoldini, Alessandra Moscaroli, Mamta Chabria, Manuel Hilbert, Samuel Hertig, Roger Schibli, Martin Béhé & Viola Vogel

The extracellular matrix is under variable strain, but we lack the tools to detect differences in strain. Here the authors develop a probe based on a bacterial fibronectin-binding peptide that binds to relaxed fibronectin fibrils and detects relaxed matrix in cell culture, tissue slices and in vivo.

27 November 2017 | doi: 10.1038/s41467-017-01846-0
Cancer screening  Diagnostic markers  Sensors and probes  Tumour heterogeneity 

Gate-tunable large magnetoresistance in an all-semiconductor spin valve device OPEN
M. Oltscher, F. Eberle, T. Kuczmik, A. Bayer, D. Schuh, D. Bougeard, M. Ciorga & D. Weiss

The development of spin field effect transistors has been hampered by the low magnetoresistance in the semiconductor spin valve. Here the authors report large and tunable magnetoresistance in a lateral 2DES-based spin valve geometry due to finite electric field effects at the ferromagnet-semiconductor interface.

27 November 2017 | doi: 10.1038/s41467-017-01933-2
Electronic devices  Spintronics 

Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes OPEN
Demian Burguera, Yamile Marquez, Claudia Racioppi, Jon Permanyer, Antonio Torres-Méndez, Rosaria Esposito, Beatriz Albuixech-Crespo, Lucía Fanlo, Ylenia D’Agostino, Andre Gohr, Enrique Navas-Perez, Ana Riesgo, Claudia Cuomo, Giovanna Benvenuto, Lionel A. Christiaen, Elisa Martí, Salvatore D’Aniello, Antonietta Spagnuolo, Filomena Ristoratore, Maria Ina Arnone et al.

Epithelial-mesenchymal interplays are essential to many ontogenetic processes in vertebrates. Here Burguera et al. show diverse embryonic morphogenetic processes regulated by Epithelial Splicing Regulatory Protein (Esrp) in different deuterostome species.

27 November 2017 | doi: 10.1038/s41467-017-01961-y
Evolutionary developmental biology  Transcriptomics 

Dual impact of elevated temperature on plant defence and bacterial virulence in Arabidopsis  OPEN
Bethany Huot, Christian Danve M. Castroverde, André C. Velásquez, Emily Hubbard, Jane A. Pulman, Jian Yao, Kevin L. Childs, Kenichi Tsuda, Beronda L. Montgomery & Sheng Yang He

Temperature is known to influence plant disease development. Here Huot et al. show that elevated temperature can enhance Pseudomonas syringae effector delivery into plant cells and suppress SA biosynthesis while also finding a temperature-sensitive branch of the SA signaling pathway in Arabidopsis.

27 November 2017 | doi: 10.1038/s41467-017-01674-2
Biotic  Virulence 

Structural basis for TNA synthesis by an engineered TNA polymerase OPEN
Nicholas Chim, Changhua Shi, Sujay P. Sau, Ali Nikoomanzar & John C. Chaput

The laboratory-evolved polymerase Kod-RI catalyzes α-L-threose nucleic acid (TNA) synthesis. Here, the authors present Kod-RI crystal structures that give insights into how TNA triphosphates are selected and extended in a template-dependent manner, which will help to engineer improved TNA polymerases for synthetic genetics applications.

27 November 2017 | doi: 10.1038/s41467-017-02014-0
DNA-binding proteins  Nucleic acids  X-ray crystallography 

Vps34 PI 3-kinase inactivation enhances insulin sensitivity through reprogramming of mitochondrial metabolism OPEN
Benoit Bilanges, Samira Alliouachene, Wayne Pearce, Daniele Morelli, Gyorgy Szabadkai, Yuen-Li Chung, Gaëtan Chicanne, Colin Valet, Julia M. Hill, Peter J. Voshol, Lucy Collinson, Christopher Peddie, Khaled Ali, Essam Ghazaly, Vinothini Rajeeve, Georgios Trichas, Shankar Srinivas, Claire Chaussade, Rachel S. Salamon, Jonathan M. Backer et al.

Vps34 is a lipid kinase conserved from yeast to humans and involved in in intracellular vesicular trafficking and autophagy. Here Bilanges et al. show that inhibition of this kinase in mice improves glucose tolerance and diet-induced steatosis by modulating mitochondrial respiration and metabolism.

27 November 2017 | doi: 10.1038/s41467-017-01969-4
Energy metabolism  Type 2 diabetes 

The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery OPEN
Ramesh Kumar, Román González-Prieto, Zhenyu Xiao, Matty Verlaan-de Vries & Alfred C. O. Vertegaal

SUMO and ubiquitin are key signal transducers in several cellular processes including the DNA-damage response. Here the authors describe a method for selective enrichment of ubiquitin substrates for E3 ligases from complex cellular proteomes and identify the SUMO conjugation machinery as direct RNF4 substrates.

27 November 2017 | doi: 10.1038/s41467-017-01900-x
DNA damage and repair  Proteomic analysis 

The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1 OPEN
Adam J. Middleton, Rhesa Budhidarmo, Anubrita Das, Jingyi Zhu, Martina Foglizzo, Peter D. Mace & Catherine L. Day

TRAF6 is a RING E3 ligase that builds Lys63-linked ubiquitin chains. Here, the authors present the crystal structure of TRAF6 bound to the Ubc13~Ub conjugate, which, together with biochemical assays, reveals the role of the zinc finger domains and why RING dimerisation is required for TRAF6 activity.

27 November 2017 | doi: 10.1038/s41467-017-01665-3
Cell signalling  Enzyme mechanisms  X-ray crystallography 

Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies from psychotic patients OPEN

Autoantibodies are found in neuropsychiatric conditions but without clear cellular mechanism and disease relevance. This study shows higher prevalence of autoantibodies against NMDAR receptors in schizophrenia patients, and patient-associated antibody can alter synaptic receptor trafficking and plasticity.

27 November 2017 | doi: 10.1038/s41467-017-01700-3
Cellular neuroscience  Psychosis  Synaptic transmission 

A transcribed enhancer dictates mesendoderm specification in pluripotency OPEN

Long noncoding RNAs (lncRNAs) are key regulators of lineage specification during development. Here, the authors investigate remodeling of enhancers and regulation of the lncRNA transcriptome during mesendoderm specification, and identify a pluripotent stage-specific transcribed enhancer controlling adoption of the mesendodermal cell fate.

27 November 2017 | doi: 10.1038/s41467-017-01804-w
Differentiation  Embryonic stem cells 

A protein interaction mechanism for suppressing the mechanosensitive Piezo channels OPEN
Tingxin Zhang, Shaopeng Chi, Fan Jiang, Qiancheng Zhao & Bailong Xiao

Mechanosensitive Piezo channels are important for a wide range of mechanotransduction processes. Here the authors show that Piezos interact with sarcoplasmic /endoplasmic-reticulum Ca2+ ATPases (SERCA) and give mechanistic insights into mechanogating and SERCA2-mediated regulation of Piezo1.

27 November 2017 | doi: 10.1038/s41467-017-01712-z
Ion channel signalling  Permeation and transport 

Rods progressively escape saturation to drive visual responses in daylight conditions OPEN
Alexandra Tikidji-Hamburyan, Katja Reinhard, Riccardo Storchi, Johannes Dietter, Hartwig Seitter, Katherine E. Davis, Saad Idrees, Marion Mutter, Lauren Walmsley, Robert A. Bedford, Marius Ueffing, Petri Ala-Laurila, Timothy M. Brown, Robert J. Lucas & Thomas A. Münch

Rod photoreceptors are thought to be saturated under bright light. Here, the authors describe the physiological parameters that mediate response saturation of rod photoreceptors in mouse retina, and show that rods can drive visual responses in photopic conditions.

27 November 2017 | doi: 10.1038/s41467-017-01816-6
Network models  Neurodegenerative diseases  Neurophysiology  Retina 

A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer-based chemical sensor OPEN
M. J. Bryant, J. M. Skelton, L. E. Hatcher, C. Stubbs, E. Madrid, A. R. Pallipurath, L. H. Thomas, C. H. Woodall, J. Christensen, S. Fuertes, T. P. Robinson, C. M. Beavers, S. J. Teat, M. R. Warren, F. Pradaux-Caggiano, A. Walsh, F. Marken, D. R. Carbery, S. C. Parker, N. B. McKeown et al.

Solid state Pt(II)-pincer complexes exhibiting vapochromic responses show promise for chemical sensing applications, but their slow responses typically limit their utility. Here, Raithby and colleagues design a Pt(II)-pincer complex with a subsecond, highly-selective vapochromic response to water and methanol.

27 November 2017 | doi: 10.1038/s41467-017-01941-2
Coordination chemistry  Electronic materials  Inorganic chemistry  Sensors 

Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment OPEN
Yanyun Gu, Xiaokai Wang, Junhua Li, Yifei Zhang, Huanzi Zhong, Ruixin Liu, Dongya Zhang, Qiang Feng, Xiaoyan Xie, Jie Hong, Huahui Ren, Wei Liu, Jing Ma, Qing Su, Hongmei Zhang, Jialin Yang, Xiaoling Wang, Xinjie Zhao, Weiqiong Gu, Yufang Bi et al.

The authors examine the effects of antidiabetic medication on the gut microbiome and bile acid composition and show that these data can be used to stratify treatment regimens for type 2 diabetes.

27 November 2017 | doi: 10.1038/s41467-017-01682-2
Diabetes  Metagenomics  Microbiome  Translational research 

Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression OPEN
Jianqin Lu, Xiangsheng Liu, Yu-Pei Liao, Felix Salazar, Bingbing Sun, Wen Jiang, Chong Hyun Chang, Jinhong Jiang, Xiang Wang, Anna M. Wu, Huan Meng & Andre E. Nel

Pancreatic cancer remains difficult to treat mainly due to the drug delivery challenges posed by a strong stromal component. Here the authors develop nanocarriers that improve drug delivery efficiency and engage the host immune system against the tumor resulting in reduction of tumor growth and metastasis.

27 November 2017 | doi: 10.1038/s41467-017-01651-9
Cancer immunotherapy  Cell death and immune response  Drug delivery  Nanoparticles 

Insight into partial agonism by observing multiple equilibria for ligand-bound and Gs-mimetic nanobody-bound β1-adrenergic receptor OPEN
Andras S. Solt, Mark J. Bostock, Binesh Shrestha, Prashant Kumar, Tony Warne, Christopher G. Tate & Daniel Nietlispach

β1-adrenergic receptors are expressed in cardiac tissue and stimulated by the sympathetic nervous system. Here, the authors use NMR spectroscopy to unravel the conformational diversity upon β1-adrenergic receptor activation and provide structural insights into partial agonism and basal activity.

27 November 2017 | doi: 10.1038/s41467-017-02008-y
G protein-coupled receptors  Solution-state NMR 

Ingestion of artificial sweeteners leads to caloric frustration memory in Drosophila  OPEN
Pierre-Yves Musso, Aurélie Lampin-Saint-Amaux, Paul Tchenio & Thomas Preat

While non-caloric artificial sweeteners (NAS) are used as food additives, it’s unclear whether animals perceive NAS as positive or negative percept. Here, Musso and colleagues show in Drosophila that NAS is a negative percept, encoded in a new type of memory.

27 November 2017 | doi: 10.1038/s41467-017-01989-0
Long-term memory  Reward 

Singlet oxygen-mediated selective C–H bond hydroperoxidation of ethereal hydrocarbons OPEN
Arunachalam Sagadevan, Kuo Chu Hwang & Ming-Der Su

Singlet oxygen is known to react with carbon–carbon double bonds. Here, the authors show the unusual functionalization of α-ethereal C–H bonds mediated by singlet oxygen under mild conditions to afford lactones and hydroperoxide products.

27 November 2017 | doi: 10.1038/s41467-017-01906-5
Chemical safety  Excited states  Reaction mechanisms 

T cell receptor β-chains display abnormal shortening and repertoire sharing in type 1 diabetes OPEN
Iria Gomez-Tourino, Yogesh Kamra, Roman Baptista, Anna Lorenc & Mark Peakman

T cell receptors are generated by somatic gene recombination, and are normally selected against autoreactivity. Here the authors show that CD4 T cells from patients with autoimmune type 1 diabetes have shorter TCRβ sequences, broader repertoire diversity, and more repertoire sharing than those from healthy individuals.

27 November 2017 | doi: 10.1038/s41467-017-01925-2
Autoimmunity  Immunogenetics  Lymphocytes  VDJ recombination 

A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia OPEN
Hailey J. Knox, Jamila Hedhli, Tae Wook Kim, Kian Khalili, Lawrence W. Dobrucki & Jefferson Chan

Hypoxia is a hallmark of many diseases including cancer and ischemia, and detection can be invasive and of low resolution and specificity. Here the authors show a hypoxia probe that converts non-ionizing light to ultrasound, which enables the acquisition of high-resolution 3D images in deep tissue.

27 November 2017 | doi: 10.1038/s41467-017-01951-0
Chemical tools  Fluorescent probes  Imaging studies 

Changes in cortical network connectivity with long-term brain-machine interface exposure after chronic amputation OPEN
Karthikeyan Balasubramanian, Mukta Vaidya, Joshua Southerland, Islam Badreldin, Ahmed Eleryan, Kazutaka Takahashi, Kai Qian, Marc W. Slutzky, Andrew H. Fagg, Karim Oweiss & Nicholas G. Hatsopoulos

Previous studies have shown short-term plasticity in single neurons or local field potentials during brain-machine interface (BMI) training. Here the authors report long-term changes in functional connectivity of motor cortex neuronal ensemble activity as chronically amputated monkeys learn to operate a BMI.

27 November 2017 | doi: 10.1038/s41467-017-01909-2
Brain–machine interface  Neural circuits  Neural decoding  Operant learning 

Reconstitution of the complete pathway of ITS2 processing at the pre-ribosome OPEN
Lisa Fromm, Sebastian Falk, Dirk Flemming, Jan Michael Schuller, Matthias Thoms, Elena Conti & Ed Hurt

Excision of internal transcribed spacer 2 (ITS2) within eukaryotic pre-ribosomal RNA is essential for ribosome function. Here, the authors reconstitute the entire cycle of ITS2 processing in vitro using purified components, providing insights into the cleavage process and demonstrating that 26S pre-rRNA processing necessarily precedes 7S pre-rRNA processing.

27 November 2017 | doi: 10.1038/s41467-017-01786-9
Ribosomal proteins  Ribosome  RNA  RNA decay 

Mapping microscale wetting variations on biological and synthetic water-repellent surfaces OPEN
Ville Liimatainen, Maja Vuckovac, Ville Jokinen, Veikko Sariola, Matti J. Hokkanen, Quan Zhou & Robin H. A. Ras

Real-world surfaces exhibit spatially varying wettability, which affects water repellency and droplet behaviour on such surfaces. Here, the authors use scanning droplet adhesion microscopy to create wetting maps that visualize variations in wettability with a spatial resolution down to 10 μm.

27 November 2017 | doi: 10.1038/s41467-017-01510-7
Bioinspired materials  Characterization and analytical techniques  Imaging  Scanning probe microscopy 

Transcribed ultraconserved region 339 promotes carcinogenesis by modulating tumor suppressor microRNAs OPEN
Ivan Vannini, Petra M. Wise, Kishore B. Challagundla, Meropi Plousiou, Mirco Raffini, Erika Bandini, Francesca Fanini, Giorgia Paliaga, Melissa Crawford, Manuela Ferracin, Cristina Ivan, Linda Fabris, Ramana V. Davuluri, Zhiyi Guo, Maria Angelica Cortez, Xinna Zhang, Lu Chen, Shuxing Zhang, Cecilia Fernandez-Cymering, Leng Han et al.

T-UCRs encode long non-coding RNAs implicated in human carcinogenesis, but the underlying mechanisms are poorly understood. Here, the authors identify uc.339 as an oncogene in lung cancer that is upregulated through the loss of TP53 and promotes Cyclin E activation by entrapping regulatory miRNAs.

27 November 2017 | doi: 10.1038/s41467-017-01562-9
Long non-coding RNAs  Mechanisms of disease  Non-small-cell lung cancer 

Strain-resolved analysis of hospital rooms and infants reveals overlap between the human and room microbiome OPEN
Brandon Brooks, Matthew R. Olm, Brian A. Firek, Robyn Baker, Brian C. Thomas, Michael J. Morowitz & Jillian F. Banfield

It is thought that the hospital environment may contribute to infant microbiome development. Here, Brooks et al. present a genome-resolved metagenomic study of microbial genotypes from the infant gut and from neonatal intensive care unit rooms, showing that some strains are found in both infants and rooms.

27 November 2017 | doi: 10.1038/s41467-017-02018-w
Metagenomics  Microbiome 

STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells OPEN
Paula Nunes-Hasler, Sophia Maschalidi, Carla Lippens, Cyril Castelbou, Samuel Bouvet, Daniele Guido, Flavien Bermont, Esen Y. Bassoy, Nicolas Page, Doron Merkler, Stéphanie Hugues, Denis Martinvalet, Bénédicte Manoury & Nicolas Demaurex

STIM proteins sense Ca2+ depletion in the ER and activate store-operated Ca2+-entry (SOCE) in response, a process associated with dendritic cell functions. Here the authors show STIM1 is the major isoform controlling SOCE in mouse dendritic cells and provide a mechanism for its requirement in antigen cross-presentation.

24 November 2017 | doi: 10.1038/s41467-017-01600-6
Antigen-presenting cells  Calcium signalling 

DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells OPEN
Hiro Sato, Atsuko Niimi, Takaaki Yasuhara, Tiara Bunga Mayang Permata, Yoshihiko Hagiwara, Mayu Isono, Endang Nuryadi, Ryota Sekine, Takahiro Oike, Sangeeta Kakoti, Yuya Yoshimoto, Kathryn D. Held, Yoshiyuki Suzuki, Koji Kono, Kiyoshi Miyagawa, Takashi Nakano & Atsushi Shibata

PD-L1 is upregulated in many cancers due to exogenous cellular stress. Here the authors show that PD-L1 is upregulated in response to DNA double strand breaks via STAT and IRF1 signalling.

24 November 2017 | doi: 10.1038/s41467-017-01883-9
Cancer therapy  Cell signalling 

Origami silicon optoelectronics for hemispherical electronic eye systems OPEN
Kan Zhang, Yei Hwan Jung, Solomon Mikael, Jung-Hun Seo, Munho Kim, Hongyi Mi, Han Zhou, Zhenyang Xia, Weidong Zhou, Shaoqin Gong & Zhenqiang Ma

Hemispherical format has been adopted in camera systems to better mimic human eyes, yet the current designs rely on complicated fabrications. Here, Zhang et al. show an origami-inspired approach that enables planar silicon-based photodetector arrays to reshape into concave or convex geometries.

24 November 2017 | doi: 10.1038/s41467-017-01926-1
Electrical and electronic engineering  Electronic devices  Materials for optics  Optoelectronic devices and components 

Feature-based learning improves adaptability without compromising precision OPEN
Shiva Farashahi, Katherine Rowe, Zohra Aslami, Daeyeol Lee & Alireza Soltani

Learning about a rewarded outcome is complicated by the fact that a choice often incorporates multiple features with differing association with the reward. Here the authors demonstrate that feature-based learning is an efficient and adaptive strategy in dynamically changing environments.

24 November 2017 | doi: 10.1038/s41467-017-01874-w
Decision  Learning algorithms 

Microbial volatile communication in human organotypic lung models OPEN
Layla J. Barkal, Clare L. Procknow, Yasmín R. Álvarez-García, Mengyao Niu, José A. Jiménez-Torres, Rebecca A. Brockman-Schneider, James E. Gern, Loren C. Denlinger, Ashleigh B. Theberge, Nancy P. Keller, Erwin Berthier & David J. Beebe

There is a need for improved in vitro models of host-microbe interactions in the lung. Here, Barkal et al. present a microscale organotypic model of the human bronchiole for studying pulmonary infection, including volatile compound communication between microbial populations and host cells.

24 November 2017 | doi: 10.1038/s41467-017-01985-4
Antimicrobial responses  Chemokines  Microbial communities  Tissue engineering 

Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma OPEN
Raffaele Simeoli, Karli Montague, Hefin R. Jones, Laura Castaldi, David Chambers, Jayne H. Kelleher, Valentina Vacca, Thomas Pitcher, John Grist, Hadil Al-Ahdal, Liang-Fong Wong, Mauro Perretti, Johnathan Lai, Peter Mouritzen, Paul Heppenstall & Marzia Malcangio

Exosomes are known to contain microRNAs (miRs). Here the authors show that dorsal root ganglion neurons release exosomes containing miR-21-5p, which contributes to inflammatory cell recruitment following peripheral nerve injury.

24 November 2017 | doi: 10.1038/s41467-017-01841-5
Chronic pain  miRNAs 

Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility OPEN
Sumana R. Chintalapudi, Doaa Maria, Xiang Di Wang, Jessica N. Cooke Bailey, Pirro G. Hysi, Janey L. Wiggs, Robert W. Williams & Monica M. Jablonski

Elevated intraocular pressure (IOP) is a heritable risk factor for primary open angle glaucoma. Using forward mouse genetics, cell biology, pharmacology and human genetic data, the authors identify CACNA2D1 as an IOP risk gene that can be therapeutically targeted by the drug pregabalin in animal models.

24 November 2017 | doi: 10.1038/s41467-017-00837-5
Eye diseases  Gene regulation  Genetics 

Oncogenic PIK3CA induces centrosome amplification and tolerance to genome doubling OPEN
Inma M. Berenjeno, Roberto Piñeiro, Sandra D. Castillo, Wayne Pearce, Nicholas McGranahan, Sally M. Dewhurst, Valerie Meniel, Nicolai J. Birkbak, Evelyn Lau, Laurent Sansregret, Daniele Morelli, Nnennaya Kanu, Shankar Srinivas, Mariona Graupera, Victoria E. R. Parker, Karen G. Montgomery, Larissa S. Moniz, Cheryl L. Scudamore, Wayne A. Phillips, Robert K. Semple et al.

Activated PI3K causes cancer, but the role of active PI3K mutations in early stages of malignancy are unclear. Here, the authors show in a mouse model that active PI3K induces centrosome amplification via AKT, ROCK, CDK2/Cyclin E and nucleophosmin, and increased tolerance of genome doubling.

24 November 2017 | doi: 10.1038/s41467-017-02002-4
Cancer  Growth factor signalling  Oncogenes 

Reconciling grain growth and shear-coupled grain boundary migration OPEN
Spencer L. Thomas, Kongtao Chen, Jian Han, Prashant K. Purohit & David J. Srolovitz

Conventional grain growth models assume the velocity of a grain boundary is proportional to its curvature but cannot account for the many deviations observed experimentally. Here, the authors present a model that connects grain growth directly to the disconnection mechanism of grain boundary migration and can account for these deviations.

24 November 2017 | doi: 10.1038/s41467-017-01889-3
Atomistic models  Coarse-grained models  Structural properties 

Regulatory T cells control toxicity in a humanized model of IL-2 therapy OPEN
Yan Li, Helene Strick-Marchand, Ai Ing Lim, Jiazi Ren, Guillemette Masse-Ranson, Dan Li, Gregory Jouvion, Lars Rogge, Sophie Lucas, Bin Li & James P. Di Santo

High dose IL-2 is a viable treatment option for cancer immune therapy, but the underlying mechanism for the accompanying undesirable morbidity is unclear. Here the authors show, using human immune system mouse models, that regulatory T cells and their functions on effector T cells are essential modulators of the related pathogenesis.

24 November 2017 | doi: 10.1038/s41467-017-01570-9
Immunosuppression  Interleukins  Regulatory T cells  Translational immunology 

Spectroscopic detection of halogen bonding resolves dye regeneration in the dye-sensitized solar cell OPEN
Fraser G. L. Parlane, Chantal Mustoe, Cameron W. Kellett, Sarah J. Simon, Wesley B. Swords, Gerald J. Meyer, Pierre Kennepohl & Curtis P. Berlinguette

Dye-sensitized solar cells rely on molecular dyes to absorb light and conduct electrons. Parlane et al. show that weak forces such as hydrogen bonding can be responsible for the dye regeneration step of solar cells and have an impact on the photovoltage and the efficiency.

24 November 2017 | doi: 10.1038/s41467-017-01726-7
Energy  Solar cells 

Antagonistic bacteria disrupt calcium homeostasis and immobilize algal cells OPEN
Prasad Aiyar, Daniel Schaeme, María García-Altares, David Carrasco Flores, Hannes Dathe, Christian Hertweck, Severin Sasso & Maria Mittag

Predatory or competitive interactions between microbes are poorly understood but likely influence global nutrient cycles. Here, the authors show that Pseudomonas bacteria could immobilize algal cells, potential prey, by releasing secondary metabolites that induce a Ca2+ signal and algal deflagellation.

24 November 2017 | doi: 10.1038/s41467-017-01547-8
Bacteria  Microbial ecology  Natural products  Plant signalling 

Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy OPEN
Wei Chen, Rui Tian, Can Xu, Bryant C. Yung, Guohao Wang, Yijing Liu, Qianqian Ni, Fuwu Zhang, Zijian Zhou, Jingjing Wang, Gang Niu, Ying Ma, Liwu Fu & Xiaoyuan Chen

Diabetes treatments often rely on frequent and scheduled drug administration, which reduces patient compliance and increases treatment cost. Here, the authors develop a microneedle-array patch that separately loads drug-releasing module and glucose-sensing element for on-demand, long-term diabetes therapy.

24 November 2017 | doi: 10.1038/s41467-017-01764-1
Drug delivery  Molecular medicine 

A galactic microquasar mimicking winged radio galaxies OPEN
Josep Martí, Pedro L. Luque-Escamilla, Valentí Bosch-Ramon & Josep M. Paredes

Winged radio galaxies possess wing features detectable at radio wavelengths, yet the physical interpretation of such extragalactic radio sources remains elusive. Here, the authors report the observation of a downsized Z-shaped radio emission from the Galactic microquasar GRS 1758-258, shedding light on the formation of wings in radio galaxies given its strongly  reminiscent winged morphology.

24 November 2017 | doi: 10.1038/s41467-017-01976-5
Galaxies and clusters  High-energy astrophysics 

NSD1- and NSD2-damaging mutations define a subset of laryngeal tumors with favorable prognosis OPEN
Suraj Peri, Evgeny Izumchenko, Adrian D. Schubert, Michael J. Slifker, Karen Ruth, Ilya G. Serebriiskii, Theresa Guo, Barbara A. Burtness, Ranee Mehra, Eric A. Ross, David Sidransky & Erica A. Golemis

The authors use an integrative clustering approach to identify two laryngeal cancer clusters with distinct prognosis and show that mutations damaging the NSD1 and NSD2 methyltransferases segregate to the cluster with favorable prognosis, and independently predict longer survival in patients with laryngeal, but not other head and neck cancers.

24 November 2017 | doi: 10.1038/s41467-017-01877-7
Data mining  Head and neck cancer  Prognostic markers 

Simultaneous fabrication of line and dot dual nanopatterns using miktoarm block copolymer with photocleavable linker OPEN
Chungryong Choi, Jichoel Park, Kanniyambatti L. Vincent Joseph, Jaeyong Lee, Seonghyeon Ahn, Jongheon Kwak, Kyu Seong Lee & Jin Kon Kim

Block copolymers that form nanodomains and are used in nanolithography usually do not form nanopatterns with multiple shapes. Here the authors report a block copolymer that allows for UV- induced cleavage of one arm and demonstrate the transformation of the cylindrical to the lamellar nanodomain.

24 November 2017 | doi: 10.1038/s41467-017-02019-9
Molecular self-assembly  Polymer synthesis  Self-assembly 

Transformation of the head-direction signal into a spatial code OPEN
Adrien Peyrache, Natalie Schieferstein & Gyorgy Buzsáki

A cognitive map of space must integrate allocentric cues such as head direction (HD) with various egocentric cues. Here the authors report that anterior thalamic (ADn) neurons encode a pure HD signal, while neurons in post-subiculum represent a conjunction of HD and egocentric cues such as body posture with respect to environment boundaries.

24 November 2017 | doi: 10.1038/s41467-017-01908-3
Neural circuits  Sensory processing 

Programmed biomolecule delivery to enable and direct cell migration for connective tissue repair OPEN
Feini Qu, Julianne L. Holloway, John L. Esterhai, Jason A. Burdick & Robert L. Mauck

Dense connective tissues do not easily heal, in part due to a low supply of reparative cells. Here, the authors develop a fibrous scaffold for meniscal repair that sequentially releases collagenase and a growth factor at the injury site, breaking down the extracellular matrix and recruiting endogenous cells.

24 November 2017 | doi: 10.1038/s41467-017-01955-w
Biomedical engineering  Biomedical materials  Drug delivery  Tissue engineering 

Quenching protein dynamics interferes with HIV capsid maturation OPEN
Mingzhang Wang, Caitlin M. Quinn, Juan R. Perilla, Huilan Zhang, Randall Shirra Jr., Guangjin Hou, In-Ja Byeon, Christopher L. Suiter, Sherimay Ablan, Emiko Urano, Theodore J. Nitz, Christopher Aiken, Eric O. Freed, Peijun Zhang, Klaus Schulten, Angela M. Gronenborn & Tatyana Polenova

The process of HIV particle maturation involves complex molecular transitions. Here the authors combine NMR spectroscopy, cryo-EM, and molecular dynamics simulations to provide insight into the conformational equilibria in CA-SP1 assemblies relevant to HIV-1 maturation intermediates formation.

24 November 2017 | doi: 10.1038/s41467-017-01856-y
Computational biophysics  Solid-state NMR  Virology 

Multicomponent mapping of boron chemotypes furnishes selective enzyme inhibitors OPEN
Joanne Tan, Armand B. Cognetta III, Diego B. Diaz, Kenneth M. Lum, Shinya Adachi, Soumajit Kundu, Benjamin F. Cravatt & Andrei K. Yudin

Heteroatom-rich organoboron compounds are promising modulators of enzyme activity. Here, the authors report a library of aminocyanoboronates as serine hydrolases inhibitors with the most potent compound showing in vivo and in vitro nanomolar activity and high selectivity towards human ABHD3 hydrolase.

24 November 2017 | doi: 10.1038/s41467-017-01319-4
Chemical libraries  Synthetic chemistry methodology  Small molecules 

Caldera resurgence driven by magma viscosity contrasts OPEN
Federico Galetto, Valerio Acocella & Luca Caricchi

Following a large caldera creating volcanic eruption, caldera resurgence may occur as magma accumulation takes place, but this rarely leads to another a major eruption. Here, the authors using thermal and experimental models show that caldera resurgence is driven by magma viscosity contrasts.

24 November 2017 | doi: 10.1038/s41467-017-01632-y
Petrology  Volcanology 

Anaerobic microsites have an unaccounted role in soil carbon stabilization OPEN
Marco Keiluweit, Tom Wanzek, Markus Kleber, Peter Nico & Scott Fendorf

Mechanisms controlling soil carbon storage and feedbacks to the climate system remain poorly constrained. Here, the authors show that anaerobic microsites stabilize soil carbon by shifting microbial metabolism to less efficient anaerobic respiration and protecting reduced organic compounds from decomposition.

24 November 2017 | doi: 10.1038/s41467-017-01406-6
Carbon cycle 

Single-cell absolute contact probability detection reveals chromosomes are organized by multiple low-frequency yet specific interactions OPEN
Diego I. Cattoni, Andrés M. Cardozo Gizzi, Mariya Georgieva, Marco Di Stefano, Alessandro Valeri, Delphine Chamousset, Christophe Houbron, Stephanie Déjardin, Jean-Bernard Fiche, Inma González, Jia-Ming Chang, Thomas Sexton, Marc A. Marti-Renom, Frédéric Bantignies, Giacomo Cavalli & Marcelo Nollmann

Eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that exist at the kilo-megabase scale. Here Cattoni et al. combine super-resolution microscopy with DNA-labeling methods to quantify absolute frequencies of interactions within TADs.

24 November 2017 | doi: 10.1038/s41467-017-01962-x
Computational biology and bioinformatics  Epigenomics  Nanoscale biophysics  Super-resolution microscopy 

An activity-dependent proximity ligation platform for spatially resolved quantification of active enzymes in single cells OPEN
Gang Li, Jeffrey E. Montgomery, Mark A. Eckert, Jae Won Chang, Samantha M. Tienda, Ernst Lengyel & Raymond E. Moellering

The interrogation of enzyme activity involves the ensemble averaging of many cells, loss of spatial relationships and is often biased to abundant proteins. Here the authors develop activity-dependent proximity ligation to quantify enzyme activity at the cellular and sub-cellular level in relevant biological contexts.

24 November 2017 | doi: 10.1038/s41467-017-01854-0
Assay systems  Chemical tools  Sensors and probes 

Phosphorylation of LAMP2A by p38 MAPK couples ER stress to chaperone-mediated autophagy OPEN
Wenming Li, Jinqiu Zhu, Juan Dou, Hua She, Kai Tao, Haidong Xu, Qian Yang & Zixu Mao

The endoplasmic reticulum (ER) and lysosome are central to cellular stress responses, but it is unclear how ER stress is signaled to lysosomes. Here the authors show that ER stress activates chaperone-mediated autophagy (CMA) via direct phosphorylation of the CMA receptor LAMP2A by the lysosomal p38 MAPK.

24 November 2017 | doi: 10.1038/s41467-017-01609-x
Chaperone-mediated autophagy  Endoplasmic reticulum  Lysosomes 

Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma OPEN
Mitsuteru Natsuizaka, Kelly A. Whelan, Shingo Kagawa, Koji Tanaka, Veronique Giroux, Prasanna M. Chandramouleeswaran, Apple Long, Varun Sahu, Douglas S. Darling, Jianwen Que, Yizeng Yang, Jonathan P. Katz, E. Paul Wileyto, Devraj Basu, Yoshiaki Kita, Shoji Natsugoe, Seiji Naganuma, Andres J. Klein-Szanto, J. Alan Diehl, Adam J. Bass et al.

Notch receptors can exert different roles in cancer. In this manuscript, the authors reveal that Notch1 activation and EMT promote tumor initiation and cancer cell heterogeneity in squamous cell carcinoma, while the repression of Notch3 by ZEB1 limits Notch1-induced differentiation, permitting Notch1-mediated EMT.

24 November 2017 | doi: 10.1038/s41467-017-01500-9
Cancer  Oesophageal cancer  Oncogenes 

Plasma cell survival in the absence of B cell memory OPEN
Erika Hammarlund, Archana Thomas, Ian J. Amanna, Lindsay A. Holden, Ov D. Slayden, Byung Park, Lina Gao & Mark K. Slifka

The long-term maintenance of antibody-secreting plasma cells and the requirement for memory B cells are unclear. Here, the authors show that plasma cells and the antibodies secreted are long-lived and maintained over a decade in the absence of memory B cells in non-human primates.

24 November 2017 | doi: 10.1038/s41467-017-01901-w
Experimental organisms  Plasma cells  Protein vaccines  Viral infection 

Elevated moisture stimulates carbon loss from mineral soils by releasing protected organic matter OPEN
Wenjuan Huang & Steven J. Hall

The effect of soil moisture on microbial activity and soil carbon storage remains unclear. Here, via Mollisol incubation experiments, the authors show elevated soil moisture can accelerate total carbon loss by facilitating microbial access to previously protected carbon, released following iron reduction.

24 November 2017 | doi: 10.1038/s41467-017-01998-z
Carbon cycle 

HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism OPEN
Weinan Du, Luchang Zhang, Adina Brett-Morris, Brittany Aguila, Janos Kerner, Charles L. Hoppel, Michelle Puchowicz, Dolors Serra, Laura Herrero, Brian I. Rini, Steven Campbell & Scott M. Welford

Clear cell renal cancers (ccRCC) display elevated intracellular lipid storage. Here the authors show that such lipid accumulation is due to the repression of carnitine palmitoyltransferase 1A (CPT1A) enzyme that impairs fatty acid (FA) transport into the mitochondrion resulting in reduced FA beta oxidation.

24 November 2017 | doi: 10.1038/s41467-017-01965-8
Cancer metabolism  Renal cell carcinoma 

High magnesium mobility in ternary spinel chalcogenides OPEN
Pieremanuele Canepa, Shou-Hang Bo, Gopalakrishnan Sai Gautam, Baris Key, William D. Richards, Tan Shi, Yaosen Tian, Yan Wang, Juchuan Li & Gerbrand Ceder

Low magnesium mobility in solids represents a significant obstacle to the development of Mg intercalation batteries. Here the authors show that substantial magnesium ion mobility can be achieved in close-packed ternary selenide spinel materials.

24 November 2017 | doi: 10.1038/s41467-017-01772-1
Batteries 

GABAA receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl-sensitive WNK1 kinase OPEN
Martin Heubl, Jinwei Zhang, Jessica C. Pressey, Sana Al Awabdh, Marianne Renner, Ferran Gomez-Castro, Imane Moutkine, Emmanuel Eugène, Marion Russeau, Kristopher T. Kahle, Jean Christophe Poncer & Sabine Lévi

GABAergic transmission regulates the K+-Cl co-transporter KCC2. Here the authors demonstrate that inhibitory transmission, via GABAA receptor and WNK signaling, regulates KCC2 expression in the membrane of hippocampal neurons.

24 November 2017 | doi: 10.1038/s41467-017-01749-0
Neurophysiology  Neurotransmitters  Transporters in the nervous system 

Benchmarking organic mixed conductors for transistors OPEN
Sahika Inal, George G. Malliaras & Jonathan Rivnay

Organic materials that support both electronic and ionic transport hold promise for applications in bioelectronics and energy storage. Here, Inal et al. use transistors to quantify the materials performance of organic mixed conductors in terms of the product of charge mobility and volumetric capacitance.

24 November 2017 | doi: 10.1038/s41467-017-01812-w
Electrical and electronic engineering  Electronic devices 

Josephson emission with frequency span 1–11 THz from small Bi2Sr2CaCu2O8+δ mesa structures OPEN
E. A. Borodianskyi & V. M. Krasnov

Small-area mesa structures made of layered Bi-2212 cuprates should have many advantages as terahertz oscillators but experimental realization of such oscillators has proven difficult. Here the authors report Josephson emission from small-but-high mesas, achieving a broad frequency span of 1–11 THz.

23 November 2017 | doi: 10.1038/s41467-017-01888-4
Lasers, LEDs and light sources  Superconducting devices  Terahertz optics 

Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2 OPEN
Manikandan Karuppasamy, Beata Kusmider, Taiana M. Oliveira, Christl Gaubitz, Manoel Prouteau, Robbie Loewith & Christiane Schaffitzel

Target of rapamycin (TOR) kinase operates within two distinct multiprotein complexes named TORC1 and TORC2. Here the authors report a cryo-EM structure of TORC2, establish its subunit organization, providing a rationale for TORC2’s rapamycin insensitivity and the mutually exclusive inclusion of Avo3/Rictor or Raptor within their respective TOR complex.

23 November 2017 | doi: 10.1038/s41467-017-01862-0
Cryoelectron microscopy  Kinases  TOR signalling 

Ultrafast bridge planarization in donor-π-acceptor copolymers drives intramolecular charge transfer OPEN
Palas Roy, Ajay Jha, Vineeth B. Yasarapudi, Thulasi Ram, Boregowda Puttaraju, Satish Patil & Jyotishman Dasgupta

Tracking and understanding charge transfer process is central yet challenging to designing efficient organic photovoltaics. Roy et al. monitor real-time structural changes in donor-π-acceptor polymer backbone, and enumerate the role of π-bridge torsions during intramolecular charge transfer.

23 November 2017 | doi: 10.1038/s41467-017-01928-z
Excited states  Solar cells 

Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening OPEN
Panpan Hou, Jodene Eldstrom, Jingyi Shi, Ling Zhong, Kelli McFarland, Yuan Gao, David Fedida & Jianmin Cui

KCNQ1 is a voltage-gated potassium channel that is important in cardiac and epithelial function. Here the authors present a mechanism for KCNQ1 activation and inactivation in which voltage sensor activation promotes pore opening more effectively in the intermediate open state than the fully open state, generating inactivation.

23 November 2017 | doi: 10.1038/s41467-017-01911-8
Arrhythmias  Kinetics 

Fusion guide RNAs for orthogonal gene manipulation with Cas9 and Cpf1 OPEN
Jiyeon Kweon, An-Hee Jang, Da-Eun Kim, Jin Wook Yang, Mijung Yoon, Ha Rim Shin, Jin-Soo Kim & Yongsub Kim

Cas9 and Cpf1 have both been adapted for genome engineering, editing and gene expression regulation. Here the authors design a fusion guide RNA that can interact with both proteins for multiple and orthogonal genome manipulation.

23 November 2017 | doi: 10.1038/s41467-017-01650-w
CRISPR-Cas9 genome editing  Genetic engineering  Genetic techniques 

The molecular basis of phosphite and hypophosphite recognition by ABC-transporters OPEN
Claudine Bisson, Nathan B. P. Adams, Ben Stevenson, Amanda A. Brindley, Despo Polyviou, Thomas S. Bibby, Patrick J. Baker, C. Neil Hunter & Andrew Hitchcock

Some bacteria can use inorganic phosphite and hypophosphite as sources of inorganic phosphorus. Here, the authors report crystal structures of the periplasmic proteins that bind these reduced phosphorus species and show that a P-H…π interaction between the ligand and binding site determines their specificity.

23 November 2017 | doi: 10.1038/s41467-017-01226-8
Biogeochemistry  Bioinformatics  Marine biology  X-ray crystallography 

Divergent synthesis of N-heterocycles via controllable cyclization of azido-diynes catalyzed by copper and gold OPEN
Wen-Bo Shen, Qing Sun, Long Li, Xin Liu, Bo Zhou, Juan-Zhu Yan, Xin Lu & Long-Wu Ye

Fused N-heterocycles are structural motifs observed in natural products and bioactive compounds. Here, the authors developed divergent copper- and gold-catalyzed oxidative cyclizations of diynes to two types of tricyclic N-heterocycles and rationalized the product selectivity by theoretical calculations.

23 November 2017 | doi: 10.1038/s41467-017-01853-1
Synthetic chemistry methodology  Reaction mechanisms 

Primer synthesis by a eukaryotic-like archaeal primase is independent of its Fe-S cluster OPEN
Sandro Holzer, Jiangyu Yan, Mairi L. Kilkenny, Stephen D. Bell & Luca Pellegrini

Primase is the specialised DNA-dependent RNA polymerase responsible for the initiation of DNA synthesis during DNA replication. Here the authors use a structural biology approach to identify the initiation site in the S. solfataricus PriSLX primase and to demonstrate that its Fe-S cluster is dispensable for primer synthesis.

23 November 2017 | doi: 10.1038/s41467-017-01707-w
DNA synthesis  Enzyme mechanisms  X-ray crystallography 

Experimentally simulating the dynamics of quantum light and matter at deep-strong coupling OPEN
N. K. Langford, R. Sagastizabal, M. Kounalakis, C. Dickel, A. Bruno, F. Luthi, D. J. Thoen, A. Endo & L. DiCarlo

Realising deep-strong coupling phenomena for interacting light-matter systems remains an experimental challenge. Here, Langford et al. employ a circuit quantum electrodynamics chip with moderate coupling between a resonator and transmon qubit to realise digital quantum simulation of deep-strong coupling dynamics.

23 November 2017 | doi: 10.1038/s41467-017-01061-x
Quantum simulation  Qubits  Superconducting devices 

A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells OPEN
Chris J. C. Johnston, Danielle J. Smyth, Ravindra B. Kodali, Madeleine P. J. White, Yvonne Harcus, Kara J. Filbey, James P. Hewitson, Cynthia S. Hinck, Alasdair Ivens, Andrea M. Kemter, Anna O. Kildemoes, Thierry Le Bihan, Dinesh C. Soares, Stephen M. Anderton, Thomas Brenn, Stephen J. Wigmore, Hannah V. Woodcock, Rachel C. Chambers, Andrew P. Hinck, Henry J. McSorley et al.

Heligmosomoides polygyrus can activate mammalian TGF-β signalling pathways, but how it does so is not known. Here the authors identify and isolate a H. polygyrus TFG-β mimic that can bind both mammalian TGF-β receptor subunits, activate Smad signalling and generate inducible regulatory T cells.

23 November 2017 | doi: 10.1038/s41467-017-01886-6
Immune evasion  Parasitic infection  Regulatory T cells  Transforming growth factor beta 

Repeated storage of respired carbon in the equatorial Pacific Ocean over the last three glacial cycles OPEN
A. W. Jacobel, J. F. McManus, R. F. Anderson & G. Winckler

During glacial periods the oceans stored carbon removed from the atmosphere, yet identifying precisely where that storage occurred remains challenging. Here, the authors show that the deep equatorial Pacific Ocean was a reservoir for respired carbon during glacial periods for at least the last 350 kyr.

23 November 2017 | doi: 10.1038/s41467-017-01938-x
Palaeoceanography  Palaeoclimate 

Structure of Rap1b bound to talin reveals a pathway for triggering integrin activation OPEN
Liang Zhu, Jun Yang, Thomas Bromberger, Ashley Holly, Fan Lu, Huan Liu, Kevin Sun, Sarah Klapproth, Jamila Hirbawi, Tatiana V. Byzova, Edward F. Plow, Markus Moser & Jun Qin

The transmembrane receptor integrin is activated by talin, but so far it has remained elusive how talin is recruited to the plasma membrane. Here, the authors identify the Rap1-mediated membrane-targeting mechanism for talin, present the Rap1b/talin-F0 structure and show that talin is a direct Rap1b effector.

23 November 2017 | doi: 10.1038/s41467-017-01822-8
Integrins  Solution-state NMR 

R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature OPEN
Fangfei Li, Junko Sawada & Masanobu Komatsu

Formation of the vascular lumen initiates the blood flow and it is crucial for tissue homeostasis. Here, Li et. al show that the R-Ras-Akt signaling axis is crucial for reparative angiogenesis in mice because it stabilizes the microtubule cytoskeleton in endothelial cells to promote endothelial lumen formation.

23 November 2017 | doi: 10.1038/s41467-017-01865-x
Cardiovascular biology  Growth factor signalling  Microtubules 

Skyrmion dynamics in a frustrated ferromagnetic film and current-induced helicity locking-unlocking transition OPEN
Xichao Zhang, Jing Xia, Yan Zhou, Xiaoxi Liu, Han Zhang & Motohiko Ezawa

Exploring the helicity-orbital coupling induced skyrmion properties is essential for the spintronic applications. Here the authors report the current controlled skyrmions and antiskyrmions dynamics with locking-unlocking helicity in frustrated magnets by including the dipole-dipole interaction in their model.

23 November 2017 | doi: 10.1038/s41467-017-01785-w
Ferromagnetism  Spintronics 

Chinese CO2 emission flows have reversed since the global financial crisis OPEN
Zhifu Mi, Jing Meng, Dabo Guan, Yuli Shan, Malin Song, Yi-Ming Wei, Zhu Liu & Klaus Hubacek

China has entered a new normal phase of economic development with a changing role in global trade. Here the authors show that emissions embodied in China’s exports declined from 2007 to 2012, while developing countries become the major destinations of China’s export emissions.

23 November 2017 | doi: 10.1038/s41467-017-01820-w
Business and industry  Climate-change mitigation  Economics 

Ultrafast non-radiative dynamics of atomically thin MoSe2  OPEN
Ming-Fu Lin, Vidya Kochat, Aravind Krishnamoorthy, Lindsay Bassman, Clemens Weninger, Qiang Zheng, Xiang Zhang, Amey Apte, Chandra Sekhar Tiwary, Xiaozhe Shen, Renkai Li, Rajiv Kalia, Pulickel Ajayan, Aiichiro Nakano, Priya Vashishta, Fuyuki Shimojo, Xijie Wang, David M. Fritz & Uwe Bergmann

Knowledge of the energy transfer pathways in transition metal dichalcogenides is essential to design efficient optoelectronic devices. Here, the authors use megaelectronvolt ultrafast electron diffraction to unveil the sub-picosecond lattice dynamics in MoSe2 following photoexcitation of charge carriers

23 November 2017 | doi: 10.1038/s41467-017-01844-2
Molecular dynamics  Two-dimensional materials 

Host STING-dependent MDSC mobilization drives extrinsic radiation resistance OPEN
Hua Liang, Liufu Deng, Yuzhu Hou, Xiangjiao Meng, Xiaona Huang, Enyu Rao, Wenxin Zheng, Helena Mauceri, Matthias Mack, Meng Xu, Yang-Xin Fu & Ralph R. Weichselbaum

Tumors often develop resistance to radiotherapy. Here the authors show that irradiation leads to a CCR2-dependent infiltration by myeloid derived suppressor cells that promote radio-resistance through inhibition of adaptive immune responses and that the use of CCR2 antibodies in mice reduces such resistance.

23 November 2017 | doi: 10.1038/s41467-017-01566-5
Cancer microenvironment  Immunosuppression 

Whole blood stabilization for the microfluidic isolation and molecular characterization of circulating tumor cells OPEN
Keith H. K. Wong, Shannon N. Tessier, David T. Miyamoto, Kathleen L. Miller, Lauren D. Bookstaver, Thomas R. Carey, Cleo J. Stannard, Vishal Thapar, Eric C. Tai, Kevin D. Vo, Erin S. Emmons, Haley M. Pleskow, Rebecca D. Sandlin, Lecia V. Sequist, David T. Ting, Daniel A. Haber, Shyamala Maheswaran, Shannon L. Stott & Mehmet Toner

The current FDA-approved whole blood stabilization method for circulating tumor cell (CTC) isolation suffers from RNA degradation. Here the authors combine hypothermic preservation and antiplatelet strategies to stabilize whole blood up to 72 h without compromising CTC yield and RNA integrity.

23 November 2017 | doi: 10.1038/s41467-017-01705-y
Cancer screening  Diagnostic markers  Laboratory techniques and procedures 

Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma OPEN
Martin Lauss, Marco Donia, Katja Harbst, Rikke Andersen, Shamik Mitra, Frida Rosengren, Maryem Salim, Johan Vallon-Christersson, Therese Törngren, Anders Kvist, Markus Ringnér, Inge Marie Svane & Göran Jönsson

Adoptive T cell therapy (ACT) has yielded high response rates in melanoma, however 50–60% of patients experience no clinical benefit. Here, the authors identify predictive biomarkers, high non-synonymous mutation and high expressed neoantigen load, that associate with clinical benefit in ACT melanoma patients.

23 November 2017 | doi: 10.1038/s41467-017-01460-0
Melanoma  Tumour immunology 

North Atlantic variability and its links to European climate over the last 3000 years OPEN
Paola Moffa-Sánchez & Ian R. Hall

The Labrador Sea drives the circulation of warm water around the North Atlantic’s subpolar gyre, yet the effect it has on European climate remains unclear. Here, the authors present a highly-resolved 3000 year-long reconstruction of gyre strength, and link gyre weakening to European cold periods.

23 November 2017 | doi: 10.1038/s41467-017-01884-8
Palaeoceanography  Palaeoclimate 

Scallop genome reveals molecular adaptations to semi-sessile life and neurotoxins OPEN
Yuli Li, Xiaoqing Sun, Xiaoli Hu, Xiaogang Xun, Jinbo Zhang, Ximing Guo, Wenqian Jiao, Lingling Zhang, Weizhi Liu, Jing Wang, Ji Li, Yan Sun, Yan Miao, Xiaokang Zhang, Taoran Cheng, Guoliang Xu, Xiaoteng Fu, Yangfan Wang, Xinran Yu, Xiaoting Huang et al.

Bivalve molluscs have evolved various characteristics to adapt to benthic filter-feeding. Here, Li et al investigate the genome, transcriptomes and proteomes of scallop Chlamys farreri, revealing evidences of molecular adaptations to semi-sessile life and neurotoxins.

23 November 2017 | doi: 10.1038/s41467-017-01927-0
Genome  Molecular evolution  Next-generation sequencing 

Glucocorticoid-induced phosphorylation by CDK9 modulates the coactivator functions of transcriptional cofactor GRIP1 in macrophages OPEN
David A. Rollins, Joubert B. Kharlyngdoh, Maddalena Coppo, Bowranigan Tharmalingam, Sanda Mimouna, Ziyi Guo, Maria A. Sacta, Miles A. Pufall, Robert P. Fisher, Xiaoyu Hu, Yurii Chinenov & Inez Rogatsky

Glucocorticoid reduces inflammation by both inducing anti-inflammatory genes and suppressing pro-inflammatory genes, but how these two functions are dictated is unclear. Here the authors show that phosphorylated glucocorticoid receptor-interacting protein 1 (GRIP1) serves as a coactivator for this response in macrophage.

23 November 2017 | doi: 10.1038/s41467-017-01569-2
Immunosuppression  Inflammation  Monocytes and macrophages  Transcription 

The influence of the solid to plasma phase transition on the generation of plasma instabilities OPEN
E. Kaselouris, V. Dimitriou, I. Fitilis, A. Skoulakis, G. Koundourakis, E. L. Clark, Μ. Bakarezos, I. K. Nikolos, N. A. Papadogiannis & M. Tatarakis

Exploring the plasma processes in the pre-plasma state that lead to instabilities is challenging. Here the authors probe the evolution of the plasma phase change and the instabilities in plasma created by an exploding copper wire in Z-pinch geometry using shadowgraphy.

23 November 2017 | doi: 10.1038/s41467-017-02000-6
Characterization and analytical techniques  Plasma physics 

MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance OPEN
Amy S. Farrell, Meghan Morrison Joly, Brittany L. Allen-Petersen, Patrick J. Worth, Christian Lanciault, David Sauer, Jason Link, Carl Pelz, Laura M. Heiser, Jennifer P. Morton, Nathiya Muthalagu, Megan T. Hoffman, Sara L. Manning, Erica D. Pratt, Nicholas D. Kendsersky, Nkolika Egbukichi, Taylor S. Amery, Mary C. Thoma, Zina P. Jenny, Andrew D. Rhim et al.

Neuroendocrine differentiation of epithelial tumor cells can contribute to cancer cell resistance and survival. Here, the authors show that dysregulated c-Myc promotes neuroendocrine differentiation in pancreatic ductal adenocarcinoma, leading to poor survival and chemoresistance.

23 November 2017 | doi: 10.1038/s41467-017-01967-6
Pancreatic cancer  Tumour heterogeneity 

Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function OPEN
Georgia Balsevich, Alexander S. Häusl, Carola W. Meyer, Stoyo Karamihalev, Xixi Feng, Max L. Pöhlmann, Carine Dournes, Andres Uribe-Marino, Sara Santarelli, Christiana Labermaier, Kathrin Hafner, Tianqi Mao, Michaela Breitsamer, Marily Theodoropoulou, Christian Namendorf, Manfred Uhr, Marcelo Paez-Pereda, Gerhard Winter, Felix Hausch, Alon Chen et al.

Stress is recognized as risk factor for the development of type 2 diabetes. Here Balsevich et al. show that the stress responsive co-chaperone FKBP5 regulates glucose metabolism in mice by modulating AS160 phosphorylation, glucose transporter expression and muscle glucose uptake.

23 November 2017 | doi: 10.1038/s41467-017-01783-y
Obesity  Stress and resilience  Type 2 diabetes 

Visual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types OPEN
Vincent van Unen, Thomas Höllt, Nicola Pezzotti, Na Li, Marcel J. T. Reinders, Elmar Eisemann, Frits Koning, Anna Vilanova & Boudewijn P. F. Lelieveldt

Single cell profiling yields high dimensional data of very large numbers of cells, posing challenges of visualization and analysis. Here the authors introduce a method for analysis of mass cytometry data that can handle very large datasets and allows their intuitive and hierarchical exploration.

23 November 2017 | doi: 10.1038/s41467-017-01689-9
Computational biology and bioinformatics  Flow cytometry  Immunology 

Generation of interspecies limited chimeric nephrons using a conditional nephron progenitor cell replacement system OPEN
S. Yamanaka, S. Tajiri, T. Fujimoto, K. Matsumoto, S. Fukunaga, B. S. Kim, H. J. Okano & T. Yokoo

The transplantation of tissue-specific progenitor cells may be an approach in organ regeneration. Here the authors show that the nephron progenitor population of a developing mouse kidney, when ablated, can be replaced by exogenously supplied rat nephron progenitors, generating interspecies nephrons.

23 November 2017 | doi: 10.1038/s41467-017-01922-5
Differentiation  Nephrons  Organogenesis 

Switchable photovoltaic windows enabled by reversible photothermal complex dissociation from methylammonium lead iodide OPEN
Lance M. Wheeler, David T. Moore, Rachelle Ihly, Noah J. Stanton, Elisa M. Miller, Robert C. Tenent, Jeffrey L. Blackburn & Nathan R. Neale

Conventional smart windows with tunable transparency are based on electrochromic systems that consumes energy. Here Wheeler et al. demonstrate a halide perovskite based photo-switchable window that dynamically responds to sunlight and change colors via reversible phase transitions.

23 November 2017 | doi: 10.1038/s41467-017-01842-4
Devices for energy harvesting  Energy harvesting  Materials for devices  Solar cells 

Assembly of CRISPR ribonucleoproteins with biotinylated oligonucleotides via an RNA aptamer for precise gene editing OPEN
Jared Carlson-Stevermer, Amr A. Abdeen, Lucille Kohlenberg, Madelyn Goedland, Kaivalya Molugu, Meng Lou & Krishanu Saha

Using CRISPR to write specific genetic sequences can sometimes be difficult due to the preference of mammalian cells to repair breaks using NHEJ. Here the authors form nanoparticles to localize the template sequence to the nuclease, shifting repair in favor of HDR.

23 November 2017 | doi: 10.1038/s41467-017-01875-9
CRISPR-Cas9 genome editing  Genetic engineering 

Complex three-dimensional self-assembly in proxies for atmospheric aerosols OPEN
C. Pfrang, K. Rastogi, E. R. Cabrera-Martinez, A. M. Seddon, C. Dicko, A. Labrador, T. S. Plivelic, N. Cowieson & A. M. Squires

Nearly all atmospheric aerosols contain surface-active organic compounds; however, the nature of how they arrange remains poorly understood. Here, the authors show that fatty acids in atmospheric aerosol proxies self-assemble into highly ordered, viscous 3D nanostructures that undergo changes upon exposure to humidity and ozone.

23 November 2017 | doi: 10.1038/s41467-017-01918-1
Atmospheric chemistry  Characterization and analytical techniques  Molecular self-assembly 

T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity OPEN
Daniela Schmid, Chun Gwon Park, Christina A. Hartl, Nikita Subedi, Adam N. Cartwright, Regina Bou Puerto, Yiran Zheng, James Maiarana, Gordon J. Freeman, Kai W. Wucherpfennig, Darrell J. Irvine & Michael S. Goldberg

Targeted delivery of immunomodulatory compounds to defined subsets of endogenous immune cells may improve the efficacy of combination immunotherapies. Here, the authors use PD-1-targeting nanoparticles containing a TGFβ inhibitor or a TLR7/8 agonist to deliver these payloads to T cells or via T cells to the tumor microenvironment, respectively, leading to anti-tumor efficacy in vivo.

23 November 2017 | doi: 10.1038/s41467-017-01830-8
Cancer immunotherapy  Nanoparticles 

Genome-wide identification and differential analysis of translational initiation OPEN
Peng Zhang, Dandan He, Yi Xu, Jiakai Hou, Bih-Fang Pan, Yunfei Wang, Tao Liu, Christel M. Davis, Erik A. Ehli, Lin Tan, Feng Zhou, Jian Hu, Yonghao Yu, Xi Chen, Tuan M. Nguyen, Jeffrey M. Rosen, David H. Hawke, Zhe Ji & Yiwen Chen

Translation initiation sequencing (TI-seq) has revealed unexpected diversity in protein isoforms. Here, Zhang et al. present Ribo-TISH, a computational toolkit that can detect and compare TIs across conditions and improve open reading frame prediction from different types of ribosome profiling data.

23 November 2017 | doi: 10.1038/s41467-017-01981-8
Computational biology and bioinformatics  Functional genomics  Long non-coding RNAs  Translation 

Simulating quantum light propagation through atomic ensembles using matrix product states OPEN
Marco T. Manzoni, Darrick E. Chang & James S. Douglas

Numerical simulation of light propagation through 1D atomic systems in the many-body limit rapidly saturates hardware capabilities. Here, the authors tackle the problem by mapping the dynamics to an open 1D interacting spin system and solving it using the matrix product state ansatz.

23 November 2017 | doi: 10.1038/s41467-017-01416-4
Nonlinear optics  Quantum optics  Single photons and quantum effects  Slow light 

Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations OPEN
Wilton B. Williams, Jinsong Zhang, Chuancang Jiang, Nathan I. Nicely, Daniela Fera, Kan Luo, M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Thomas B. Kepler, Akshaya Ramesh, Kevin Wiehe, James A. Holland, Todd Bradley, Nathan Vandergrift, Kevin O. Saunders, Robert Parks, Andrew Foulger, Shi-Mao Xia, Mattia Bonsignori et al.

An efficient HIV-1 vaccine will likely depend on eliciting broadly neutralizing antibodies (bnAb). Here the authors analyze the B cell repertoire in macaques and knock-in mice in response to sequential immunization with Env variants that induce a bnAb targeting the CD4-binding site of Env in a HIV-1 infected individual.

23 November 2017 | doi: 10.1038/s41467-017-01336-3
B-cell receptor  HIV infections  Peripheral tolerance  Protein vaccines 

Receptor-binding loops in alphacoronavirus adaptation and evolution OPEN
Alan H. M. Wong, Aidan C. A. Tomlinson, Dongxia Zhou, Malathy Satkunarajah, Kevin Chen, Chetna Sharon, Marc Desforges, Pierre J. Talbot & James M. Rini

Coronaviruses have a relatively high mutation rate, potentially allowing fast adaptation to changing pressures. Here, Wong et al. provide the structure of the receptor-binding domain (RBD) of the human coronavirus HCoV-229E and its receptor and analyze the evolution of the RBD over the past 50 years.

23 November 2017 | doi: 10.1038/s41467-017-01706-x
Viral immune evasion  Viral membrane fusion  Virus structures  X-ray crystallography 

Quantifying protein densities on cell membranes using super-resolution optical fluctuation imaging OPEN
Tomáš Lukeš, Daniela Glatzová, Zuzana Kvíčalová, Florian Levet, Aleš Benda, Sebastian Letschert, Markus Sauer, Tomáš Brdička, Theo Lasser & Marek Cebecauer

The ability to quantify the organization of cell membrane molecules is limited by the density of labeling and experimental conditions. Here, the authors use super-resolution optical fluctuation (SOFI) for molecular density and clustering analyses, and investigate nanoscale distribution of CD4 glycoprotein.

23 November 2017 | doi: 10.1038/s41467-017-01857-x
Fluorescence imaging  Imaging the immune system  Super-resolution microscopy 

An extracellular matrix-related prognostic and predictive indicator for early-stage non-small cell lung cancer OPEN
Su Bin LIM, Swee Jin TAN, Wan-Teck LIM & Chwee Teck LIM

Prognosis and prediction of adjuvant chemotherapy response in non-small cell lung cancer can have significant clinical impact. Here, the authors show that differential expression of a 29 extracellular matrix gene indicator, EPPI, can predict patient outcome.

23 November 2017 | doi: 10.1038/s41467-017-01430-6
Predictive medicine  Tumour biomarkers 

Heme enables proper positioning of Drosha and DGCR8 on primary microRNAs OPEN
Alexander C. Partin, Tri D. Ngo, Emily Herrell, Byung-Cheon Jeong, Gary Hon & Yunsun Nam

Drosha and DGCR8 constitute the core Microprocessor complex, which processes primary microRNAs (pri-miRs) into mature microRNAs. Here the authors show that heme is essential for the proper processing of pri-miRs by Drosha-DGCR8, and the molecular mechanism by which heme enhances processing fidelity.

23 November 2017 | doi: 10.1038/s41467-017-01713-y
Enzyme mechanisms  miRNAs  RNA 
 
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  Latest Errata    
 
Erratum: Modulation of mRNA and lncRNA expression dynamics by the Set2–Rpd3S pathway OPEN
Ji Hyun Kim, Bo Bae Lee, Young Mi Oh, Chenchen Zhu, Lars M. Steinmetz, Yookyeong Lee, Wan Kyu Kim, Sung Bae Lee, Stephen Buratowski & TaeSoo Kim
29 November 2017 | doi: 10.1038/ncomms16122
Histone post-translational modifications  Long non-coding RNAs  Transcription 

Erratum: The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites OPEN
Kyungsoo Ha, Chengxian Ma, Han Lin, Lichun Tang, Zhusheng Lian, Fang Zhao, Ju-Mei Li, Bei Zhen, Huadong Pei, Suxia Han, Marcos Malumbres, Jianping Jin, Huan Chen, Yongxiang Zhao, Qing Zhu & Pumin Zhang
29 November 2017 | doi: 10.1038/ncomms16156
DNA damage response  Double-strand DNA breaks 

Erratum: Cooling a mechanical resonator with nitrogen-vacancy centres using a room temperature excited state spin–strain interaction OPEN
E. R. MacQuarrie, M. Otten, S. K. Gray & G. D. Fuchs
29 November 2017 | doi: 10.1038/ncomms16166
Optical properties of diamond  Magnetic properties and materials  Quantum mechanics 
 
  Latest Corrigenda    
 
Corrigendum: Insufficient antibody validation challenges oestrogen receptor beta research OPEN
Sandra Andersson, Mårten Sundberg, Nusa Pristovsek, Ahmed Ibrahim, Philip Jonsson, Borbala Katona, Carl-Magnus Clausson, Agata Zieba, Margareta Ramström, Ola Söderberg, Cecilia Williams & Anna Asplund
29 November 2017 | doi: 10.1038/ncomms16164
Breast cancer  Immunohistochemistry  Tumour biomarkers 

Corrigendum: Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state OPEN
Iebe Rossey, Morgan S. A. Gilman, Stephanie C. Kabeche, Koen Sedeyn, Daniel Wrapp, Masaru Kanekiyo, Man Chen, Vicente Mas, Jan Spitaels, José A. Melero, Barney S. Graham, Bert Schepens, Jason S. McLellan & Xavier Saelens
29 November 2017 | doi: 10.1038/ncomms16165
Antibody fragment therapy  Virus structures  X-ray crystallography 

Corrigendum: High-rate aluminium yolk-shell nanoparticle anode for Li-ion battery with long cycle life and ultrahigh capacity OPEN
Sa Li, Junjie Niu, Yu Cheng Zhao, Kang Pyo So, Chao Wang, Chang An Wang & Ju Li
29 November 2017 | doi: 10.1038/ncomms16174
Batteries  Biophysical chemistry  Nanoparticles  Synthesis and processing 
 
 

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