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Nature Communications - 14 March 2018

Nature Communications

Princeton University, Princeton Institute for the Science and Technology of Materials (PRISM), Nature Communications, Nature Materials, Nature Structural & Molecular Biology present:

Princeton - Nature Conference: Frontiers in Electron Microscopy for the Physical and Life Sciences
July 11-13, 2018, Princeton University, Princeton, NJ, USA

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14 March 2018 
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Dark zone of the Greenland Ice Sheet controlled by distributed biologically-active impurities OPEN
Jonathan C. Ryan, Alun Hubbard, Marek Stibal, Tristram D. Irvine-Fynn, Joseph Cook, Laurence C. Smith, Karen Cameron & Jason Box

The surface types that comprise the dark zone of the Greenland Ice Sheet, an area of bare ice with low albedo, are unknown. Here, the authors use UAV imagery to show that, during the melt-season, biologically active surface impurities are responsible for spatial albedo patterns and the dark zone itself.

14 March 2018 | doi: 10.1038/s41467-018-03353-2
Cryospheric science 

The preprophase band-associated kinesin-14 OsKCH2 is a processive minus-end-directed microtubule motor OPEN
Kuo-Fu Tseng, Pan Wang, Yuh-Ru Julie Lee, Joel Bowen, Allison M. Gicking, Lijun Guo, Bo Liu & Weihong Qiu

Land plants lack the cytoplasmic dynein motor in fungi and animals that shows processive minus-end-directed motility on microtubules. Here the authors demonstrate that land plants have evolved novel processive minus-end-directed kinesin-14 motors that likely compensate for the absence of dynein.

14 March 2018 | doi: 10.1038/s41467-018-03480-w
Kinesin  Motor protein function  Plant cytoskeleton  Single-molecule biophysics 

Magnon detection using a ferroic collinear multilayer spin valve OPEN
Joel Cramer, Felix Fuhrmann, Ulrike Ritzmann, Vanessa Gall, Tomohiko Niizeki, Rafael Ramos, Zhiyong Qiu, Dazhi Hou, Takashi Kikkawa, Jairo Sinova, Ulrich Nowak, Eiji Saitoh & Mathias Kläui

The Joule heating free magnon spintronics advances conventional electronics but demands more magnon-based logic operations. Here the authors achieved the magnon spin valve functionality in a YIG/CoO/Co structure where the amplitude of transmitted magnon from the YIG layer is dependent on the relative alignment of the YIG and Co magnetization.

14 March 2018 | doi: 10.1038/s41467-018-03485-5
Ferromagnetism  Spintronics 

Predicting the spatiotemporal diversity of seizure propagation and termination in human focal epilepsy OPEN
Timothée Proix, Viktor K. Jirsa, Fabrice Bartolomei, Maxime Guye & Wilson Truccolo

A major goal of epilepsy research is understanding the spatiotemporal dynamics of seizure. Here, the authors extend the Epileptor neural mass model into a neural field model, in order to provide a unified and patient-specific model of seizure initiation, propagation, and termination.

14 March 2018 | doi: 10.1038/s41467-018-02973-y
Dynamical systems  Epilepsy  Network models 

Chemo-photothermal therapy combination elicits anti-tumor immunity against advanced metastatic cancer OPEN
Jutaek Nam, Sejin Son, Lukasz J. Ochyl, Rui Kuai, Anna Schwendeman & James J. Moon

Photothermal therapy (PTT) for cancer treatment is currently limited to local, accessible, tumors. Here the authors show that PTT combination with chemotherapy, by stimulating an immune response, is effective against distant tumors and establishes immune memory, thus providing a strategy to target metastatic disease.

14 March 2018 | doi: 10.1038/s41467-018-03473-9
Biomedical engineering  Cancer immunotherapy  Drug delivery 

Micro-scale fusion in dense relativistic nanowire array plasmas OPEN
Alden Curtis, Chase Calvi, James Tinsley, Reed Hollinger, Vural Kaymak, Alexander Pukhov, Shoujun Wang, Alex Rockwood, Yong Wang, Vyacheslav N. Shlyaptsev & Jorge J. Rocca

Neutron beams are useful studying fundamental physics problems, fusion process and material properties. Here the authors use intense laser irradiation of deuterated nanowire array targets to create high energy density plasmas capable of efficient generation of ultrafast neutron pulses.

14 March 2018 | doi: 10.1038/s41467-018-03445-z
Laser-produced plasmas  Nanowires  Plasma-based accelerators  Ultrafast lasers 

Shallow very-low-frequency earthquakes accompany slow slip events in the Nankai subduction zone OPEN
Masaru Nakano, Takane Hori, Eiichiro Araki, Shuichi Kodaira & Satoshi Ide

Slow earthquakes are now increasingly recognised to occur at plate boundaries globally. Here, the authors examine seafloor observational data from the Nankai trough and find that very-low-frequency events and slow-slip events frequently occur together and share the same common source fault.

14 March 2018 | doi: 10.1038/s41467-018-03431-5
Geodynamics  Seismology 

The choroid plexus is an important circadian clock component OPEN
Jihwan Myung, Christoph Schmal, Sungho Hong, Yoshiaki Tsukizawa, Pia Rose, Yong Zhang, Michael J. Holtzman, Erik De Schutter, Hanspeter Herzel, Grigory Bordyugov & Toru Takumi

The suprachiasmatic nucleus (SCN) has been thought of as the master circadian clock, but peripheral circadian clocks do exist. Here, the authors show that the choroid plexus displays oscillations more robust than the SCN and that can be described as a Poincaré oscillator with negative twist.

14 March 2018 | doi: 10.1038/s41467-018-03507-2
Circadian mechanisms  Oscillators 

Improving atomic displacement and replacement calculations with physically realistic damage models OPEN
Kai Nordlund, Steven J. Zinkle, Andrea E. Sand, Fredric Granberg, Robert S. Averback, Roger Stoller, Tomoaki Suzudo, Lorenzo Malerba, Florian Banhart, William J. Weber, Francois Willaime, Sergei L. Dudarev & David Simeone

The Norgett−Robinson−Torrens displacements per atom model is the benchmark to assess radiation damage in metals but has well-known limitations. Here, the authors use molecular dynamics to introduce material-specific modifications to describe radiation damage more realistically.

14 March 2018 | doi: 10.1038/s41467-018-03415-5
Metals and alloys  Nuclear physics  Theory and computation 

Intermembrane crosstalk drives inner-membrane protein organization in Escherichia coli OPEN
Patrice Rassam, Kathleen R. Long, Renata Kaminska, David J. Williams, Grigorios Papadakos, Christoph G. Baumann & Colin Kleanthous

Outer membrane proteins (OMPs) in Gram-negative bacteria have restricted lateral mobility. Here, Rassam et al. show that the bacteriocin ColE9, via its interactions with OMPs, imposes this restricted mobility on the inner membrane proteins of the Tol-Pal complex.

14 March 2018 | doi: 10.1038/s41467-018-03521-4
Biological fluorescence  Cellular microbiology  Membrane structure and assembly 

Next generation histology methods for three-dimensional imaging of fresh and archival human brain tissues OPEN
Hei Ming Lai, Alan King Lun Liu, Harry Ho Man Ng, Marc H. Goldfinger, Tsz Wing Chau, John DeFelice, Bension S. Tilley, Wai Man Wong, Wutian Wu & Steve M. Gentleman

Current available tissue clearing techniques are mostly used for rodent tissues. Here, the authors develop OPTIClear solution for fresh and archival human brain tissue clearing and establish associated protocols for three-dimensional histological investigations.

14 March 2018 | doi: 10.1038/s41467-018-03359-w
Immunohistochemistry  Neurology  Neuroscience  Optical imaging 

Structures of Teneurin adhesion receptors reveal an ancient fold for cell-cell interaction OPEN
Verity A. Jackson, Dimphna H. Meijer, Maria Carrasquero, Laura S. van Bezouwen, Edward D. Lowe, Colin Kleanthous, Bert J. C. Janssen & Elena Seiradake

Teneurins are cell-cell adhesion receptors that evolved through horizontal gene transfer in which a bacterial YD-repeat protein fused to a eukaryotic receptor. Here the authors present crystallographic and cryo-EM structures of two Teneurins, revealing an ancient YD-repeat protein super-fold.

14 March 2018 | doi: 10.1038/s41467-018-03460-0
Bacterial toxins  Development of the nervous system  Electron microscopy  X-ray crystallography 

Internal climate variability and projected future regional steric and dynamic sea level rise OPEN
Aixue Hu & Susan C. Bates

As the global climate becomes warmer, the associated rising sea level could pose significant threats to island and coastal communities. Here the authors show that internal climate variability plays a key role in determining this sea level rise, especially in the next few decades.

14 March 2018 | doi: 10.1038/s41467-018-03474-8
Physical oceanography  Physics 

The underappreciated potential of peatlands in global climate change mitigation strategies OPEN
J. Leifeld & L. Menichetti

Human activity, such as draining and mining of peatlands, is transforming these long-term carbon sinks into sources. Here, the authors assess current and future greenhouse gas (GHG) emissions from degrading peatlands and estimate the magnitude of potential GHG savings that could be achieved by restoring them.

14 March 2018 | doi: 10.1038/s41467-018-03406-6
Biogeochemistry  Carbon cycle 

Clinically compliant spatial and temporal imaging of chimeric antigen receptor T-cells OPEN
Nia Emami-Shahri, Julie Foster, Roxana Kashani, Patrycja Gazinska, Celia Cook, Jane Sosabowski, John Maher & Sophie Papa

Adoptive transfer of chimeric antigen receptor (CAR) T cells has shown promising anticancer results in clinical trials. Here the authors use the human sodium iodide symporter (hNIS) as a reporter gene to image human CAR T cells in cancer-bearing mice using broadly available tracers and imaging platforms.

14 March 2018 | doi: 10.1038/s41467-018-03524-1
Cancer imaging  Cancer immunotherapy 

Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal OPEN
Shantisree Sandeepani Rayagiri, Daniele Ranaldi, Alexander Raven, Nur Izzah Farhana Mohamad Azhar, Olivier Lefebvre, Peter S Zammit & Anne-Gaëlle Borycki

Extracellular matrix (ECM) remodelling is thought to have effects on muscle stem cells that support muscle homeostasis. Here the authors show ECM remodeling controls satellite cell self-renewal through deposition of laminin-α1 into the satellite cell niche.

14 March 2018 | doi: 10.1038/s41467-018-03425-3
Muscle stem cells  Self-renewal 

Crystal structure of undecaprenyl-pyrophosphate phosphatase and its role in peptidoglycan biosynthesis OPEN
Meriem El Ghachi, Nicole Howe, Chia-Ying Huang, Vincent Olieric, Rangana Warshamanage, Thierry Touzé, Dietmar Weichert, Phillip J. Stansfeld, Meitian Wang, Fred Kerff & Martin Caffrey

Bacterial cell wall components are assembled in a transmembrane cycle that involves the membrane integral pyrophosphorylase, BacA. Here the authors solve the crystal structure of BacA which shows an interdigitated inverted topology repeat that hints towards a flippase function for BacA.

14 March 2018 | doi: 10.1038/s41467-018-03477-5
Biochemistry  Structural biology  X-ray crystallography 

Accumbens dopamine D2 receptors increase motivation by decreasing inhibitory transmission to the ventral pallidum OPEN
Eduardo F. Gallo, Jozsef Meszaros, Jeremy D. Sherman, Muhammad O. Chohan, Eric Teboul, Claire S. Choi, Holly Moore, Jonathan A. Javitch & Christoph Kellendonk

Dopamine D2 receptor activity in the nucleus accumbens is associated with regulation of motivated responding. Here the authors show that overexpression of D2 receptors specifically in ventral striatal projection neurons leads to an increase in the willingness to work by reducing inhibitory transmission to ventral pallidal neurons.

14 March 2018 | doi: 10.1038/s41467-018-03272-2
Cellular neuroscience  Motivation  Neural circuits 

A non-conserved amino acid variant regulates differential signalling between human and mouse CD28 OPEN
Nicla Porciello, Paola Grazioli, Antonio F. Campese, Martina Kunkl, Silvana Caristi, Marta Mastrogiovanni, Michela Muscolini, Francesca Spadaro, Cédric Favre, Jacques A. Nunès, Aldo Borroto, Balbino Alarcon, Isabella Screpanti & Loretta Tuosto

CD28 transmits co-stimulatory signals for the activation of both mouse and human T cells, but in vivo hyperactivation of CD28 has opposite effects on system immunity. Here, the authors show that a single amino acid difference between mouse and human CD28 dictates this function distinction via differential recruitment of Nck.

14 March 2018 | doi: 10.1038/s41467-018-03385-8
Autoimmune diseases  CD4-positive T cells  NF-kappaB  Signal transduction 

Cascading lake drainage on the Greenland Ice Sheet triggered by tensile shock and fracture OPEN
Poul Christoffersen, Marion Bougamont, Alun Hubbard, Samuel H. Doyle, Shane Grigsby & Rickard Pettersson

Lakes on the Greenland Ice Sheet transfer water to the bed when they drain, but the impact is unknown. Here, the authors use a 3D model to show that lakes drain when fractures form, causing a chain reaction in which cascading lake drainages extend inland and deliver water to previously isolated regions of the bed.

14 March 2018 | doi: 10.1038/s41467-018-03420-8
Cryospheric science  Environmental impact 

Surface passivation engineering strategy to fully-inorganic cubic CsPbI3 perovskites for high-performance solar cells OPEN
Bo Li, Yanan Zhang, Lin Fu, Tong Yu, Shujie Zhou, Luyuan Zhang & Longwei Yin

Inorganic cesium lead iodide perovskite is inherently more stable than the hybrid perovskites but it undergoes phase transition that degrades the solar cell performance. Here Li et al. stabilize it with poly-vinylpyrrolidone and obtain high efficiency of 10.74% with excellent thermal and moisture stability.

14 March 2018 | doi: 10.1038/s41467-018-03169-0
Photovoltaics  Solar cells 

Electrochemically active bacteria sense electrode potentials for regulating catabolic pathways OPEN
Atsumi Hirose, Takuya Kasai, Motohide Aoki, Tomonari Umemura, Kazuya Watanabe & Atsushi Kouzuma

Whether electrochemically active bacteria (EAB) can gain energy according to electrode potentials is still unclear. Here, the authors show through transcriptome and deletion mutant analyses that EAB can sense electrode potentials by the Arc system and activate NADH-dependent catabolic pathway to generate ATP.

14 March 2018 | doi: 10.1038/s41467-018-03416-4
Applied microbiology  Bacterial physiology  Microarray analysis 

Spin-liquid-like state in a spin-1/2 square-lattice antiferromagnet perovskite induced by d10d0 cation mixing OPEN
O. Mustonen, S. Vasala, E. Sadrollahi, K. P. Schmidt, C. Baines, H. C. Walker, I. Terasaki, F. J. Litterst, E. Baggio-Saitovitch & M. Karppinen

Quantum spin liquids are predicted to form in frustrated square lattice magnets but this has been difficult to verify experimentally. Here the authors show that cation mixing in the square perovskite Sr2Cu(Te0.5W0.5)O6 can be used to tune it into the spin liquid regime.

14 March 2018 | doi: 10.1038/s41467-018-03435-1
Magnetic properties and materials  Materials chemistry 

Hydrogen peroxide positively regulates brassinosteroid signaling through oxidation of the BRASSINAZOLE-RESISTANT1 transcription factor OPEN
Yanchen Tian, Min Fan, Zhaoxia Qin, Hongjun Lv, Minmin Wang, Zhe Zhang, Wenying Zhou, Na Zhao, Xiaohui Li, Chao Han, Zhaojun Ding, Wenfei Wang, Zhi-Yong Wang & Ming-Yi Bai

Hydrogen peroxide and brassinosteroids (BR) both regulate plant development and stress responses. Here Tian et al. show that hydrogen peroxide can trigger oxidation of the BR-responsive BZR1 transcription factor and promote its transcriptional activity, thereby linking BR and redox signaling.

14 March 2018 | doi: 10.1038/s41467-018-03463-x
Brassinosteroid  Plant signalling  Post-translational modifications 

Circular DNA elements of chromosomal origin are common in healthy human somatic tissue OPEN
Henrik Devitt Møller, Marghoob Mohiyuddin, Iñigo Prada-Luengo, M. Reza Sailani, Jens Frey Halling, Peter Plomgaard, Lasse Maretty, Anders Johannes Hansen, Michael P. Snyder, Henriette Pilegaard, Hugo Y. K. Lam & Birgitte Regenberg

Somatic cells can accumulate structural variations such as deletions. Here, Møller et al. show that normal human cells generate large extrachromosomal circular DNAs (eccDNAs), most likely the products of excised DNA, that can be transcriptionally active and, thus, may have phenotypic consequences.

14 March 2018 | doi: 10.1038/s41467-018-03369-8
DNA damage and repair  Genomic instability  Structural variation 

Compression force sensing regulates integrin αIIbβ3 adhesive function on diabetic platelets OPEN
Lining Ju, James D. McFadyen, Saheb Al-Daher, Imala Alwis, Yunfeng Chen, Lotte L. Tønnesen, Sophie Maiocchi, Brianna Coulter, Anna C. Calkin, Eric I. Felner, Neale Cohen, Yuping Yuan, Simone M. Schoenwaelder, Mark E. Cooper, Cheng Zhu & Shaun P. Jackson

Diabetes is associated with an increased thrombotic response, but the mechanism is unknown. Here the authors demonstrate that compressive force activates integrin αIIbβ3 on discoid diabetic platelets and that platelet aggregates can be eliminated by PI 3-kinase inhibition, but not by anti-thrombotics aspirin or clopidogrel.

14 March 2018 | doi: 10.1038/s41467-018-03430-6
Cardiovascular diseases  Integrins  Mechanisms of disease  Platelets 

Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression OPEN
Lingdi Zhang, Hengbo Zhou, Xueni Li, Rebecca L Vartuli, Michael Rowse, Yongna Xing, Pratyaydipta Rudra, Debashis Ghosh, Rui Zhao & Heide L Ford

Eya proteins are characterised by phosphatase activity associated with both the evolutionary conserved region and the less conserved N-terminal domain (NTD). Here the authors show that NTD mediates the interaction with PP2A and regulates c-Myc phosphorylation and stability, potentially switching PP2A from a tumour suppressor to an oncogene.

13 March 2018 | doi: 10.1038/s41467-018-03327-4
Breast cancer 

Functionally distinct and selectively phosphorylated GPCR subpopulations co-exist in a single cell OPEN
Ao Shen, Madeline Nieves-Cintron, Yawen Deng, Qian Shi, Dhrubajyoti Chowdhury, Jinyi Qi, Johannes W. Hell, Manuel F. Navedo & Yang K. Xiang

β2-adrenergic receptor (β2AR) can be phosphorylated by G protein receptor kinases and second messenger-dependent kinases. Here, the authors demonstrate that these phosphorylation events are specific to functionally distinct and spatially segregated subpopulations of β2AR that co-exist in a single cell.

13 March 2018 | doi: 10.1038/s41467-018-03459-7
Cellular neuroscience  G protein-coupled receptors  Phosphorylation  Single-molecule biophysics 

GATA3 zinc finger 2 mutations reprogram the breast cancer transcriptional network OPEN
Motoki Takaku, Sara A. Grimm, John D. Roberts, Kaliopi Chrysovergis, Brian D. Bennett, Page Myers, Lalith Perera, Charles J. Tucker, Charles M. Perou & Paul A. Wade

In breast cancer GATA3 is known to be frequently mutated, but the function of these mutations is unclear. Here, the authors utilise CRISPR-Cas9 to model frame-shift mutations in zinc finger 2 of GATA3, highlighting that GATA3 mutation can have gain- or loss-of function effects in breast cancer.

13 March 2018 | doi: 10.1038/s41467-018-03478-4
Breast cancer  Cancer epigenetics  Transcriptional regulatory elements 

Desmosomal cadherin association with Tctex-1 and cortactin-Arp2/3 drives perijunctional actin polymerization to promote keratinocyte delamination OPEN
Oxana Nekrasova, Robert M. Harmon, Joshua A. Broussard, Jennifer L. Koetsier, Lisa M. Godsel, Gillian N. Fitz, Margaret L. Gardel & Kathleen J. Green

The epidermis is a multi-layered epithelium formed by the differentiation of basal cells and movement into suprabasal layers. Here the authors define a role for the desmosomal cadherin desmoglein-1 in promoting the delamination of basal cells by remodeling the actin cytoskeleton through interactions with the dynein light chain Tctex-1 and cortactin.

13 March 2018 | doi: 10.1038/s41467-018-03414-6
Actin  Desmosomes  Dynein 

A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis OPEN
T. Azad, H. J. Janse van Rensburg, E. D. Lightbody, B. Neveu, A. Champagne, A. Ghaffari, V. R. Kay, Y. Hao, H. Shen, B. Yeung, B. A. Croy, K. L. Guan, F. Pouliot, J. Zhang, C. J. B. Nicol & X. Yang

The Hippo pathway is a major orchestrator of organ development and homeostasis. Here Azad and colleagues develop a biosensor to monitor the activity of the Hippo pathway component LATS and identify VEGF signalling as an upstream regulator of LATS, supporting a role for Hippo signalling during angiogenesis.

13 March 2018 | doi: 10.1038/s41467-018-03278-w
Angiogenesis  HIPPO signalling 

Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors OPEN
Julie George , Vonn Walter, Martin Peifer, Ludmil B. Alexandrov, Danila Seidel, Frauke Leenders, Lukas Maas, Christian Müller, Ilona Dahmen, Tiffany M. Delhomme, Maude Ardin, Noemie Leblay, Graham Byrnes, Ruping Sun, Aurélien De Reynies, Anne McLeer-Florin, Graziella Bosco, Florian Malchers, Roopika Menon, Janine Altmüller et al.

The molecular nature of large-cell neuroendocrine lung carcinomas (LCNEC) has remained unclear. Here, the authors show LCNECs represent a distinct transcriptional subgroup among lung cancers and comprise two molecular subgroups, type I (TP53 and STK11/KEAP1 alterations) and type II (TP53 and RB1 inactivation).

13 March 2018 | doi: 10.1038/s41467-018-03099-x
Cancer genomics  Small-cell lung cancer 

Structure-based design of chimeric antigens for multivalent protein vaccines OPEN
S. Hollingshead, I. Jongerius, R. M. Exley, S. Johnson, S. M. Lea & C. M. Tang

Factor H binding protein (fHbp) and PorA are components of experimental serogroup B N. meningitidis vaccines. Here the authors graft the VR2 loop of PorA onto an fHBp-based scaffold to demonstrate proof-of-principle of a chimeric antigen strategy and vaccination against meningococcal disease.

13 March 2018 | doi: 10.1038/s41467-018-03146-7
Meningitis  Protein vaccines 

Atrx inactivation drives disease-defining phenotypes in glioma cells of origin through global epigenomic remodeling OPEN
Carla Danussi, Promita Bose, Prasanna T. Parthasarathy, Pedro C. Silberman, John S. Van Arnam, Mark Vitucci, Oliver Y. Tang, Adriana Heguy, Yuxiang Wang, Timothy A. Chan, Gregory J. Riggins, Erik P. Sulman, Frederick Lang, Chad J. Creighton, Benjamin Deneen, C. Ryan Miller, David J. Picketts, Kasthuri Kannan & Jason T. Huse

ATRX inactivation frequently occurs in glioma. Here, the authors explore the role of ATRX inactivation in oncogenesis, highlighting ATRX deficiency driven epigenomic changes that influence the expression of genes crucial to the oncogenic phenotype.

13 March 2018 | doi: 10.1038/s41467-018-03476-6
Cancer genomics  CNS cancer  Differentiation  Epigenomics  RHO signalling 

Uniaxial strain control of spin-polarization in multicomponent nematic order of BaFe2As2 OPEN
T. Kissikov, R. Sarkar, M. Lawson, B. T. Bush, E. I. Timmons, M. A. Tanatar, R. Prozorov, S. L. Bud’ko, P. C. Canfield, R. M. Fernandes & N. J. Curro

A fundamental understanding of nematic order is one of the most important issues to explore in the high temperature superconductors. Here, the authors unveil an internal spin structure of the nematic order in BaFe2As2 by using nuclear magnetic resonance under precisely controlled tunable strain.

13 March 2018 | doi: 10.1038/s41467-018-03377-8
Magnetic properties and materials  Phase transitions and critical phenomena 

Warm Arctic episodes linked with increased frequency of extreme winter weather in the United States OPEN
Judah Cohen, Karl Pfeiffer & Jennifer A. Francis

Whether accelerated Arctic warming is favorable for more frequent severe winter weather remains controversial. Here the authors present an observational analysis that links Arctic warming to severe winter weather, showing that extreme weather is 2–4 times more likely in the eastern US when the Arctic is warm.

13 March 2018 | doi: 10.1038/s41467-018-02992-9
Atmospheric dynamics  Climate and Earth system modelling 

Role of monkeys in the sylvatic cycle of chikungunya virus in Senegal OPEN
Benjamin M. Althouse, Mathilde Guerbois, Derek A. T. Cummings, Ousmane M. Diop, Ousmane Faye, Abdourahmane Faye, Diawo Diallo, Bakary Djilocalisse Sadio, Abdourahmane Sow, Oumar Faye, Amadou A. Sall, Mawlouth Diallo, Brenda Benefit, Evan Simons, Douglas M. Watts, Scott C. Weaver & Kathryn A. Hanley

The authors examine the role of monkey populations in the sylvatic cycle of chikungunya virus in the Kédougou region, Senegal. The authors show that monkeys are amplification hosts, as opposed to reservoir hosts for infection. These findings expand our knowledge of the transmission dynamics of chikungunya virus in this region of Senegal.

13 March 2018 | doi: 10.1038/s41467-018-03332-7
Ecological epidemiology  Epidemiology  Viral infection  Virology 

Benchmarking common quantification strategies for large-scale phosphoproteomics OPEN
Alexander Hogrebe, Louise von Stechow, Dorte B. Bekker-Jensen, Brian T. Weinert, Christian D. Kelstrup & Jesper V. Olsen

Quantitative phosphoproteomics has become a standard method in molecular and cell biology. Here, the authors compare performance and parameters of phosphoproteome quantification by LFQ, SILAC, and MS2-/MS3-based TMT and introduce a TMT-adapted algorithm for calculating phosphorylation site stoichiometry.

13 March 2018 | doi: 10.1038/s41467-018-03309-6
DNA damage response  Mass spectrometry  Phosphorylation  Proteomics 

Integrated genomics and functional validation identifies malignant cell specific dependencies in triple negative breast cancer OPEN
Nirmesh Patel , Daniel Weekes, Konstantinos Drosopoulos, Patrycja Gazinska, Elodie Noel, Mamun Rashid, Hasan Mirza, Jelmar Quist, Fara Brasó-Maristany, Sumi Mathew, Riccardo Ferro, Ana Mendes Pereira, Cynthia Prince, Farzana Noor, Erika Francesch-Domenech, Rebecca Marlow, Emanuele de Rinaldis, Anita Grigoriadis, Spiros Linardopoulos, Pierfrancesco Marra et al.

Triple negative breast cancers harbor multiple copy number aberrations driving gene expression changes thought to underpin their malignant phenotypes. Here the authors integrate these features, finding and functionally validating 37 gene addictions among which they identify the mechanism of addiction to KIFC1, a potential selective drug target.

13 March 2018 | doi: 10.1038/s41467-018-03283-z
Breast cancer  Cancer genomics  Target identification  Target validation  Targeted therapies 

Molecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont OPEN
Benjamin Pluvinage, Julie M. Grondin, Carolyn Amundsen, Leeann Klassen, Paul E. Moote, Yao Xiao, Dallas Thomas, Nicholas A. Pudlo, Anuoluwapo Anele, Eric C. Martens, G. Douglas Inglis, Richard E. R. Uwiera, Alisdair B. Boraston & D. Wade Abbott

Polysaccharides are the primary structural cell wall and energy storage molecules of seaweed. Here, the authors show how the geographically restricted dietary polysaccharide agarose is selectively utilized by the human intestinal bacterium Bacteroides uniformis, providing insight into how carbohydrate metabolism evolves within the human microbiome.

13 March 2018 | doi: 10.1038/s41467-018-03366-x
Bacteria  Hydrolases  Microbial ecology  Polysaccharides 

Structural change as a key component for agricultural non-CO2 mitigation efforts OPEN
Stefan Frank, Robert Beach, Petr Havlík, Hugo Valin, Mario Herrero, Aline Mosnier, Tomoko Hasegawa, Jared Creason, Shaun Ragnauth & Michael Obersteiner

To achieve the climate target of the Paris Agreement substantial emission reductions will be required across economic sectors. Here the authors show that agriculture can make a significant contribution to non-CO2 mitigation efforts through structural change in the livestock sector and the deployment of technical options.

13 March 2018 | doi: 10.1038/s41467-018-03489-1
Agriculture  Carbon cycle  Climate-change mitigation 

Scalable WDM phase regeneration in a single phase-sensitive amplifier through optical time lenses OPEN
Pengyu Guan, Francesco Da Ros, Mads Lillieholm, Niels-Kristian Kjøller, Hao Hu, Kasper Meldgaard Røge, Michael Galili, Toshio Morioka & Leif Katsuo Oxenløwe

Scalable solutions for data regeneration of multiple parallel channels are elusive. Here the authors report a scalable wavelength-division multiplexing technique for phase regeneration and demonstrate the highest reported number of regenerated wavelength-division multiplexed channels in a single phase regenerator.

13 March 2018 | doi: 10.1038/s41467-018-03458-8
Fibre optics and optical communications  Nonlinear optics 

A meta-analysis of birth-origin effects on reproduction in diverse captive environments OPEN
Katherine A. Farquharson, Carolyn J. Hogg & Catherine E. Grueber

Aquaculture, conservation, and biological research are reliant on the successful breeding of animals in captivity. Here, Farquharson et al. report that, in captivity, captive-born animals have decreased reproductive success compared to wild-born individuals, across diverse species and contexts.

13 March 2018 | doi: 10.1038/s41467-018-03500-9
Evolution  Zoology 

Wing bone geometry reveals active flight in Archaeopteryx OPEN
Dennis F. A. E. Voeten, Jorge Cubo, Emmanuel de Margerie, Martin Röper, Vincent Beyrand, Stanislav Bureš, Paul Tafforeau & Sophie Sanchez

Archaeopteryx had a mix of traits seen in non-flying dinosaurs and flying birds, leading to debate on whether it had powered flight. Here, Voeten et al. compare wing bone architecture from Archaeopteryx and both flying and non-flying archosaurs, supporting that Archaeopteryx had powered flight but with a different stroke than that of modern birds.

13 March 2018 | doi: 10.1038/s41467-018-03296-8
Biomechanics  Palaeontology 

miR200-regulated CXCL12β promotes fibroblast heterogeneity and immunosuppression in ovarian cancers OPEN
Anne-Marie Givel, Yann Kieffer, Alix Scholer-Dahirel, Philemon Sirven, Melissa Cardon, Floriane Pelon, Ilaria Magagna, Géraldine Gentric, Ana Costa, Claire Bonneau, Virginie Mieulet, Anne Vincent-Salomon & Fatima Mechta-Grigoriou

Cancer-associated fibroblasts (CAFs) are an important part of the tumor microenvironment. Here the authors characterize four subsets of CAFs across human samples of ovarian cancer subtypes and show in the mesenchymal subtype a specific CAF-S1 population that attracts immunosuppressive Tregs via CXCL12β.

13 March 2018 | doi: 10.1038/s41467-018-03348-z
Cancer microenvironment  Ovarian cancer  Tumour heterogeneity 

Efficient molecular evolution to generate enantioselective enzymes using a dual-channel microfluidic droplet screening platform OPEN
Fuqiang Ma, Meng Ting Chung, Yuan Yao, Robert Nidetz, Lap Man Lee, Allen P. Liu, Yan Feng, Katsuo Kurabayashi & Guang-Yu Yang

Optimizing an enzyme usually requires testing thousands of variants, thus consuming large amounts of material and time. Here, the authors present a method that allows for measuring two different activities of the same enzyme simultaneously instead of doing two consecutive rounds of screening.

12 March 2018 | doi: 10.1038/s41467-018-03492-6
High-throughput screening  Hydrolases  Protein design 

A systematic approach to the development of a safe live attenuated Zika vaccine OPEN
Swee Sen Kwek, Satoru Watanabe, Kuan Rong Chan, Eugenia Z. Ong, Hwee Cheng Tan, Wy Ching Ng, Mien T. X. Nguyen, Esther S. Gan, Summer L. Zhang, Kitti W. K. Chan, Jun Hao Tan, October M. Sessions, Menchie Manuel, Julien Pompon, Camillus Chua, Sharifah Hazirah, Karl Tryggvason, Subhash G. Vasudevan & Eng Eong Ooi

A Zika virus (ZIKV) vaccine should provide long-lasting immunity, which may be achieved with a live-attenuated vaccine. Here, Kwek et al. select an interferon-restricted, attenuated ZIKV variant and evaluate replication and immunogenicity in mouse and mosquito models.

12 March 2018 | doi: 10.1038/s41467-018-03337-2
Live attenuated vaccines  Viral host response  Viral infection 

Disentangling the role of floral sensory stimuli in pollination networks OPEN
Aphrodite Kantsa, Robert A. Raguso, Adrian G. Dyer, Jens M. Olesen, Thomas Tscheulin & Theodora Petanidou

Can floral phenotype predict the most influential species for maintaining plant–pollinator communities? Here, Kantsa et al. develop a methodology for trait-based analysis, revealing the critical role of floral scent, and floral colour as perceived by insects, in shaping visitation networks.

12 March 2018 | doi: 10.1038/s41467-018-03448-w
Community ecology  Ecological networks  Plant ecology 

Vesicular glutamate release from central axons contributes to myelin damage OPEN
Sean Doyle, Daniel Bloch Hansen, Jasmine Vella, Peter Bond, Glenn Harper, Christian Zammit, Mario Valentino & Robert Fern

Neuronal activity can lead to vesicular release of glutamate. Here the authors demonstrate that vesicular release of glutamate occurs in axons during ischemic conditions, and that an allosteric modulator of GluN2C/D is protective in models of ischemic injury.

12 March 2018 | doi: 10.1038/s41467-018-03427-1
Myelin biology and repair  Stroke 

Development of the social brain from age three to twelve years OPEN
Hilary Richardson, Grace Lisandrelli, Alexa Riobueno-Naylor & Rebecca Saxe

Though adults’ brains process the internal states of others’ bodies versus others’ minds in distinct brain regions, it is not clear when this functional dissociation emerges. Here, authors study 3–12 year olds and show that these networks are distinct by age 3 and become even more distinct with age.

12 March 2018 | doi: 10.1038/s41467-018-03399-2
Agency  Cognitive neuroscience  Empathy  Psychology 

Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor OPEN
Felipe Rivas, Osama K. Zahid, Heidi L. Reesink, Bridgette T. Peal, Alan J. Nixon, Paul L. DeAngelis, Aleksander Skardal, Elaheh Rahbar & Adam R. Hall

Involved in various diseases, hyaluronic acid is an important indicator of pathophysiology. Here, the authors report on a solid-state nanopore for the detection of the molecular weight and abundance of hyaluronic acid and demonstrate the system by studying an equine model of osteoarthritis

12 March 2018 | doi: 10.1038/s41467-018-03439-x
Biosensors  Nanopores  Proteomics 

CoA synthase regulates mitotic fidelity via CBP-mediated acetylation OPEN
Chao-Chieh Lin, Mayumi Kitagawa, Xiaohu Tang, Ming-Hsin Hou, Jianli Wu, Dan Chen Qu, Vinayaka Srinivas, Xiaojing Liu, J. Will Thompson, Bernard Mathey-Prevot, Tso-Pang Yao, Sang Hyun Lee & Jen-Tsan Chi

The temporal activation of kinases and timely ubiquitin-mediated degradation is central to faithful mitosis. Here the authors show that acetylation controlled by Coenzyme A synthase (COASY) and acetyltransferase CBP constitutes a mechanism that ensures faithful mitosis.

12 March 2018 | doi: 10.1038/s41467-018-03422-6
Acetylation  Mitosis 

Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide OPEN
Kok Fei Chan, Benjamin S. Gully, Stephanie Gras, Dennis X. Beringer, Lars Kjer-Nielsen, Jonathan Cebon, James McCluskey, Weisan Chen & Jamie Rossjohn

Human leukocyte antigen (HLA) presents peptides to activate T cells, but many aspects in the T cell receptor (TCR)/HLA interaction remain unclear. Here the authors show, via structural data, that two TCRs differentially recognize the same tumour peptide/HLA complex and induce contrasting conformation changes of the peptide.

12 March 2018 | doi: 10.1038/s41467-018-03321-w
Adaptive immunity  Antigen processing and presentation  Tumour immunology  X-ray crystallography 

Inhibition of neuronal FLT3 receptor tyrosine kinase alleviates peripheral neuropathic pain in mice OPEN
Cyril Rivat , Chamroeun Sar, Ilana Mechaly, Jean-Philippe Leyris, Lucie Diouloufet, Corinne Sonrier, Yann Philipson, Olivier Lucas, Sylvie Mallié, Antoine Jouvenel, Adrien Tassou, Henri Haton, Stéphanie Venteo, Jean-Philippe Pin, Eric Trinquet, Fabienne Charrier-Savournin, Alexandre Mezghrani, Willy Joly, Julie Mion, Martine Schmitt et al.

Sensitisation of dorsal root ganglia neurons contributes to neuropathic pain. Here the authors demonstrate the cytokine FL contributes to sensitisation of DRGs via its receptor FLT3 expressed on neurons, and identify a novel FLT3 inhibitor that attenuates neuropathic pain in mice.

12 March 2018 | doi: 10.1038/s41467-018-03496-2
Chronic pain  Neuroimmunology 

Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein OPEN
Jovan Nikolic, Laura Belot, Hélène Raux, Pierre Legrand, Yves Gaudin & Aurélie A. Albertini

Glycoprotein G of vesicular stomatitis virus (VSV) enables viral entry by binding to the major VSV receptor LDL-R. Here the authors present crystal structures of G in complex with two distinct CR domains of LDL-R, identifying structural determinants for VSV infectivity in mammalian and insect cells.

12 March 2018 | doi: 10.1038/s41467-018-03432-4
Viral proteins  Virus–host interactions  X-ray crystallography 

TRiC controls transcription resumption after UV damage by regulating Cockayne syndrome protein A OPEN
Alex Pines, Madelon Dijk, Matthew Makowski, Elisabeth M. Meulenbroek, Mischa G. Vrouwe, Yana van der Weegen, Marijke Baltissen, Pim J. French, Martin E. van Royen, Martijn S. Luijsterburg, Leon H. Mullenders, Michiel Vermeulen, Wim Vermeulen, Navraj S. Pannu & Haico van Attikum

An integrated network of chaperones and protein degradation machineries called the proteostasis network (PN) is required to maintain protein homeostasis. Here the authors show that one of the components of the PN, the chaperonin TRiC, interacts with the core transcription-coupled nucleotide excision repair protein CSA to ensure its assembly into the CRLCSA complex.

12 March 2018 | doi: 10.1038/s41467-018-03484-6
Chaperones  Nucleotide excision repair 

Evidence for ephemeral middle Eocene to early Oligocene Greenland glacial ice and pan-Arctic sea ice OPEN
Aradhna Tripati & Dennis Darby

With rapidly disappearing ice, understanding the past behavior of the cryosphere is critical. Here, the authors indicate the initiation and disappearance of glaciation on Greenland and Arctic sea ice coincided in the past, synchronous with Antarctic ice and global ice volume, and a CO2 threshold of ~500 p.p.m.v.

12 March 2018 | doi: 10.1038/s41467-018-03180-5
Cryospheric science  Palaeoceanography  Palaeoclimate 

Capture Hi-C identifies putative target genes at 33 breast cancer risk loci OPEN
Joseph S. Baxter, Olivia C. Leavy, Nicola H. Dryden, Sarah Maguire, Nichola Johnson, Vita Fedele, Nikiana Simigdala, Lesley-Ann Martin, Simon Andrews, Steven W. Wingett, Ioannis Assiotis, Kerry Fenwick, Ritika Chauhan, Alistair G. Rust, Nick Orr, Frank Dudbridge, Syed Haider & Olivia Fletcher

Risk loci for breast cancer have been identified by genome-wide association studies. Here, the authors use Capture Hi-C to identify 110 putative target genes at 33 loci and assessed associations of gene expression, SNP genotype, and survival, providing evidence of mechanisms that may influence the prognosis and risk of breast cancer.

12 March 2018 | doi: 10.1038/s41467-018-03411-9
Breast cancer  Cancer genetics 

Large enhancement of response times of a protein conformational switch by computational design OPEN
Alex J. DeGrave, Jeung-Hoi Ha, Stewart N. Loh & Lillian T. Chong

The rational optimization of response times of protein conformational switches is a major challenge for biomolecular switch design. Here the authors present a generally applicable computational design strategy that in combination with biophysical experiments can improve response times using a Ca2+-sensor as an example.

09 March 2018 | doi: 10.1038/s41467-018-03228-6
Computational biophysics  Molecular biophysics 

Paracrine cellular senescence exacerbates biliary injury and impairs regeneration OPEN
Sofia Ferreira-Gonzalez, Wei-Yu Lu, Alexander Raven, Benjamin Dwyer, Tak Yung Man, Eoghan O’Duibhir, Philip J. Starkey Lewis, Lara Campana, Tim J. Kendall, Thomas G. Bird, Nuria Tarrats, Juan-Carlos Acosta, Luke Boulter & Stuart J. Forbes

Senescence has been suggested as causing biliary cholangiopathies but how this is regulated is unclear. Here, the authors generate a mouse model of biliary senescence by deleting Mdm2 in bile ducts and show that inhibiting TGFβ limits senescence-dependent aggravation of cholangiopathies.

09 March 2018 | doi: 10.1038/s41467-018-03299-5
Bile ducts  Liver fibrosis  Mechanisms of disease  Senescence 

Statistical ensembles without typicality OPEN
Paul Boes, Henrik Wilming, Jens Eisert & Rodrigo Gallego

The minimal amount of assumptions to justify the use of maximum-entropy ensembles is still debated. Here, the authors show that the transitions that a partially known system environment can undergo are the same allowed for the maximum entropy state which is compatible with the known information.

09 March 2018 | doi: 10.1038/s41467-018-03230-y
Information theory and computation  Quantum mechanics  Statistical physics, thermodynamics and nonlinear dynamics 

MRN complex-dependent recruitment of ubiquitylated BLM helicase to DSBs negatively regulates DNA repair pathways OPEN
Vivek Tripathi, Himanshi Agarwal, Swati Priya, Harish Batra, Priyanka Modi, Monica Pandey, Dhurjhoti Saha, Sathees C. Raghavan & Sagar Sengupta

Bloom helicase is recruited to double strand breaks in an ATM dependent manner. Here the authors show that Bloom helicase is recruited to double strand breaks in an ATM and MRN dependent manner with HR and NHEJ regulated by the helicase depending on the phase of the cell cycle.

09 March 2018 | doi: 10.1038/s41467-018-03393-8
DNA recombination  Double-strand DNA breaks  Homologous recombination  Non-homologous-end joining 

p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage OPEN
Marina E. Borisova, Andrea Voigt, Maxim A. X. Tollenaere, Sanjeeb Kumar Sahu, Thomas Juretschke, Nastasja Kreim, Niels Mailand, Chunaram Choudhary, Simon Bekker-Jensen, Masato Akutsu, Sebastian A. Wagner & Petra Beli

UV-light-induced DNA damage affects RNA metabolism but the underlying signalling pathways are largely unexplored. Here, the authors show that UV light triggers p38-MK2-mediated phosphorylation of the NELF complex, promoting its release from chromatin and concurrent transcriptional elongation.

09 March 2018 | doi: 10.1038/s41467-018-03417-3
DNA damage response  Phosphorylation  Proteomics  RNA metabolism 

Brain and eyes of Kerygmachela reveal protocerebral ancestry of the panarthropod head OPEN
Tae-Yoon S. Park, Ji-Hoon Kihm, Jusun Woo, Changkun Park, Won Young Lee, M. Paul Smith, David A. T. Harper, Fletcher Young, Arne T. Nielsen & Jakob Vinther

The arthropod head is complex and its evolution has been difficult to reconstruct. Here, Park et al. describe new specimens of the Cambrian stem-group euarthropod Kerygmachela that preserve evidence of primitive compound eyes and a unipartite brain, providing insight into the structure of the early arthropod head.

09 March 2018 | doi: 10.1038/s41467-018-03464-w
Evolutionary developmental biology  Palaeontology 

Risk of nontyphoidal Salmonella bacteraemia in African children is modified by STAT4 OPEN
James J. Gilchrist , Anna Rautanen, Benjamin P. Fairfax, Tara C. Mills, Vivek Naranbhai, Holly Trochet, Matti Pirinen, Esther Muthumbi, Salim Mwarumba, Patricia Njuguna, Neema Mturi, Chisomo L. Msefula, Esther N. Gondwe, Jenny M. MacLennan, Stephen J. Chapman, Malcolm E. Molyneux, Julian C. Knight, Chris C. A. Spencer, Thomas N. Williams, Calman A. MacLennan et al.

Nontyphoidal Salmonella (NTS) is a major cause of bacteraemia in children and HIV-infected adults in Africa. Here, Gilchrist et al. conduct a genome-wide association study and show that genetic variation in STAT4 is a determinant of NTS in Kenyan and Malawian children.

09 March 2018 | doi: 10.1038/s41467-017-02398-z
Bacterial infection  Genome-wide association studies 

Stabilizing spin spirals and isolated skyrmions at low magnetic field exploiting vanishing magnetic anisotropy OPEN
Marie Hervé, Bertrand Dupé, Rafael Lopes, Marie Böttcher, Maximiliano D. Martins, Timofey Balashov, Lukas Gerhard, Jairo Sinova & Wulf Wulfhekel

Skyrmions are promising for spintronics but usually require large spin-orbit coupling of 5d-metals and external magnetic field. Here the authors realize stabilization of isolated skyrmions at a 4d-metal interface of weak chiral interaction and magnetic anisotropy down to vanishing field.

09 March 2018 | doi: 10.1038/s41467-018-03240-w
Ferromagnetism  Spintronics  Surfaces, interfaces and thin films 

MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state OPEN
Vittoria Poli, Luca Fagnocchi, Alessandra Fasciani, Alessandro Cherubini, Stefania Mazzoleni, Sara Ferrillo, Annarita Miluzio, Gabriella Gaudioso, Valentina Vaira, Alice Turdo, Miriam Giaggianesi, Aurora Chinnici, Elisa Lipari, Silvio Bicciato, Silvano Bosari, Matilde Todaro & Alessio Zippo

Breast cancer tumors originating from mammary luminal epithelial cells are highly heterogeneous. Here, the authors show MYC-driven tumor initiation is reliant on cell reprogramming via an epigenetic program which leads to mammary luminal epithelial cells acquiring basal/stem cell-like properties.

09 March 2018 | doi: 10.1038/s41467-018-03264-2
Breast cancer  Histone post-translational modifications  Reprogramming  Transcriptional regulatory elements 

Ultrafast nonlinear optical response of Dirac fermions in graphene OPEN
Matthias Baudisch, Andrea Marini, Joel D. Cox, Tony Zhu, Francisco Silva, Stephan Teichmann, Mathieu Massicotte, Frank Koppens, Leonid S. Levitov, F. Javier García de Abajo & Jens Biegert

Graphene possesses a nonlinear optical response arising from its electronic dispersion. Here, the authors measure the response of graphene to an ultrafast optical field and provide an explanation of the quantum dynamics of Dirac carriers mediating the material’s nonlinear response.

09 March 2018 | doi: 10.1038/s41467-018-03413-7
Nonlinear optics  Optical properties and devices 

CDK6 inhibits white to beige fat transition by suppressing RUNX1 OPEN
Xiaoli Hou, Yongzhao Zhang, Wei Li, Alexander J. Hu, Chi Luo, Wenhui Zhou, Jamie K. Hu, Stefano G. Daniele, Jinfeng Wang, Jinghao Sheng, Yongsheng Fan, Andrew S. Greenberg, Stephen R. Farmer & Miaofen G. Hu

Beige adipocytes can arise from transdifferentiation of mature white adipocytes. Here the authors identify CDK6 as a key molecule involved in the white-to-beige adipocyte transdifferentiation and, therefore, as a regulator of organismal energy homeostasis in mice.

09 March 2018 | doi: 10.1038/s41467-018-03451-1
Mechanisms of disease  Metabolic disorders  Obesity 

Insc:LGN tetramers promote asymmetric divisions of mammary stem cells OPEN
Simone Culurgioni, Sara Mari, Paola Bonetti, Sara Gallini, Greta Bonetto, Martha Brennich, Adam Round, Francesco Nicassio & Marina Mapelli

During asymmetric divisions fate determinants and niche contacts segregate unequally between daughter cells, but the mechanism is unclear. Here the authors show that Insc:LGN tetramers promote assembly of Par3-Insc-LGN-GαiGDP complexes and asymmetric fate specification independently of microtubule motors.

09 March 2018 | doi: 10.1038/s41467-018-03343-4
Cell division  Structural biology 

p63 is a key regulator of iRHOM2 signalling in the keratinocyte stress response OPEN
Paola Arcidiacono, Catherine M. Webb, Matthew A. Brooke, Huiqing Zhou, Paul J. Delaney, Keat-Eng Ng, Diana C. Blaydon, Andrew Tinker, David P. Kelsell & Anissa Chikh

Mutations in the gene encoding iRHOM2 are associated with hyperproliferative epidermal disorders. Here, the authors show that iRHOM2 is a target gene of p63, that together they regulate inflammation, cell survival and response to oxidative stress, and inhibition of p63-iRHOM2 signalling with an antioxidant reduces epidermal inflammation.

09 March 2018 | doi: 10.1038/s41467-018-03470-y
Cell proliferation  Intermediate filaments  Skin diseases 

Sedimentary noise and sea levels linked to land–ocean water exchange and obliquity forcing OPEN
Mingsong Li, Linda A. Hinnov, Chunju Huang & James G. Ogg

The origin of large, long-term sea-level oscillations during non-glacial times remains uncertain. Here, the authors develop geological evidence that reveals astronomically forced land–ocean water exchange as a potential missing link for reconciling geological records and models of sea-level change.

08 March 2018 | doi: 10.1038/s41467-018-03454-y
Palaeoceanography  Palaeoclimate 

HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns OPEN
Vaibhav P. Pai, Alexis Pietak, Valerie Willocq, Bin Ye, Nian-Qing Shi & Michael Levin

The authors have previously shown that membrane voltage can influence embryonic patterning during development. Here, the authors computationally model how nicotine disrupts Xenopus embryogenesis by perturbing voltage gradients, and rescue nicotine-inducted defects with HCN2 channel expression.

08 March 2018 | doi: 10.1038/s41467-018-03334-5
Brain  Ion channels  Regeneration  Regeneration and repair in the nervous system 

Aberrant GlyRS-HDAC6 interaction linked to axonal transport deficits in Charcot-Marie-Tooth neuropathy OPEN
Zhongying Mo, Xiaobei Zhao, Huaqing Liu, Qinghua Hu, Xu-Qiao Chen, Jessica Pham, Na Wei, Ze Liu, Jiadong Zhou, Robert W. Burgess, Samuel L. Pfaff, C. Thomas Caskey, Chengbiao Wu, Ge Bai & Xiang-Lei Yang

Mutations in glycyl-tRNA synthetase (GlyRS) cause Charcot-Marie-Tooth disease, a neuromuscular disorder characterized by axonal degeneration. Here the authors show that mutant GlyRS interacts with histone deacetylase 6, resulting in increased deacetylation of α-tubulin and axonal transport deficits.

08 March 2018 | doi: 10.1038/s41467-018-03461-z
Acetylation  Molecular neuroscience  Neurodegeneration 

Design and validation of a foldable and photovoltaic wide-field epiretinal prosthesis OPEN
Laura Ferlauto, Marta Jole Ildelfonsa Airaghi Leccardi, Naïg Aurelia Ludmilla Chenais, Samuel Charles Antoine Gilliéron, Paola Vagni, Michele Bevilacqua, Thomas J. Wolfensberger, Kevin Sivula & Diego Ghezzi

Retinal prostheses are being developed to fight severe retinal diseases where wider visual field and higher visual acuity are desired. Here Ferlauto et al. design a foldable and wide-field epiretinal prosthesis that can meet the performance and safety requirements and show a long lifetime of 2 years.

08 March 2018 | doi: 10.1038/s41467-018-03386-7
Biomedical engineering  Polymers  Retina 

Activation of serotonin neurons promotes active persistence in a probabilistic foraging task OPEN
Eran Lottem, Dhruba Banerjee, Pietro Vertechi, Dario Sarra, Matthijs oude Lohuis & Zachary F. Mainen

Serotonin (5-HT) has been suggested to promote waiting through behavioral inhibition. Here, the authors use an active foraging task and optogenetic activation of 5-HT neurons to show that rather than passivity, these neurons enhance persistence in the face of delay.

08 March 2018 | doi: 10.1038/s41467-018-03438-y
Motivation  Reward 

An accurate and robust imputation method scImpute for single-cell RNA-seq data OPEN
Wei Vivian Li & Jingyi Jessica Li

Despite being widely performed in exploring cell heterogeneity and gene expression stochasticity, single cell RNA-seq analysis is complicated by excess zero counts (dropouts). Here, Li and Li develop scImpute for statistical imputation of dropouts in scRNA-seq data.

08 March 2018 | doi: 10.1038/s41467-018-03405-7
Statistical methods 

Nanoscale kinetics of asymmetrical corrosion in core-shell nanoparticles OPEN
Hao Shan, Wenpei Gao, Yalin Xiong, Fenglei Shi, Yucong Yan, Yanling Ma, Wen Shang, Peng Tao, Chengyi Song, Tao Deng, Hui Zhang, Deren Yang, Xiaoqing Pan & Jianbo Wu

Understanding how catalysts corrode during use is crucial in developing new, durable devices. Here, the authors studied the real-time corrosion of core-shell palladium-platinum nanocubes by electron microscopy and found two competitive etching mechanisms to dominate catalyst degradation behavior.

08 March 2018 | doi: 10.1038/s41467-018-03372-z
Corrosion  Electrocatalysis  Fuel cells  Nanoparticles 

Phosphorylation of conserved phosphoinositide binding pocket regulates sorting nexin membrane targeting OPEN
Marc Lenoir, Cansel Ustunel, Sandya Rajesh, Jaswant Kaur, Dimitri Moreau, Jean Gruenberg & Michael Overduin

Sorting nexin 3 (SNX3) is a phosphatidylinositol 3-phosphate binding protein that localizes to early endosomes. Here the authors use NMR to resolve SNX3′s membrane interactions, revealing that membrane binding is regulated through phosphorylation of a conserved serine by its lipid recognition site.

08 March 2018 | doi: 10.1038/s41467-018-03370-1
Endosomes  Solution-state NMR 

Strong phenotypic plasticity limits potential for evolutionary responses to climate change OPEN
Vicencio Oostra, Marjo Saastamoinen, Bas J. Zwaan & Christopher W. Wheat

Phenotypic plasticity—the ability to express multiple phenotypes from the same genome—is a widespread adaptation to environmental variability. Here, Oostra et al analyze transcriptomes of an African butterfly with distinct seasonal phenotypes, and observe lack of variation for plasticity, limiting potential for evolutionary responses to climate change.

08 March 2018 | doi: 10.1038/s41467-018-03384-9
Environmental health  Evolutionary ecology  Evolutionary genetics  Phenology  Transcriptomics 

Expansion of functional personalized cells with specific transgene combinations OPEN
Christoph Lipps , Franziska Klein, Tom Wahlicht, Virginia Seiffert, Milada Butueva, Jeannette Zauers, Theresa Truschel, Martin Luckner, Mario Köster, Roderick MacLeod, Jörn Pezoldt, Jochen Hühn, Qinggong Yuan, Peter Paul Müller, Henning Kempf, Robert Zweigerdt, Oliver Dittrich-Breiholz, Thomas Pufe, Rainer Beckmann, Wolf Drescher et al.

Personalised medicine requires cell cultures from defined genetic backgrounds, but providing sufficient numbers of cells is a challenge. Here the authors develop gene cocktails to expand primary cells from a variety of different tissues and species, and show that expanded endothelial and hepatic cells retain properties of the differentiated phenotype.

08 March 2018 | doi: 10.1038/s41467-018-03408-4
Cell culture  Cell therapies  Regenerative medicine 

The H2B deubiquitinase Usp22 promotes antibody class switch recombination by facilitating non-homologous end joining OPEN
Conglei Li, Thergiory Irrazabal, Clare C. So, Maribel Berru, Likun Du, Evelyn Lam, Alexanda K. Ling, Jennifer L. Gommerman, Qiang Pan-Hammarström & Alberto Martin

Class switch recombination (CSR) requires break and repair of immunoglobulin DNA. Here the authors show that the histone deubiquitinase Usp22 is involved in V(D)J recombination and CSR of IgG and IgE, but not IgA, and that IgG CSR is dependent on the canonical c-NHEJ pathway, whereas IgA CSR is more dependent on the alternative A-EJ pathway.

08 March 2018 | doi: 10.1038/s41467-018-03455-x
B-cell receptor  Class switch recombination 

An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm OPEN
Christian L. Lino Cardenas, Chase W. Kessinger, Yisha Cheng, Carolyn MacDonald, Thomas MacGillivray, Brian Ghoshhajra, Luai Huleihel, Saifar Nuri, Ashish S. Yeri, Farouc A. Jaffer, Naftali Kaminski, Patrick Ellinor, Neal L. Weintraub, Rajeev Malhotra, Eric M. Isselbacher & Mark E. Lindsay

Vascular smooth muscle cell (VSMC) dysfunction is a common feature of thoracic aortic aneurysms (TAAs). Here, Lino Cardenas and colleagues show that the formation of a HDAC9-MALAT1-BRG1 complex promotes VSMC dysfunction in TAA by epigenetically altering the expression of key components of the cytoskeleton in VSMCs.

08 March 2018 | doi: 10.1038/s41467-018-03394-7
Actin  Aneurysm  Long non-coding RNAs 

Surface plasmon resonance extension through two-block metal-conducting polymer nanorods OPEN
Insub Jung, Minkyung Kim, Min Kwak, Geonwoo Kim, Minsun Jang, Sang Min Kim, Doo Jae Park & Sungho Park

Localized surface plasmon resonance can be exploited for a range of applications, but remains difficult to tailor in metal-organic nanostructures. Here the authors synthesize gold-polypyrrole nanorods and observe a unique extended surface plasmon resonance, which they find to be tunable through doping.

08 March 2018 | doi: 10.1038/s41467-018-03453-z
Materials chemistry  Nanophotonics and plasmonics  Nanoscale materials 

Oscillating modes of driven colloids in overdamped systems OPEN
Johannes Berner, Boris Müller, Juan Ruben Gomez-Solano, Matthias Krüger & Clemens Bechinger

The motion of microparticles suspended in liquids is assumed to be dominated by viscous forces. Here, Berner et al. challenge this consensus by observing underdamped particle oscillations in a viscoelastic fluid and attributing it to the non-equilibrium fluctuations of liquid excited by particles.

08 March 2018 | doi: 10.1038/s41467-018-03345-2
Fluid dynamics  Thermodynamics 

Transient rheology of the Sumatran mantle wedge revealed by a decade of great earthquakes OPEN
Qiang Qiu, James D. P. Moore, Sylvain Barbot, Lujia Feng & Emma M. Hill

The rheology of the upper mantle is key to understanding how plate tectonics may evolve. Here, using GPS and tide-gauge measurements along the Sumatran subduction zone, the authors’ show that a bi-viscous rheology model is needed to explain the stress and strain evolution of the upper mantle following earthquakes.

08 March 2018 | doi: 10.1038/s41467-018-03298-6
Geophysics  Tectonics 

A proteomic landscape of diffuse-type gastric cancer OPEN
Sai Ge , Xia Xia, Chen Ding, Bei Zhen, Quan Zhou, Jinwen Feng, Jiajia Yuan, Rui Chen, Yumei Li, Zhongqi Ge, Jiafu Ji, Lianhai Zhang, Jiayuan Wang, Zhongwu Li, Yumei Lai, Ying Hu, Yanyan Li, Yilin Li, Jing Gao, Lin Chen et al.

Diffuse-type gastric cancer (DGC) accounts for 30% of gastric cancers and has few treatment options. Here the authors present a mutation and proteome dataset for 84 patients, identifying three major classes of DGC and indicating potential targets for therapy.

08 March 2018 | doi: 10.1038/s41467-018-03121-2
Gastric cancer  Proteomics 

Turning microplastics into nanoplastics through digestive fragmentation by Antarctic krill OPEN
Amanda L. Dawson, So Kawaguchi, Catherine K. King, Kathy A. Townsend, Robert King, Wilhelmina M. Huston & Susan M. Bengtson Nash

Microplastics are emerging ocean contaminants, but their fates in the ocean environment are poorly understood. Here the authors show that Antarctic krill digest micro plastics into nano plastics, thereby generating particles of a size that can cross biological and physical barriers.

08 March 2018 | doi: 10.1038/s41467-018-03465-9
Ecology  Environmental impact  Marine biology 

Cation vacancy stabilization of single-atomic-site Pt1/Ni(OH)x catalyst for diboration of alkynes and alkenes OPEN
Jian Zhang, Xi Wu, Weng-Chon Cheong, Wenxing Chen, Rui Lin, Jia Li, Lirong Zheng, Wensheng Yan, Lin Gu, Chen Chen, Qing Peng, Dingsheng Wang & Yadong Li

Development of single-atomic-site catalysts with high metal loading remains a challenge. Here, the authors report a nickel hydroxide nanoboard with abundant Ni2+ vacancy defects serving as the support to achieve high platinum loading by simple wet impregnation.

08 March 2018 | doi: 10.1038/s41467-018-03380-z
Heterogeneous catalysis  Materials chemistry  Materials for energy and catalysis 

The oxidized phospholipid oxPAPC protects from septic shock by targeting the non-canonical inflammasome in macrophages OPEN
Lan H. Chu, Mohanalaxmi Indramohan, Rojo A. Ratsimandresy, Anu Gangopadhyay, Emily P. Morris, Denise M. Monack, Andrea Dorfleutner & Christian Stehlik

Non-canonical inflammasome activation is mediated by caspase-11 in mice and caspase-4 in humans. Here the authors show that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) competes with LPS for binding to these caspases and in so doing is a negative regulator of non-canonical inflammasome activation in macrophages, but not in dendritic cells.

08 March 2018 | doi: 10.1038/s41467-018-03409-3
Inflammasome  Pattern recognition receptors 

Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole OPEN
Yusuke Minato, Surendra Dawadi, Shannon L. Kordus, Abiram Sivanandam, Courtney C. Aldrich & Anthony D. Baughn

The antibiotics trimethoprim (TMP) and sulfamethoxazole (SMX) synergistically inhibit bacterial tetrahydrofolate biosynthesis, apparently because SMX potentiates TMP activity. Here, Minato et al. identify a metabolic feedback loop in this pathway, revealing that TMP also potentiates SMX activity.

08 March 2018 | doi: 10.1038/s41467-018-03447-x
Antibiotics  Bacteria  Bacteriology  Metabolic pathways 
  Latest Addendum    
Addendum: Application of bio-orthogonal proteome labeling to cell transplantation and heterochronic parabiosis OPEN
Yan Liu, Michael J. Conboy, Melod Mehdipour, Yutong Liu, Thanhtra P. Tran, Aaron Blotnick, Prasanna Rajan, Thalie Cavalcante Santos & Irina M. Conboy
13 March 2018 | doi: 10.1038/s41467-017-02779-4
Ageing  Proteome  Transgenic organisms 
  Latest Author Corrections    
Author Correction: Liquid crystal elastomer coatings with programmed response of surface profile OPEN
Greta Babakhanova, Taras Turiv, Yubing Guo, Matthew Hendrikx, Qi-Huo Wei, Albert P. H. J. Schenning, Dirk J. Broer & Oleg D. Lavrentovich
14 March 2018 | doi: 10.1038/s41467-018-03634-w
Liquid crystals  Polymers 

Author Correction: Super-achromatic monolithic microprobe for ultrahigh-resolution endoscopic optical coherence tomography at 800 nm OPEN
Wu Yuan, Robert Brown, Wayne Mitzner, Lonny Yarmus & Xingde Li
14 March 2018 | doi: 10.1038/s41467-018-03637-7
Biomedical engineering  Biophotonics  Endoscopy 

Author Correction: Nuclear lamin A/C harnesses the perinuclear apical actin cables to protect nuclear morphology OPEN
Jeong-Ki Kim, Arghavan Louhghalam, Geonhui Lee, Benjamin W. Schafer, Denis Wirtz & Dong-Hwee Kim
13 March 2018 | doi: 10.1038/s41467-018-03450-2
Nuclear envelope  Nucleoskeleton  Stress fibres 

Author Correction: Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor OPEN
Michael H. Berry, Amy Holt, Joshua Levitz, Johannes Broichhagen, Benjamin M. Gaub, Meike Visel, Cherise Stanley, Krishan Aghi, Yang Joon Kim, Kevin Cao, Richard H Kramer, Dirk Trauner, John Flannery & Ehud Y. Isacoff
13 March 2018 | doi: 10.1038/s41467-018-03585-2
Molecular neuroscience  Protein design  Retina 

Author Correction: Protein-peptide association kinetics beyond the seconds timescale from atomistic simulations OPEN
Fabian Paul, Christoph Wehmeyer, Esam T. Abualrous, Hao Wu, Michael D. Crabtree, Johannes Schöneberg, Jane Clarke, Christian Freund, Thomas R. Weikl & Frank Noé
09 March 2018 | doi: 10.1038/s41467-018-03452-0
Biological physics  Chemical physics  Computational biophysics  Reaction kinetics and dynamics 

Author Correction: Energy use and life cycle greenhouse gas emissions of drones for commercial package delivery OPEN
Joshuah K. Stolaroff, Constantine Samaras, Emma R. O’Neill, Alia Lubers, Alexandra S. Mitchell & Daniel Ceperley
08 March 2018 | doi: 10.1038/s41467-018-03457-9
Climate-change mitigation  Energy efficiency  Energy science and technology 
  Latest Publisher Corrections    
Publisher Correction: Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells OPEN
Luiz Carlos Caires-Júnior , Ernesto Goulart, Uirá Souto Melo, Bruno Henrique Silva Araujo, Lucas Alvizi, Alessandra Soares-Schanoski, Danyllo Felipe de Oliveira, Gerson Shigeru Kobayashi, Karina Griesi-Oliveira, Camila Manso Musso, Murilo Sena Amaral, Lucas Ferreira daSilva, Renato Mancini Astray, Sandra Fernanda Suárez-Patiño, Daniella Cristina Ventini, Sérgio Gomes da Silva, Guilherme Lopes Yamamoto, Suzana Ezquina, Michel Satya Naslavsky, Kayque Alves Telles-Silva et al.
13 March 2018 | doi: 10.1038/s41467-018-03497-1
Neural stem cells  Viral host response 

Publisher Correction: Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid OPEN
Youngzee Song, Huihao Zhou, My-Nuong Vo, Yi Shi, Mir Hussain Nawaz, Oscar Vargas-Rodriguez, Jolene K. Diedrich, John R. Yates III, Shuji Kishi, Karin Musier-Forsyth & Paul Schimmel
13 March 2018 | doi: 10.1038/s41467-018-03594-1
Enzyme mechanisms  Proteins  tRNAs  X-ray crystallography 

Publisher Correction: Statistical modeling of RNA structure profiling experiments enables parsimonious reconstruction of structure landscapes OPEN
Hua Li & Sharon Aviran
13 March 2018 | doi: 10.1038/s41467-018-03519-y
Computational science  Statistical methods 

Publisher Correction: Mammalian display screening of diverse cystine-dense peptides for difficult to drug targets OPEN
Zachary R. Crook, Gregory P. Sevilla, Della Friend, Mi-Youn Brusniak, Ashok D. Bandaranayake, Midori Clarke, Mesfin Gewe, Andrew J. Mhyre, David Baker, Roland K. Strong, Philip Bradley & James M. Olson
09 March 2018 | doi: 10.1038/s41467-018-03350-5
Drug development  High-throughput screening  Protein design  Recombinant peptide therapy 

Publisher Correction: Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer’s disease OPEN
Aman P. Mann, Pablo Scodeller, Sazid Hussain, Gary B. Braun, Tarmo Mölder, Kadri Toome, Rajesh Ambasudhan, Tambet Teesalu, Stuart A. Lipton & Erkki Ruoslahti
09 March 2018 | doi: 10.1038/s41467-018-03517-0
Alzheimer's disease  Neuro–vascular interactions 

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