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Nature Communications - 24 October 2018

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Frontiers in Regenerative Medicine: 2019 Innovators in Science Award Symposium

April 26, 2019 - Kanagawa, Japan

This free symposium, featuring keynote speaker Shinya Yamanaka, will honor the 2019 Innovators in Science Award Winners and highlight discoveries by distinguished scientists who are advancing therapeutic applications of regenerative medicine.

  Latest Review View all Articles  

Metallo-polyelectrolytes as a class of ionic macromolecules for functional materials OPEN
Tianyu Zhu, Ye Sha, Jing Yan, Parasmani Pageni, Md Anisur Rahman, Yi Yan & Chuanbing Tang

Polyelectrolytes are a class of macromolecules containing charged groups. Here the authors review properties and functions of metallo-polyelectrolytes to shed light on how to harness fundamental physiochemical properties for applications in biomedical sciences and advanced materials.

18 October 2018 | doi: 10.1038/s41467-018-06475-9
Polymer characterization  Polymer synthesis  Polymers 
  Latest Articles View all Articles  

Structural insights into cGAMP degradation by Ecto-nucleotide pyrophosphatase phosphodiesterase 1 OPEN
Kazuki Kato, Hiroshi Nishimasu, Daisuke Oikawa, Seiichi Hirano, Hisato Hirano, Go Kasuya, Ryuichiro Ishitani, Fuminori Tokunaga & Osamu Nureki

Ecto-nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein that hydrolyzes both ATP and cGAMP. Here the authors present the crystal structures of the extracellular domain of mouse ENPP1 in complex with 3′3′-cGAMP and the reaction intermediate pA(3′,5′)pG and discuss mechanistic implications.

24 October 2018 | doi: 10.1038/s41467-018-06922-7
Enzyme mechanisms  Molecular biology  X-ray crystallography 

Slc7a5 regulates Kv1.2 channels and modifies functional outcomes of epilepsy-linked channel mutations OPEN
Victoria A. Baronas, Runying Y. Yang, Luis Carlos Morales, Simonetta Sipione & Harley T. Kurata

Kv1.2 is a voltage-gated potassium channel that influences action potential generation and propagation in the central nervous system. Here authors use electrophysiology and find that Slc7a5, a neutral amino acid transporter, has a profound impact on Kv1.2.

24 October 2018 | doi: 10.1038/s41467-018-06859-x
Ion channels in the nervous system  Mechanisms of disease  Neurodevelopmental disorders  Protein–protein interaction networks 

The signalling conformation of the insulin receptor ectodomain OPEN
Felix Weis, John G. Menting, Mai B. Margetts, Shu Jin Chan, Yibin Xu, Norbert Tennagels, Paulus Wohlfart, Thomas Langer, Christoph W. Müller, Matthias K. Dreyer & Michael C. Lawrence

The insulin receptor plays a key role in many physiological processes, yet how insulin effects receptor signaling at the structural level remains incomplete. Here the authors present a high-resolution cryo-EM structure of a high-affinity form of the insulin-bound insulin receptor ectodomain that sheds light on the mechanism of signal transduction.

24 October 2018 | doi: 10.1038/s41467-018-06826-6
Cryoelectron microscopy  Diabetes  Insulin signalling 

Expression-based drug screening of neural progenitor cells from individuals with schizophrenia OPEN
Benjamin Readhead, Brigham J. Hartley, Brian J. Eastwood, David A. Collier, David Evans, Richard Farias, Ching He, Gabriel Hoffman, Pamela Sklar, Joel T. Dudley, Eric E. Schadt, Radoslav Savić & Kristen J. Brennand

Unbiased large scale screening of small molecules for drug discovery in psychiatric disease is technically challenging and financially costly. Here, Readhead and colleagues integrate in silico and in vitro approaches to design and conduct transcriptomic drug screening in schizophrenia patient-derived neural cells, in order to survey novel pathologies and points of intervention.

24 October 2018 | doi: 10.1038/s41467-018-06515-4
Data integration  High-throughput screening  Induced pluripotent stem cells 

Gene synthesis allows biologists to source genes from farther away in the tree of life OPEN
Aditya M. Kunjapur, Philipp Pfingstag & Neil C. Thompson

Gene synthesis has expanded the ability to modify and create DNA sequences, with implications for biosurveillance. The authors use machine learning and codon theory to identify synthetic genes in Addgene data, and show that synthesis accelerates human-directed gene transfer across the tree of life.

24 October 2018 | doi: 10.1038/s41467-018-06798-7
Machine learning  Phylogenomics  Synthetic biology 

Sleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients OPEN
M. Rosanova, M. Fecchio, S. Casarotto, S. Sarasso, A. G. Casali, A. Pigorini, A. Comanducci, F. Seregni, G. Devalle, G. Citerio, O. Bodart, M. Boly, O. Gosseries, S. Laureys & M. Massimini

Many brain-injured patients retain large cortical islands that are intact, active and reactive but blocked in a state of low complexity, leading to unconsciousness. Here, the authors show that this loss of complexity is due to the pathological engagement of sleep-like neuronal mechanisms.

24 October 2018 | doi: 10.1038/s41467-018-06871-1
Brain injuries  Excitability  Neuroscience  Sleep 

SOX17 regulates uterine epithelial–stromal cross-talk acting via a distal enhancer upstream of Ihh OPEN
Xiaoqiu Wang, Xilong Li, Tianyuan Wang, San-Pin Wu, Jae-Wook Jeong, Tae Hoon Kim, Steven L. Young, Bruce A. Lessey, Rainer B. Lanz, John P. Lydon & Francesco J. DeMayo

The transcription factor SOX17 is important for uterine gland formation, fertility, and embryo implantation in mouse. Here the authors show that SOX17 is upstream of Indian hedgehog to regulate mouse uterine receptivity, and their analysis of uterine tissue from endometriosis patients suggests the same function in humans.

24 October 2018 | doi: 10.1038/s41467-018-06652-w
Embryology  Intrauterine growth  Reproductive disorders 

Multi-hierarchical profiling the structure-activity relationships of engineered nanomaterials at nano-bio interfaces OPEN
Xiaoming Cai, Jun Dong, Jing Liu, Huizhen Zheng, Chitrada Kaweeteerawat, Fangjun Wang, Zhaoxia Ji & Ruibin Li

Understanding nano-bio interactions is key to optimizing the biocompatible design of nanomaterials. Here, the authors combine proteomic and metabolomics studies to evaluate the effect of varying physicochemical properties of iron oxide nanoparticles in macrophage-like cells and mouse lungs.

24 October 2018 | doi: 10.1038/s41467-018-06869-9
Inflammation  Metabolomics  Nanotoxicology  Proteomics 

Shear-band affected zone revealed by magnetic domains in a ferromagnetic metallic glass OPEN
L. Q. Shen, P. Luo, Y. C. Hu, H. Y. Bai, Y. H. Sun, B. A. Sun, Y. H. Liu & W. H. Wang

Metallic glasses deform along nanoscale shear bands, and while it is known that they affect the neighboring glass regions, exactly how is unclear. Here, the authors use magnetic force microscopy to atomically resolve the shear-band affected zone and show its effects extends much further than previously thought.

24 October 2018 | doi: 10.1038/s41467-018-06919-2
Glasses  Mechanical properties  Metals and alloys 

Measuring macromolecular size distributions and interactions at high concentrations by sedimentation velocity OPEN
Sumit K. Chaturvedi, Jia Ma, Patrick H. Brown, Huaying Zhao & P. Schuck

Many aspects of concentrated macromolecular solutions, such as encountered in cytosol or in pharmaceutical formulations, are dependent on particle size distributions and weak intermolecular interactions. Here, the authors exploit hydrodynamic separation in the centrifugal field to measure both.

24 October 2018 | doi: 10.1038/s41467-018-06902-x
Biological physics  Biological techniques  Chemical engineering  Physical chemistry 

A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection OPEN
Slim Fourati, Aarthi Talla, Mehrad Mahmoudian, Joshua G. Burkhart, Riku Klén, Ricardo Henao, Thomas Yu, Zafer Aydın, Ka Yee Yeung, Mehmet Eren Ahsen, Reem Almugbel, Samad Jahandideh, Xiao Liang, Torbjörn E. M. Nordling, Motoki Shiga, Ana Stanescu, Robert Vogel, Emna Ben Abdallah, Farnoosh Abbas Aghababazadeh, Alicia Amadoz et al.

The response to respiratory virus exposure can currently not be predicted by pre- or early post-exposure molecular signatures. Here, the authors conduct a community-based analysis of blood gene expression from healthy individuals exposed to respiratory viruses and provide predictive models and biological insight into the physiological response.

24 October 2018 | doi: 10.1038/s41467-018-06735-8
Gene expression  Predictive markers  Viral infection 

Angular-momentum nanometrology in an ultrathin plasmonic topological insulator film OPEN
Zengji Yue, Haoran Ren, Shibiao Wei, Jiao Lin & Min Gu

Multiplexed vortex light beams are promising for optical communications, but efficient mode sorting is so far limited to bulk optics. Here the authors develop a scalable vortex beam sorter that uses a plasmonic topological insulator structure to spatially separate the modes to resolve them on a standard CMOS detector.

24 October 2018 | doi: 10.1038/s41467-018-06952-1
Nanophotonics and plasmonics  Photonic devices 

Design and self-assembly of hexahedral coordination cages for cascade reactions OPEN
Jingjing Jiao, Zijian Li, Zhiwei Qiao, Xu Li, Yan Liu, Jinqiao Dong, Jianwen Jiang & Yong Cui

Supramolecular containers are promising enzyme mimics, but they currently accommodate only a limited range of chemical transformations. Here, the authors describe coordination cages that catalyze two-component cascade reactions without relying on an external or encapsulated catalytic species.

24 October 2018 | doi: 10.1038/s41467-018-06872-0
Catalysis  Coordination chemistry  Inorganic chemistry  Supramolecular chemistry 

Inherent potential of steelmaking to contribute to decarbonisation targets via industrial carbon capture and storage OPEN
Sicong Tian, Jianguo Jiang, Zuotai Zhang & Vasilije Manovic

Carbon budget is diminishing to comply with the target under 2 °C scenario. Facing the limited capacity to improve energy efficiency, the authors show that steelmaking with inherent decarbonisation process can potentially help achieve 2050 emission reduction targets under 2 °C scenario before 2030.

24 October 2018 | doi: 10.1038/s41467-018-06886-8
Carbon capture and storage  Climate-change mitigation  Energy economics  Industry 

Efficient biosynthesis of heterodimeric C3-aryl pyrroloindoline alkaloids OPEN
Wenya Tian, Chenghai Sun, Mei Zheng, Jeffrey R. Harmer, Mingjia Yu, Yanan Zhang, Haidong Peng, Dongqing Zhu, Zixin Deng, Shi-Lu Chen, Mehdi Mobli, Xinying Jia & Xudong Qu

The hexahydropyrrolo[2, 3-b]indole (HPI) framework is found in many natural products. Here, the authors discover a P450 enzyme and develop a whole-cell biocatalysis system that produces the HPI naseseazine C (NAS-C) and 30 NAS-C analogs, several of which show neuroprotective properties.

24 October 2018 | doi: 10.1038/s41467-018-06528-z
Biocatalysis  Biosynthesis 

Ballistic tracks in graphene nanoribbons OPEN
Johannes Aprojanz, Stephen R. Power, Pantelis Bampoulis, Stephan Roche, Antti-Pekka Jauho, Harold J. W. Zandvliet, Alexei A. Zakharov & Christoph Tegenkamp

Electronic highways were realized by means of epitaxially grown graphene nanoribbons on SiC substrates. Here, the authors use spatially-resolved two-point probe and conductive AFM measurements, supplemented by tight-binding calculations, to image the one-dimensional ballistic transport channels.

24 October 2018 | doi: 10.1038/s41467-018-06940-5
Electronic properties and devices  Surfaces, interfaces and thin films 

Nuclear lactate dehydrogenase A senses ROS to produce α-hydroxybutyrate for HPV-induced cervical tumor growth OPEN
Yuan Liu, Ji-Zheng Guo, Ying Liu, Kui Wang, Wencheng Ding, Hui Wang, Xiang Liu, Shengtao Zhou, Xiao-Chen Lu, Hong-Bin Yang, Chenyue Xu, Wei Gao, Li Zhou, Yi-Ping Wang, Weiguo Hu, Yuquan Wei, Canhua Huang & Qun-Ying Lei

High-risk human papilloma virus (HR-HPV) infection is strongly associated with cervical cancer and current evidences link E7 to HPV-associated carcinogenesis. Here the authors propose a model in which the infection of epithelial cells with high risk HPV results in a burst of reactive oxygen species, translocation of LDHA to the nucleus and activation of a gene profile that supports the growth of cervical cancer.

24 October 2018 | doi: 10.1038/s41467-018-06841-7
Cancer metabolism  Cervical cancer 

Late Bayesian inference in mental transformations OPEN
Evan D. Remington, Tiffany V. Parks & Mehrdad Jazayeri

Humans compensate for sensory noise by biasing sensory estimates toward prior expectations, as predicted by models of Bayesian inference. Here, the authors show that humans perform 'late inference' downstream of sensory processing to mitigate the effects of noisy internal mental computations.

24 October 2018 | doi: 10.1038/s41467-018-06726-9
Decision  Human behaviour  Learning algorithms 

Pregnancy duration and breast cancer risk OPEN
Anders Husby, Jan Wohlfahrt, Nina Øyen & Mads Melbye

It is known that full-term pregnancies can reduce a woman's breast cancer risk. Here, the authors interrogate data from 2.3 million Danish women, showing that this protective effect arises at precisely the 34th week of the pregnancy, and replicated this finding in 1.6 million women from Norway.

23 October 2018 | doi: 10.1038/s41467-018-06748-3
Breast cancer  Cancer 

A therapeutic approach to pantothenate kinase associated neurodegeneration OPEN
Lalit Kumar Sharma, Chitra Subramanian, Mi-Kyung Yun, Matthew W. Frank, Stephen W. White, Charles O. Rock, Richard E. Lee & Suzanne Jackowski

Mutations in pantotenate kinase (PANK) cause neurodegneration. Here the authors carry out achemical screen and identify a PANK activator that is orally available, crosses the blood brain barrierand show that it effecttive in improving pathology and life span in a mouse model of the disease.

23 October 2018 | doi: 10.1038/s41467-018-06703-2
Drug discovery and development  Neurodegeneration 

Aberrant activation of non-coding RNA targets of transcriptional elongation complexes contributes to TDP-43 toxicity OPEN
Chia-Yu Chung, Amit Berson, Jason R. Kennerdell, Ashley Sartoris, Travis Unger, Sílvia Porta, Hyung-Jun Kim, Edwin R. Smith, Ali Shilatifard, Vivianna Van Deerlin, Virginia M.-Y. Lee, Alice Chen-Plotkin & Nancy M. Bonini

TDP-43 is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTD-TDP). Here, the authors identify the transcriptional elongation factor Ell as a strong modifier of TDP-43-mediated neurodegeneration through the Ell transcriptional elongation complexes LEC and SEC.

23 October 2018 | doi: 10.1038/s41467-018-06543-0
Diseases of the nervous system  Molecular neuroscience  Non-coding RNAs  Transcription 

Deciphering synergetic core-shell transformation from [Mo6O22@Ag44] to [Mo8O28@Ag50] OPEN
Zhi Wang, Hai-Feng Su, Chen-Ho Tung, Di Sun & Lan-Sun Zheng

Understanding how one metal nanocluster transforms into another is of synthetic and fundamental importance. Here, the authors use mass spectrometry to reveal an acid-induced structural transformation between two Ag clusters that proceeds via a breakage-growth-reassembly mechanism.

23 October 2018 | doi: 10.1038/s41467-018-06755-4
Coordination chemistry  Inorganic chemistry  Materials chemistry  Chemical synthesis 

Discovery of RNA-binding proteins and characterization of their dynamic responses by enhanced RNA interactome capture OPEN
Joel I. Perez-Perri, Birgit Rogell, Thomas Schwarzl, Frank Stein, Yang Zhou, Mandy Rettel, Annika Brosig & Matthias W. Hentze

RNA interactome capture allows the detailed investigation of RNA-bound proteomes. Here the authors describe enhanced RNA-interactome capture using LNA-modified probes for increased sensitivity and specificity.

23 October 2018 | doi: 10.1038/s41467-018-06557-8
Proteomics  RNA 

Raising the redox potential in carboxyphenolate-based positive organic materials via cation substitution OPEN
Alia Jouhara, Nicolas Dupré, Anne-Claire Gaillot, Dominique Guyomard, Franck Dolhem & Philippe Poizot

Organic electrode materials could enable novelty chemistry required by the new generation of batteries. Here the authors show the synthesis and electrochemical performance of Mg(Li2)-p-DHT as a lithiated cathode material that cycles at 3.4 V due to the presence of a spectator cation in the host structure.

23 October 2018 | doi: 10.1038/s41467-018-06708-x
Batteries  Energy storage 

A reference haplotype panel for genome-wide imputation of short tandem repeats OPEN
Shubham Saini, Ileena Mitra, Nima Mousavi, Stephanie Feupe Fotsing & Melissa Gymrek

Short-tandem repeats (STR), similar to single nucleotide polymorphisms (SNP), contribute to complex traits, but their ascertainment by next-generation sequencing is costly. Here, Saini et al. provide a SNP+STR haplotype reference panel that allows imputation of STRs from SNP array data.

23 October 2018 | doi: 10.1038/s41467-018-06694-0
Genetic databases  Genome informatics  Genomics  Structural variation 

Dynamic coordination of two-metal-ions orchestrates λ-exonuclease catalysis OPEN
Wonseok Hwang, Jungmin Yoo, Yuno Lee, Suyeon Park, Phuong Lien Hoang, HyeokJin Cho, Jeongmin Yu, Thi Minh Hoa Vo, Minsang Shin, Mi Sun Jin, Daeho Park, Changbong Hyeon & Gwangrog Lee

Metal ions at the active site of an enzyme act as cofactors and their dynamic fluctuations might influence enzyme activity. Here authors use single-molecule FRET to study λ-exonuclease and find that metal-ion-coordination is correlated with enzymatic reaction-steps.

23 October 2018 | doi: 10.1038/s41467-018-06750-9
Enzyme mechanisms  Kinetics  Nucleases  Single-molecule biophysics 

Design of Peptoid-peptide Macrocycles to Inhibit the β-catenin TCF Interaction in Prostate Cancer OPEN
Jeffrey A. Schneider, Timothy W. Craven, Amanda C. Kasper, Chi Yun, Michael Haugbro, Erica M. Briggs, Vladimir Svetlov, Evgeny Nudler, Holger Knaut, Richard Bonneau, Michael J. Garabedian, Kent Kirshenbaum & Susan K. Logan

Small molecules and peptide inhibitors have their benefits and faults when it comes to inhibiting protein-protein interactions. Here, the authors designed a peptoid-peptide hybrid that inhibited β-catenin/TCF interactions, leading to inhibition of Wnt signalling in models of prostate cancer.

23 October 2018 | doi: 10.1038/s41467-018-06845-3
Drug development  Peptides  Small molecules 

DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity OPEN
Xin-Xuan Lin, Ilke Sen, Georges E. Janssens, Xin Zhou, Bryan R. Fonslow, Daniel Edgar, Nicholas Stroustrup, Peter Swoboda, John R. Yates 3rd, Gary Ruvkun & Christian G. Riedel

The transcription factor DAF-16/FOXO is a downstream effector of insulin/insulin-like growth factor signaling and plays an important role in stress resistance and longevity. Here, the authors show that DAF-16/FOXO can form a complex with HLH-30/TFEB to synergistically regulate transcription of target genes in response to certain stress stimuli.

23 October 2018 | doi: 10.1038/s41467-018-06624-0
Ageing  Gene expression  Transcription 

Defective transcription elongation in a subset of cancers confers immunotherapy resistance OPEN
Vishnu Modur, Navneet Singh, Vakul Mohanty, Eunah Chung, Belal Muhammad, Kwangmin Choi, Xiaoting Chen, Kashish Chetal, Nancy Ratner, Nathan Salomonis, Matthew T. Weirauch, Susan Waltz, Gang Huang, Lisa Privette-Vinnedge, Joo-Seop Park, Edith M. Janssen & Kakajan Komurov

Transcription elongation (TE) is a key point of inducible gene expression regulation. Here, the authors report widespread TE defects (TEdeff) in a high proportion of cancers that correlate with poor immunotherapy response, highlighting TE defects as potential routes for immune resistance.

23 October 2018 | doi: 10.1038/s41467-018-06810-0
Cancer genomics  Genome informatics  Tumour immunology 

A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers OPEN
Sandra Gribi, Sophie du Bois de Dunilac, Diego Ghezzi & Stéphanie P. Lacour

Peripheral nerves have a complex physiology and it is therefore difficult to measure axonal activity in vitro. Here the authors make a nerve-on-a-chip platform to align peripheral nerves and permit measurement of conduction amplitude and velocity along several axons in a single experiment.

23 October 2018 | doi: 10.1038/s41467-018-06895-7
Action potential generation  Biomedical engineering  Biosensors  Extracellular recording 

High-performance and scalable on-chip digital Fourier transform spectroscopy OPEN
Derek M. Kita, Brando Miranda, David Favela, David Bono, Jérôme Michon, Hongtao Lin, Tian Gu & Juejun Hu

On-chip spectrometers typically have limited spectral channels and low signal to noise ratios. Here the authors introduce a digital architecture that uses switches to change the interferometer path lengths, enabling exponentially more spectral channels per circuit element and lower noise by leveraging a machine learning reconstruction algorithm.

23 October 2018 | doi: 10.1038/s41467-018-06773-2
Photonic devices  Optical spectroscopy 

Diffusion-limited reactions in dynamic heterogeneous media OPEN
Yann Lanoiselée, Nicolas Moutal & Denis S. Grebenkov

"Diffusing diffusivity" concept has been recently put forward to account for rapid structural rearrangements in soft matter and biological systems. Here the authors propose a general mathematical framework to compute the distribution of first-passage times in a dynamically heterogeneous medium.

23 October 2018 | doi: 10.1038/s41467-018-06610-6
Biological physics  Reaction kinetics and dynamics  Permeation and transport  Statistical physics 

Physical reality of the Preisach model for organic ferroelectrics OPEN
Indrė Urbanavičiūtė, Tim D. Cornelissen, Xiao Meng, Rint P. Sijbesma & Martijn Kemerink

Though the Preisach model successfully describes hysteretic switching in ferroelectrics, the physical reality of the model remains elusive. Here, the authors explained the origin of the experimental Preisach distribution and its effect on switching kinetics and materials' potential applications

23 October 2018 | doi: 10.1038/s41467-018-06717-w
Ferroelectrics and multiferroics  Information storage 

Coordinated targeting of cold and nicotinic receptors synergistically improves obesity and type 2 diabetes OPEN
Christoffer Clemmensen, Sigrid Jall, Maximilian Kleinert, Carmelo Quarta, Tim Gruber, Josefine Reber, Stephan Sachs, Katrin Fischer, Annette Feuchtinger, Angelos Karlas, Stephanie E. Simonds, Gerald Grandl, Daniela Loher, Eva Sanchez-Quant, Susanne Keipert, Martin Jastroch, Susanna M. Hofmann, Emmani B. M. Nascimento, Patrick Schrauwen, Vasilis Ntziachristos et al.

Tobacco smoking and cold exposure are environmental modulators of human energy metabolism suppressing appetite and increasing energy expenditure, respectively. Here, the authors develop a novel pharmacological strategy in which they simultaneously mimic the metabolic benefits of both phenomena through small-molecule combination therapy, and show that this treatment improves metabolic health of obese mice.

23 October 2018 | doi: 10.1038/s41467-018-06769-y
Metabolic disorders  Metabolism  Translational research 

Encoding of long-term associations through neural unitization in the human medial temporal lobe OPEN
Hernan G. Rey, Emanuela De Falco, Matias J. Ison, Antonio Valentin, Gonzalo Alarcon, Richard Selway, Mark P. Richardson & Rodrigo Quian Quiroga

In this work, the authors recorded single neurons and field potentials from the human medial temporal lobe (MTL) and show indistinguishable responses to associated stimuli. This coding mechanism provides a simple and flexible way of encoding memories in the human MTL.

22 October 2018 | doi: 10.1038/s41467-018-06870-2
Cortex  Hippocampus  Long-term memory  Neurophysiology 

A distinct isoform of ZNF207 controls self-renewal and pluripotency of human embryonic stem cells OPEN
Fang Fang, Ninuo Xia, Benjamin Angulo, Joseph Carey, Zackery Cady, Jens Durruthy-Durruthy, Theo Bennett, Vittorio Sebastiano & Renee A. Reijo Pera

Self-renewal and pluripotency of human embryonic stem cells (hESCs) depends upon the function of the transcription factor OCT4. Here, the authors identified proteins associated with the OCT4 enhancer, notably ZNF207 that maintains both pluripotency and differentiation towards ectoderm through isoform switching.

22 October 2018 | doi: 10.1038/s41467-018-06908-5
Embryonic stem cells  Proteomics  Transcription 

Identifying an efficient, thermally robust inorganic phosphor host via machine learning OPEN
Ya Zhuo, Aria Mansouri Tehrani, Anton O. Oliynyk, Anna C. Duke & Jakoah Brgoch

Identifying phosphors with good thermal stability and quantum efficiency is a prerequisite to improve the performance of white LED light sources. Here, a combined machine learning and density functional theory method is introduced to identify next generation inorganic phosphors.

22 October 2018 | doi: 10.1038/s41467-018-06625-z
Electronic structure  Inorganic LEDs  Solid-state chemistry 

Atmospheric sulfur is recycled to the crystalline continental crust during supercontinent formation OPEN
Crystal LaFlamme, Marco L. Fiorentini, Mark D. Lindsay & Thi Hao Bui

The long-term evolution of the sulfur budget in the lithosphere is poorly constrained. Here, using mass independent isotope fractionation as an indelible tracer, the authors track the pathway of sulfur from the Earth's surface to punctuated episodes of granitoid magmatism during collisional orogenesis.

22 October 2018 | doi: 10.1038/s41467-018-06691-3
Geochemistry  Geodynamics 

Heterozygous deletion of chromosome 17p renders prostate cancer vulnerable to inhibition of RNA polymerase II OPEN
Yujing Li, Yunhua Liu, Hanchen Xu, Guanglong Jiang, Kevin Van der Jeught, Yuanzhang Fang, Zhuolong Zhou, Lu Zhang, Michael Frieden, Lifei Wang, Zhenhua Luo, Milan Radovich, Bryan P. Schneider, Yibin Deng, Yunlong Liu, Kun Huang, Bin He, Jin Wang, Xiaoming He, Xinna Zhang et al.

Heterozygous loss of chromosome 17p is a common genomic event in castration-resistant prostate cancers (CRPC). Here, the authors use CRISPR-based screen to identify RBX1 as a target gene for CRPC with 17p loss and targeting RBX1 sensitizes CRPC to the treatment of α-amanitin antibody conjugates.

22 October 2018 | doi: 10.1038/s41467-018-06811-z
Cancer genomics  Targeted therapies 

Defluorosilylation of fluoroarenes and fluoroalkanes OPEN
Benqiang Cui, Shichong Jia, Etsuko Tokunaga & Norio Shibata

Transformation of strong C-F bonds into C-Si bonds is an extremely useful strategy for further derivatization of organic molecules. Here, the authors report a nickel-catalyzed strategy to convert aryl fluorides into sylylated arenes while defluorosilylation of alkyl fluorides is achieved under metal-free conditions.

22 October 2018 | doi: 10.1038/s41467-018-06830-w
Catalytic mechanisms  Homogeneous catalysis  Synthetic chemistry methodology 

Monoubiquitination of ASXLs controls the deubiquitinase activity of the tumor suppressor BAP1 OPEN
Salima Daou, Haithem Barbour, Oumaima Ahmed, Louis Masclef, Caroline Baril, Nadine Sen Nkwe, Daméhan Tchelougou, Maxime Uriarte, Eric Bonneil, Derek Ceccarelli, Nazar Mashtalir, Mika Tanji, Jean-Yves Masson, Pierre Thibault, Frank Sicheri, Haining Yang, Michele Carbone, Marc Therrien & El Bachir Affar

Additional sex combs-like (ASXLs) stimulate BAP1 deubiquitinase activity to induce tumor suppression, but how these complexes work in coordination in vivo is unclear. Here, the authors show the mutually reinforcing roles of BAP1 and ASXLs such that BAP1 promotes DEUBAD monoubiquitination of ASXL2, which in turn stimulates BAP1 DUB activity.

22 October 2018 | doi: 10.1038/s41467-018-06854-2
Mesothelioma  Tumour-suppressor proteins  Ubiquitylation 

Large increase in global storm runoff extremes driven by climate and anthropogenic changes OPEN
Jiabo Yin, Pierre Gentine, Sha Zhou, Sylvia C. Sullivan, Ren Wang, Yao Zhang & Shenglian Guo

Storm runoff extremes dominate flash flood formation and generation, posing a grand threat to ecosystems and communities across the world. Here the authors show that current projected response of these storm runoff extremes to climate and anthropogenic changes are underestimated.

22 October 2018 | doi: 10.1038/s41467-018-06765-2
Climate change  Hydrology  Natural hazards 

ZZ-dependent regulation of p62/SQSTM1 in autophagy OPEN
Yi Zhang, Su Ran Mun, Juan F. Linares, JaeWoo Ahn, Christina G. Towers, Chang Hoon Ji, Brent E. Fitzwalter, Michael R. Holden, Wenyi Mi, Xiaobing Shi, Jorge Moscat, Andrew Thorburn, Maria T. Diaz-Meco, Yong Tae Kwon & Tatiana G. Kutateladze

The autophagic receptor p62 recognizes arginylated (Nt-R) substrates through its ZZ domain (p62ZZ). Here the authors identify a p62 auto regulatory mechanism and provide structural insights into the selective recognition of Nt-R by p62ZZ and further show that Nt-R binding stimulates p62 oligomerization and macroautophagy.

22 October 2018 | doi: 10.1038/s41467-018-06878-8
Molecular biology  Solution-state NMR  X-ray crystallography 

Schedule and magnitude of reproductive investment under immune trade-offs explains sex differences in immunity OPEN
C. Jessica E. Metcalf & Andrea L. Graham

Females and males tend to emphasize different defenses against pathogens: pathogen detection and pathogen killing, respectively. Here, Metcalf and Graham show that these alternate strategies can be explained by immune trade-offs only because the sexes differ in reproductive life history.

22 October 2018 | doi: 10.1038/s41467-018-06793-y
Evolutionary ecology  Evolutionary theory  Immunology 

Scaling and data collapse from local moments in frustrated disordered quantum spin systems OPEN
Itamar Kimchi, John P. Sheckelton, Tyrel M. McQueen & Patrick A. Lee

There are many proposals for new forms of quantum matter in frustrated magnets but in practice disorder prevents the realisation of theoretically-tractable idealised models. Kimchi et al. show that recently observed scaling behavior common to several disordered quantum magnets can be understood as the emergence of a universal random-singlet regime.

22 October 2018 | doi: 10.1038/s41467-018-06800-2
Magnetic properties and materials  Phase transitions and critical phenomena 

Imaging neural activity in the ventral nerve cord of behaving adult Drosophila OPEN
Chin-Lin Chen, Laura Hermans, Meera C. Viswanathan, Denis Fortun, Florian Aymanns, Michael Unser, Anthony Cammarato, Michael H. Dickinson & Pavan Ramdya

The Drosophila ventral nerve cord (VNC) is functionally equivalent to the vertebrate spinal cord. This study reports a 2-photon imaging approach for recording neural activity in the VNC of walking and grooming adult flies.

22 October 2018 | doi: 10.1038/s41467-018-06857-z
Fluorescence imaging  Motor control 

Spin transfer torque driven higher-order propagating spin waves in nano-contact magnetic tunnel junctions OPEN
A. Houshang, R. Khymyn, H. Fulara, A. Gangwar, M. Haidar, S. R. Etesami, R. Ferreira, P. P. Freitas, M. Dvornik, R. K. Dumas & J. Åkerman

Nano-contact-based spin wave generation may enable high-frequency magnonic devices but has been limited to long wavelengths and weak signal strengths. Here the authors demonstrate high-order short-wavelength propagating spin waves with increased transmission rates and propagation lengths in magnetic tunnel junction stacks.

22 October 2018 | doi: 10.1038/s41467-018-06589-0
Magnetic properties and materials  Spintronics 

Spherical neutron polarimetry under high pressure for a multiferroic delafossite ferrite OPEN
Noriki Terada, Navid Qureshi, Laurent C. Chapon & Toyotaka Osakabe

Spherical neutron polarimetry (SNP) experiment in conjunction with high pressure condition faces many experimental difficulties. Here the authors report development of SNP with nonmagnetic hybrid anvil high pressure cell and application to the magnetoelectric multiferroic delafossite CuFeO2 system.

22 October 2018 | doi: 10.1038/s41467-018-06737-6
Ferroelectrics and multiferroics  Magnetic properties and materials 

Cyclophilin J limits inflammation through the blockage of ubiquitin chain sensing OPEN
Chunjie Sheng, Chen Yao, Ziyang Wang, Hongyuan Chen, Yu Zhao, Dazhi Xu, Haojie Huang, Wenlin Huang & Shuai Chen

Nuclear factor-kappa B (NF-κB) signaling is regulated by ubiquitin to maintain immune homeostasis. Here the authors show that a peptidylprolyl isomerase, CYPJ, blocks TAB2/3 or LUBAC ubiquitin chain sensing and suppress NF-κB activation, with CYPJ-deficiency leading to susceptibility to inflammatory stimuli.

22 October 2018 | doi: 10.1038/s41467-018-06756-3
Inflammation  Innate immunity  NF-kappaB  Ubiquitylation 

Long non-coding RNA-dependent mechanism to regulate heme biosynthesis and erythrocyte development OPEN
Jinhua Liu, Yapu Li, Jingyuan Tong, Jie Gao, Qing Guo, Lingling Zhang, Bingrui Wang, Hui Zhao, Hongtao Wang, Erlie Jiang, Ryo Kurita, Yukio Nakamura, Osamu Tanabe, James Douglas Engel, Emery H. Bresnick, Jiaxi Zhou & Lihong Shi

LncRNAs modulate diverse physiological cellular processes, however, their involvement in heme-dependent processes are not yet clear. Here the authors reveal the role of lncRNA UCA1 in erythroid cell development.

22 October 2018 | doi: 10.1038/s41467-018-06883-x
Erythropoiesis  Long non-coding RNAs 

NEDDylation promotes nuclear protein aggregation and protects the Ubiquitin Proteasome System upon proteotoxic stress OPEN
Chantal M. Maghames, Sofia Lobato-Gil, Aurelien Perrin, Helene Trauchessec, Manuel S. Rodriguez, Serge Urbach, Philippe Marin & Dimitris P. Xirodimas

Protein NEDDylation increases upon proteotoxic stress but the function of this response remains to be elucidated. Here, the authors show that NEDDylation contributes to the cellular defence against proteotoxicity by promoting nuclear protein aggregation and protecting the ubiquitin proteasome system.

22 October 2018 | doi: 10.1038/s41467-018-06365-0
Neddylation  Proteasome  Proteomic analysis  Stress signalling 

Universality of defect-skyrmion interaction profiles OPEN
Imara Lima Fernandes, Juba Bouaziz, Stefan Blügel & Samir Lounis

Clear understanding of the influence from material inhomogeneities and defects is one of the keys to achieve reliable Skyrmion based devices. Here the authors report their first principles studies on the interaction of single skyrmions with single-atom impurities and reveal its universal shape originated from the defect's electron filling.

22 October 2018 | doi: 10.1038/s41467-018-06827-5
Magnetic properties and materials  Surfaces, interfaces and thin films 

Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations OPEN
Sonya A. MacParland, Jeff C. Liu, Xue-Zhong Ma, Brendan T. Innes, Agata M. Bartczak, Blair K. Gage, Justin Manuel, Nicholas Khuu, Juan Echeverri, Ivan Linares, Rahul Gupta, Michael L. Cheng, Lewis Y. Liu, Damra Camat, Sai W. Chung, Rebecca K. Seliga, Zigong Shao, Elizabeth Lee, Shinichiro Ogawa, Mina Ogawa et al.

The development of single cell RNA sequencing technologies has been instrumental in advancing our understanding of tissue biology. Here, MacParland et al. performed single cell RNA sequencing of human liver samples, and identify distinct populations of intrahepatic macrophages that may play specific roles in liver disease.

22 October 2018 | doi: 10.1038/s41467-018-06318-7
Liver  RNA sequencing 

Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells OPEN
Seung-Chul Choi, Anton A. Titov, Georges Abboud, Howard R. Seay, Todd M. Brusko, Derry C. Roopenian, Shahram Salek-Ardakani & Laurence Morel

T cell functions depend on distinct metabolic fluxes. Here the authors show different metabolic requirements of humoral responses to self versus microbial antigens: while glucose is dispensable for antiviral Tfh and antibody responses, it is essential to mount these responses against autoantigens.

22 October 2018 | doi: 10.1038/s41467-018-06686-0
Autoimmunity  Lymphocyte activation 

Distinct population codes for attention in the absence and presence of visual stimulation OPEN
Adam C. Snyder, Byron M. Yu & Matthew A. Smith

Attention affects stimulus response gain, but its impact without sensory drive is less known. Here, the authors show that attention is coded diversely in a population and is distinct between unstimulated and stimulated contexts, providing a contrast to normalized gain models of attention.

22 October 2018 | doi: 10.1038/s41467-018-06754-5
Attention  Neural decoding 

Testicular endothelial cells are a critical population in the germline stem cell niche OPEN
Dong Ha Bhang, Bang-Jin Kim, Byung Gak Kim, Keri Schadler, Kwan-Hyuck Baek, Yong Hee Kim, Wayland Hsiao, Bi-Sen Ding, Shahin Rafii, Mitchell J. Weiss, Stella T. Chou, Thomas F. Kolon, Jill P. Ginsberg, Buom-Yong Ryu & Sandra Ryeom

Self-renewal of spermatogonial stem cells (SSC) is necessary for spermatogenesis and male fertility. Here the authors identify testicular endothelial cells (TECs) as a source of 5 key growth factors for self-renewal and expansion of human and mouse SSCs.

22 October 2018 | doi: 10.1038/s41467-018-06881-z
Calcium signalling  Stem-cell niche 

Reconfigurable infrared hyperbolic metasurfaces using phase change materials OPEN
T. G. Folland, A. Fali, S. T. White, J. R. Matson, S. Liu, N. A. Aghamiri, J. H. Edgar, R. F. Haglund Jr., Y. Abate & J. D. Caldwell

Here, the authors demonstrate that the dispersion of hyperbolic phonon polaritons can be controlled using the permittivity changes inherent in the different phases of phase change materials. This enables direct launching, reflection, transmission and refraction at the phase change material domain boundaries.

22 October 2018 | doi: 10.1038/s41467-018-06858-y
Metamaterials  Polaritons  Two-dimensional materials 

Engineering protein-protein devices for multilayered regulation of mRNA translation using orthogonal proteases in mammalian cells OPEN
Federica Cella, Liliana Wroblewska, Ron Weiss & Velia Siciliano

RNA-encoded regulatory circuits are desirable because they do not integrate in the host and are less immunogenic, but the availability of regulatory devices is limited. Here the authors develop viral protease RNA-binding proteins and protease–protease genetic circuits that ultimately regulate mRNA translation.

22 October 2018 | doi: 10.1038/s41467-018-06825-7
Molecular engineering  Protein engineering  Synthetic biology 

APOE ε2 is associated with increased tau pathology in primary tauopathy OPEN
Na Zhao, Chia-Chen Liu, Alexandra J. Van Ingelgom, Cynthia Linares, Aishe Kurti, Joshua A. Knight, Michael G. Heckman, Nancy N. Diehl, Mitsuru Shinohara, Yuka A. Martens, Olivia N. Attrebi, Leonard Petrucelli, John D. Fryer, Zbigniew K. Wszolek, Neill R. Graff-Radford, Richard J. Caselli, Monica Y. Sanchez-Contreras, Rosa Rademakers, Melissa E. Murray, Shunsuke Koga et al.

The APOE ε4 allele is a strong genetic risk factor for Alzheimer's disease, whereas the APOE ε2 allele is protective. Here the authors show that mice expressing the human APOE ε2/ε2 genotype have increased tau pathology and related behavioral deficits; they also find that the APOE ε2 allele is associated with an increased burden of tau pathology in postmortem human brains with progressive supranuclear palsy.

22 October 2018 | doi: 10.1038/s41467-018-06783-0
Alzheimer's disease  Neurodegeneration 

Global state and potential scope of investments in watershed services for large cities OPEN
Chelsie L. Romulo, Stephen Posner, Stella Cousins, Jenn Hoyle Fair, Drew E. Bennett, Heidi Huber-Stearns, Ryan C. Richards & Robert I. McDonald

Investment in watershed services programs is growing, however the factors that contribute to sustainability of such programs are unclear. Here the authors use a large database of cities around the world to show that payment schemes are more likely to be present in watersheds with more agricultural land and less protected areas.

22 October 2018 | doi: 10.1038/s41467-018-06538-x
Environmental economics  Environmental impact  Sustainability  Water resources 

Enhanced diffusion by binding to the crosslinks of a polymer gel OPEN
Carl P. Goodrich, Michael P. Brenner & Katharina Ribbeck

Gels filtering particles by interactions are a goal of nanotechnology; this is difficult when particles are larger than the mesh of the gel. Here, the authors present an equilibrium mechanism where binding dynamics of crosslinks are affected by interacting particles so that particles experience enhanced diffusion.

19 October 2018 | doi: 10.1038/s41467-018-06851-5
Biological physics  Coarse-grained models  Gels and hydrogels 

Multiparameter optimisation of a magneto-optical trap using deep learning OPEN
A. D. Tranter, H. J. Slatyer, M. R. Hush, A. C. Leung, J. L. Everett, K. V. Paul, P. Vernaz-Gris, P. K. Lam, B. C. Buchler & G. T. Campbell

Dynamics in cold atomic ensembles involve complex many-body interactions that are hard to treat analytically. Here, the authors use machine learning to optimise the cooling and trapping of neutral atoms, showing an improvement in the resulting resonant optical depth compared to more traditional solutions.

19 October 2018 | doi: 10.1038/s41467-018-06847-1
Atom optics  Computational science  Quantum information  Ultracold gases 

Complex assembly from planar and twisted π-conjugated molecules towards alloy helices and core-shell structures OPEN
Yilong Lei, Yanqiu Sun, Yi Zhang, Hongyang Zhang, Haihua Zhang, Zhengong Meng, Wai-Yeung Wong, Jiannian Yao & Hongbing Fu

Manipulating the assembly of π-conjugated organic molecules into alloys to control composition and shape remains a largely unsolved problem. Here the authors show the co-assembly of two structurally similar organic semiconductors into two-component helices by control of their growth kinetics as well as the molar ratio of the building blocks.

19 October 2018 | doi: 10.1038/s41467-018-06489-3
Molecular self-assembly  Self-assembly 

TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC OPEN
Dong Hyun Kim, Joo Seok Han, Peter Ly, Qiaozhen Ye, Moira A. McMahon, Kyungjae Myung, Kevin D. Corbett & Don W. Cleveland

The mitotic checkpoint complex (MCC) is assembled during both mitosis and interphase. Here, the authors use auxin-inducible degron tags to rapidly degrade TRIP13 and find that mitotic exit requires MCC disassembly by TRIP13-catalyzed removal of Mad2 or APC1-driven ubiquitination of Cdc20.

19 October 2018 | doi: 10.1038/s41467-018-06774-1
Checkpoints  Chromosome segregation  Mitosis 

Patterns and drivers of recent disturbances across the temperate forest biome OPEN
Andreas Sommerfeld, Cornelius Senf, Brian Buma, Anthony W. D'Amato, Tiphaine Després, Ignacio Díaz-Hormazábal, Shawn Fraver, Lee E. Frelich, Álvaro G. Gutiérrez, Sarah J. Hart, Brian J. Harvey, Hong S. He, Tomáš Hlásny, Andrés Holz, Thomas Kitzberger, Dominik Kulakowski, David Lindenmayer, Akira S. Mori, Jörg Müller, Juan Paritsis et al.

Climate change may impact forest disturbances, though local variability is high. Here, Sommerfeld et al. show that disturbance patterns across the temperate biome vary with agents and tree traits, yet large disturbances are consistently linked to warmer and drier than average conditions.

19 October 2018 | doi: 10.1038/s41467-018-06788-9
Forest ecology  Forestry 

Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes OPEN
Xiang Zhu & Matthew Stephens

In genome-wide association studies, variant-level associations are hard to identify and can be difficult to interpret biologically. Here, the authors develop a new model-based enrichment analysis method, and apply it to identify new associated genes, pathways and tissues across 31 human phenotypes.

19 October 2018 | doi: 10.1038/s41467-018-06805-x
Genome-wide association studies  Genomics  Software  Statistical methods 

Common mechanism of transcription termination at coding and noncoding RNA genes in fission yeast OPEN
Marc Larochelle, Marc-Antoine Robert, Jean-Nicolas Hébert, Xiaochuan Liu, Dominick Matteau, Sébastien Rodrigue, Bin Tian, Pierre-Étienne Jacques & François Bachand

Termination of RNA polymerase II (RNAPII) transcription is an essential step of gene expression. Here the authors provide evidence that in fission yeast termination of ncRNA genes occurs by a cleavage-dependent mechanism involving recruitment of mRNA 3′ end processing factors and requires the conserved Ysh1/CPSF-73 and Dhp1/XRN2 nucleases.

19 October 2018 | doi: 10.1038/s41467-018-06546-x
Genomic analysis  Non-coding RNAs  RNA metabolism  Transcription 

Nanodiamond autophagy inhibitor allosterically improves the arsenical-based therapy of solid tumors OPEN
Zhifen Cui, Yu Zhang, Kai Xia, Qinglong Yan, Huating Kong, Jichao Zhang, Xiaolei Zuo, Jiye Shi, Lihua Wang, Ying Zhu & Chunhai Fan

Arsenic trioxide (ATO) based therapy in solid cancers is limited. Here they repurpose nanodiamonds (NDs) as a safe and potent autophagic inhibitor to improve the efficacy of ATO-based treatment in solid tumors and show the combination therapy to work better in orthotopic liver cancer model.

19 October 2018 | doi: 10.1038/s41467-018-06749-2
Cancer  Cell biology  Nanoscience and technology 

The reaction of hydroxyl and methylperoxy radicals is not a major source of atmospheric methanol OPEN

The reaction of hydroxyl and methylperoxy radicals has recently been suggested as the source of missing methanol in the remote troposphere. Here, the authors present direct experimental measurements demonstrating the reaction leads to further underprediction of modelled methanol.

19 October 2018 | doi: 10.1038/s41467-018-06716-x
Atmospheric chemistry  Reaction kinetics and dynamics 

Mutational interactions define novel cancer subgroups OPEN
Jack Kuipers, Thomas Thurnherr, Giusi Moffa, Polina Suter, Jonas Behr, Ryan Goosen, Gerhard Christofori & Niko Beerenwinkel

Tumour heterogeneity hinders translation of large-scale genomic data into the clinic. Here the authors develop a method for the stratification of cancer patients based on the molecular gene status, including genetic interactions, rather than clinico-histological data, and apply it to TCGA data for over 8000 cases across 22 cancer types.

19 October 2018 | doi: 10.1038/s41467-018-06867-x
Cancer genomics  Statistical methods 

Dimethyl fumarate is an allosteric covalent inhibitor of the p90 ribosomal S6 kinases OPEN
Jacob Lauwring Andersen, Borbala Gesser, Erik Daa Funder, Christine Juul Fælled Nielsen, Helle Gotfred-Rasmussen, Mads Kirchheiner Rasmussen, Rachel Toth, Kurt Vesterager Gothelf, J. Simon C. Arthur, Lars Iversen & Poul Nissen

Dimethyl fumarate (DMF) is a major drug in the treatment of psoriasis and multiple sclerosis. Here the authors reveal a mechanism of RSK/MSK inhibition through covalent inhibition that can explain the observed clinical effects and the dose–response characteristics of DMF treatment.

19 October 2018 | doi: 10.1038/s41467-018-06787-w
Kinases  X-ray crystallography 

Incompatibility of the circadian protein BMAL1 and HNF4α in hepatocellular carcinoma OPEN
Baharan Fekry, Aleix Ribas-Latre, Corrine Baumgartner, Jonathan R. Deans, Christopher Kwok, Pooja Patel, Loning Fu, Rebecca Berdeaux, Kai Sun, Mikhail G. Kolonin, Sidney H. Wang, Seung-Hee Yoo, Frances M. Sladek & Kristin Eckel-Mahan

Hepatocyte nuclear factor 4 alpha (HNF4α) is regulated by different promoters to generate two isoforms, one of which functions as a tumor suppressor. Here, the authors reveal that induction of the alternative isoform in hepatocellular carcinoma inhibits the circadian clock by repressing BMAL1, and the reintroduction of BMAL1 prevents HCC tumor growth.

19 October 2018 | doi: 10.1038/s41467-018-06648-6
Cell biology  Circadian rhythms  Hepatocellular carcinoma  Liver cancer  Mechanisms of disease 

Self-powered H2 production with bifunctional hydrazine as sole consumable OPEN
Xijun Liu, Jia He, Shunzheng Zhao, Yunpeng Liu, Zhe Zhao, Jun Luo, Guangzhi Hu, Xiaoming Sun & Yi Ding

While water electrolysis provides an attractive means to produce high-energy hydrogen (H2), the process imposes significant material overpotential barriers. Here, authors employ the more-facile hydrazine splitting reaction, coupled to a hydrazine fuel cell, to perform self-powered H2 evolution.

19 October 2018 | doi: 10.1038/s41467-018-06815-9
Electrocatalysis  Fuel cells  Heterogeneous catalysis  Nanoscale materials 

Master clinical medical knowledge at certificated-doctor-level with deep learning model OPEN
Ji Wu, Xien Liu, Xiao Zhang, Zhiyang He & Ping Lv

AI is used increasingly in medical diagnostics. Here, the authors present a deep learning model that masters medical knowledge, demonstrated by it having passed the written test of the 2017 National Medical Licensing Examination in China, and can provide help with clinical diagnosis based on electronic health care records.

19 October 2018 | doi: 10.1038/s41467-018-06799-6
Computational science  Computer science  Information technology  Statistics 

Composite fermion liquid to Wigner solid transition in the lowest Landau level of zinc oxide OPEN
D. Maryenko, A. McCollam, J. Falson, Y. Kozuka, J. Bruin, U. Zeitler & M. Kawasaki

In two-dimensional electron systems, strong Coulomb interactions lead to the formation of new phases. Here the authors observe a transition between two of these correlated phases, a composite fermion liquid and Wigner solid, in a zinc oxide heterostructure.

19 October 2018 | doi: 10.1038/s41467-018-06834-6
Electronic properties and materials  Phase transitions and critical phenomena  Quantum Hall 

Neurokinin-3 receptor activation selectively prolongs atrial refractoriness by inhibition of a background K+ channel OPEN
Marieke W. Veldkamp, Guillaume S. C. Geuzebroek, Antonius Baartscheer, Arie O. Verkerk, Cees A. Schumacher, Gedeon G. Suarez, Wouter R. Berger, Simona Casini, Shirley C. M. van Amersfoorth, Koen T. Scholman, Antoine H. G. Driessen, Charly N. W. Belterman, Antoni C. G. van Ginneken, Joris R. de Groot, Jacques M. T. de Bakker, Carol Ann Remme, Bas J. Boukens & Ruben Coronel

The cardiac autonomic nervous system produces various neuropeptides, such as neurokinin substance-P (Sub-P), whose function remains largely unclear. Here, authors show that Sub-P causes a receptor-mediated prolongation of the atrial action potential through a reduced background potassium current, and prevents atrial fibrillation.

19 October 2018 | doi: 10.1038/s41467-018-06530-5
Cardiology  Cell biology  Physiology 

Mycobacterial DnaB helicase intein as oxidative stress sensor OPEN
Danielle S. Kelley, Christopher W. Lennon, Zhong Li, Michael R. Miller, Nilesh K. Banavali, Hongmin Li & Marlene Belfort

Inteins can act as post-translational environmental sensors in vivo. Here the authors characterize two inteins present in the Mycobacterium smegmatis replicative helicase DnaB that display distinct splicing behaviors and are differentially sensitive to inhibition by biological stressors and propose that splicing inhibition could modulate DnaB levels to protect the cell against replication stress.

19 October 2018 | doi: 10.1038/s41467-018-06554-x
Microbiology  Molecular biology  Proteins  X-ray crystallography 

DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing OPEN
Prasun Chakraborty, Jeffrey T. J. Huang & Kevin Hiom

Unresolved R-loops can represent a threat to genome stability. Here the authors reveal that DHX9 helicase can promote R-loop formation in the absence of splicing factors SFPQ and SF3B3.

19 October 2018 | doi: 10.1038/s41467-018-06677-1
DNA damage response  DNA synthesis  Transcription 

Structure-based redesign of docking domain interactions modulates the product spectrum of a rhabdopeptide-synthesizing NRPS OPEN
Carolin Hacker, Xiaofeng Cai, Carsten Kegler, Lei Zhao, A. Katharina Weickhmann, Jan Philip Wurm, Helge B. Bode & Jens Wöhnert

Rhabdopeptides are synthesized by non-ribosomal peptide synthetases (NRPSs) and the multiple NRPS subunits interact through docking domains (DD). Here the authors provide insights into DD interaction patterns and present the structures of three N-terminal docking domains (NDD) and a NDD-CDD complex and derive a set of recognition rules for DD interactions.

19 October 2018 | doi: 10.1038/s41467-018-06712-1
Natural products  Small molecules  Solution-state NMR 

Src regulates amino acid-mediated mTORC1 activation by disrupting GATOR1-Rag GTPase interaction OPEN
Rituraj Pal, Michela Palmieri, Arindam Chaudhury, Tiemo Jürgen Klisch, Alberto di Ronza, Joel R. Neilson, George G. Rodney & Marco Sardiello

The growth-promoting activity of mTORC1 is regulated by amino acid availability via the Rag GTPases. Here, the authors demonstrate Src-dependent control of cell size and autophagy through disruption of the Rag GTPase–GATOR1 complex and mTORC1 activation at the lysosomal surface.

19 October 2018 | doi: 10.1038/s41467-018-06844-4
Autophagy  Kinases  Nutrient signalling  TOR signalling 

Closing the gender gap in competitiveness through priming OPEN
Loukas Balafoutas, Helena Fornwagner & Matthias Sutter

Men are often more willing to compete compared to women, which may contribute to gender differences in wages and career advancement. Here, the authors show that 'power priming' - encouraging people to imagine themselves in a situation of power - can close the gender gap in competitiveness.

19 October 2018 | doi: 10.1038/s41467-018-06896-6
Decision making  Human behaviour  Psychology  Social anthropology 

HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons OPEN
Sarah Kishinevsky, Tai Wang, Anna Rodina, Sun Young Chung, Chao Xu, John Philip, Tony Taldone, Suhasini Joshi, Mary L. Alpaugh, Alexander Bolaender, Simon Gutbier, Davinder Sandhu, Faranak Fattahi, Bastian Zimmer, Smit K. Shah, Elizabeth Chang, Carmen Inda, John Koren 3rd, Nathalie G. Saurat, Marcel Leist et al.

The early molecular events that ultimately lead to neuronal cell death in pathologies such as Parkinson's disease are poorly understood. Here the authors use pluripotent stem-cell-derived human midbrain neurons and chemical biology tools to gain molecular level insight into the events induced by toxic and genetic stresses that mimic those occurring during neurodegeneration.

19 October 2018 | doi: 10.1038/s41467-018-06486-6
Mechanisms of disease  Pluripotent stem cells  Stem cells in the nervous system 

Ventral pallidum encodes relative reward value earlier and more robustly than nucleus accumbens OPEN
David Ottenheimer, Jocelyn M. Richard & Patricia H. Janak

In the ventral basal ganglia circuit, the ventral pallidum (VP) receives major inputs from the nucleus accumbens (NAc) and is involved in reward processing. Here, the authors report that, contrary to the accepted model, signals related to the relative value of reward in VP emerge before NAc and are more robust.

19 October 2018 | doi: 10.1038/s41467-018-06849-z
Feeding behaviour  Motivation  Reward 

DNA-PK inhibition synergizes with oncolytic virus M1 by inhibiting antiviral response and potentiating DNA damage OPEN
Xiao Xiao, Jiankai Liang, Chunlong Huang, Kai Li, Fan Xing, Wenbo Zhu, Ziqing Lin, Wencang Xu, Guangen Wu, Jifu Zhang, Xi Lin, Yaqian Tan, Jing Cai, Jun Hu, Xueqin Chen, Youwei Huang, Zixi Qin, Pengxin Qiu, Xingwen Su, Lijun Chen et al.

Oncolytic virotherapy is a promising strategy for cancer treatment. In this study, the authors demonstrate that DNA-dependent protein kinase (DNA-PK) inhibition sensitizes cancer cells to M1 virus and improves therapeutic effects in refractory cancer models in vivo and in patient tumour samples.

18 October 2018 | doi: 10.1038/s41467-018-06771-4
Cancer therapy  Pharmacology 

Lewis basicity generated by localised charge imbalance in noble metal nanoparticle-embedded defective metal–organic frameworks OPEN
Ying Chuan Tan & Hua Chun Zeng

Interactions between metal nanoparticles (NPs) and metal–organic frameworks (MOFs) in their composite forms have proven to exhibit beneficial properties. Here the authors present a unique approach to immobilise Pd NPs and, more importantly, to generate tunable basic sites within an anionic defective MOF.

18 October 2018 | doi: 10.1038/s41467-018-06828-4
Catalyst synthesis  Metal–organic frameworks  Organic–inorganic nanostructures 

Astrocytes integrate and drive action potential firing in inhibitory subnetworks OPEN
Tara Deemyad, Joel Lüthi & Nelson Spruston

Specific types of inhibitory neurons exhibit prolonged, high-frequency barrages of action potentials. Here, the authors show that astrocytes might mediate such barrage firing.

18 October 2018 | doi: 10.1038/s41467-018-06338-3
Astrocyte  Cellular neuroscience 

Space-time-coding digital metasurfaces OPEN
Lei Zhang, Xiao Qing Chen, Shuo Liu, Qian Zhang, Jie Zhao, Jun Yan Dai, Guo Dong Bai, Xiang Wan, Qiang Cheng, Giuseppe Castaldi, Vincenzo Galdi & Tie Jun Cui

Current digital coding metasurfaces are only space-encoded. Here, the authors propose space-time modulated digital coding metasurfaces to obtain simultaneous manipulations of electromagnetic waves and present harmonic beam steering, beam shaping, and scattering-signature control as application examples.

18 October 2018 | doi: 10.1038/s41467-018-06802-0
Electrical and electronic engineering  Metamaterials  Optical physics 

Cell shape-independent FtsZ dynamics in synthetically remodeled bacterial cells OPEN
Bill Söderström, Alexander Badrutdinov, Helena Chan & Ulf Skoglund

The FtsZ protein assembles into a structure known as 'Z-ring' at midcell for bacterial cell division. Here, Söderström et al. show that Z-ring assembly and dynamics in E. coli cells with unnatural shapes, such as squares and hearts, are generally similar to those observed in cells with normal shape.

18 October 2018 | doi: 10.1038/s41467-018-06887-7
Bacteriology  Biological fluorescence 

SMYD2 glutathionylation contributes to degradation of sarcomeric proteins OPEN
Dhanushka N. P. Munkanatta Godage, Garrett C. VanHecke, Kusal T. G. Samarasinghe, Han-Zhong Feng, Mark Hiske, Joshua Holcomb, Zhe Yang, Jian-Ping Jin, Charles S. Chung & Young-Hoon Ahn

Ischemic reperfusion or nutrient deprivation that produces reactive oxygen species can lead to a loss of muscle contractile function. Here the authors show that glutathionylation of the lysine methyltransferase SMYD2 contributes to degradation or disassembly of sarcomeres.

18 October 2018 | doi: 10.1038/s41467-018-06786-x
Cardiovascular biology  Post-translational modifications  Protein quality control 

A RNA producing DNA hydrogel as a platform for a high performance RNA interference system OPEN
Jaejung Song, Minhyuk Lee, Taeyoung Kim, Jeongkyeong Na, Yebin Jung, Gyoo Yeol Jung, Sungjee Kim & Nokyoung Park

Interfering RNA have a range of therapeutic and research based applications, issues with delivery have made systems that make siRNA in situ of interest. Here, the author report on the creation of a DNA hydrogel with improved stability and transcription efficiency over plasmid DNA.

18 October 2018 | doi: 10.1038/s41467-018-06864-0
DNA and RNA  Drug delivery  RNAi therapy  Transfection 

A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemotherapy OPEN
Guocan Yu, Shan Yu, Manik Lal Saha, Jiong Zhou, Timothy R. Cook, Bryant C. Yung, Jin Chen, Zhengwei Mao, Fuwu Zhang, Zijian Zhou, Yijing Liu, Li Shao, Sheng Wang, Changyou Gao, Feihe Huang, Peter J. Stang & Xiaoyuan Chen

It is challenging to design photosensitizers (PS) with high quantum yields generating singlet oxygen due to severe aggregation between the hydrophobic PSs. Here they develop organoplatinum(II) metallatocage-based PS to overcome these challenges and show excellent antitumor effect.

18 October 2018 | doi: 10.1038/s41467-018-06574-7
Molecular medicine  Molecular self-assembly 

Anisotropic energy transfer in crystalline chromophore assemblies OPEN
Ritesh Haldar, Marius Jakoby, Antoine Mazel, Qiang Zhang, Alexander Welle, Tawheed Mohamed, Peter Krolla, Wolfgang Wenzel, Stéphane Diring, Fabrice Odobel, Bryce S. Richards, Ian A. Howard & Christof Wöll

Exciton diffusion length and directionality are important parameters in artificial photosynthetic devices. Here, the authors present a way to make crystalline chromophore assemblies with bespoke architecture, fabricating one exhibiting anisotropic exciton transport properties.

18 October 2018 | doi: 10.1038/s41467-018-06829-3
Organic–inorganic nanostructures  Photonic crystals 

Narrow bounds for the quantum capacity of thermal attenuators OPEN
Matteo Rosati, Andrea Mari & Vittorio Giovannetti

Bounding the capacity of thermal attenuators would give a powerful instrument to describe decoherence occurring in optical fibres and free space links. Here, the authors improve on the existing upper bounds in the region of small thermal noise, which is of interest for quantum communication.

18 October 2018 | doi: 10.1038/s41467-018-06848-0
Quantum information  Quantum optics  Qubits  Theoretical physics 

Cryo-EM structures of human STEAP4 reveal mechanism of iron(III) reduction OPEN
Wout Oosterheert, Laura S. van Bezouwen, Remco N. P. Rodenburg, Joke Granneman, Friedrich Förster, Andrea Mattevi & Piet Gros

Enzymes of the six-transmembrane epithelial antigen of the prostate (STEAP) family reduce Fe3+ and Cu2+ ions to facilitate metal-ion uptake by mammalian cells. Here, authors employ single-particle cryo-EM to gain insights into the molecular principles of iron reduction by human STEAP4 .

18 October 2018 | doi: 10.1038/s41467-018-06817-7
Cryoelectron microscopy  Enzyme mechanisms 

Substantiating freedom from parasitic infection by combining transmission model predictions with disease surveys OPEN
Edwin Michael, Morgan E. Smith, Moses N. Katabarwa, Edson Byamukama, Emily Grisworld, Peace Habomugisha, Thomson Lakwo, Edridah Tukahebwa, Emmanuel S. Miri, Abel Eigege, Evelyn Ngige, Thomas R. Unnasch & Frank O. Richards

The decision when to stop an intervention is a critical component of parasite elimination programmes, but reliance on surveillance data alone can be inaccurate. Here, Michael et al. combine parasite transmission model predictions with disease survey data to more reliably determine when interventions can be stopped.

18 October 2018 | doi: 10.1038/s41467-018-06657-5
Computational models  Developing world  Epidemiology  Parasitic infection 

The genetic basis of a social polymorphism in halictid bees OPEN
Sarah D. Kocher, Ricardo Mallarino, Benjamin E. R. Rubin, Douglas W. Yu, Hopi E. Hoekstra & Naomi E. Pierce

The halictid bee Lasioglossum albipes has both solitary and eusocial individuals, making it a model for social evolution. Here, Kocher et al. identify a genetic variation associated with this social polymorphism, including a variant that can regulate the expression of an autism-associated gene, syntaxin 1a.

18 October 2018 | doi: 10.1038/s41467-018-06824-8
Behavioural genetics  Evolutionary genetics  Social evolution 

Emergence of superconductivity in the cuprates via a universal percolation process OPEN
Damjan Pelc, Marija Vučković, Mihael S. Grbić, Miroslav Požek, Guichuan Yu, Takao Sasagawa, Martin Greven & Neven Barišić

The emergence of superconductivity from the normal state in the cuprates above the transition temperature (Tc) has been controversial. Here, Pelc et al. report nonlinear conductivity, resulting from superconducting precursors only, vanishing exponentially above Tc both with temperature and with magnetic field.

18 October 2018 | doi: 10.1038/s41467-018-06707-y
Electronic properties and materials  Magnetic properties and materials  Phase transitions and critical phenomena  Quantum fluids and solids  Superconducting properties and materials 

The architecture of EGFR's basal complexes reveals autoinhibition mechanisms in dimers and oligomers OPEN
Laura C. Zanetti-Domingues, Dimitrios Korovesis, Sarah R. Needham, Christopher J. Tynan, Shiori Sagawa, Selene K. Roberts, Antonija Kuzmanic, Elena Ortiz-Zapater, Purvi Jain, Rob C. Roovers, Alireza Lajevardipour, Paul M. P. van Bergen en Henegouwen, George Santis, Andrew H. A. Clayton, David T. Clarke, Francesco L. Gervasio, Yibing Shan, David E. Shaw, Daniel J. Rolfe, Peter J. Parker et al.

To prevent ligand-independent dimerisation the epidermal growth factor receptor (EGFR) is autoinhibited by an extracellular dimer interaction. Here, the authors use several imaging technologies and simulations to provide structural insights on the inactive species and on how intracellular mutations circumvent the autoinhibition of the basal state.

18 October 2018 | doi: 10.1038/s41467-018-06632-0
Growth factor signalling  Mechanisms of disease 

mRNAs and lncRNAs intrinsically form secondary structures with short end-to-end distances OPEN
Wan-Jung C. Lai, Mohammad Kayedkhordeh, Erica V. Cornell, Elie Farah, Stanislav Bellaousov, Robert Rietmeijer, Enea Salsi, David H. Mathews & Dmitri N. Ermolenko

It was previously suggested that formation of RNA secondary structure tends to bring the 5′ and 3′ ends of RNA into close proximity. Here the authors use experimental and computational approaches to show that mRNAs and lncRNAs have an intrinsic propensity to fold into structures in which the 5′ end and 3′ end are ≤7 nm apart irrespective of length.

18 October 2018 | doi: 10.1038/s41467-018-06792-z
RNA  Single-molecule biophysics  Translation 

Structure of MHC class I-like MILL2 reveals heparan-sulfate binding and interdomain flexibility OPEN
Mizuho Kajikawa, Toyoyuki Ose, Yuko Fukunaga, Yuki Okabe, Naoki Matsumoto, Kento Yonezawa, Nobutaka Shimizu, Simon Kollnberger, Masanori Kasahara & Katsumi Maenaka

The MILL (MHC-I-like located near the leukocyte receptor complex) family is a group of related nonclassical MHC-I molecules. Here the authors present the crystal structure of MILL2, which reveals an unusual interdomain flexibility, and show that MILL2 binds heparan sulfate on the surface of fibroblasts through a basic patch.

18 October 2018 | doi: 10.1038/s41467-018-06797-8
Immunology  X-ray crystallography 
Nature Communications
2nd Annual Conference on material Science and Engineering
Dubai, United Arab Emirates
More science events from
  Latest Correspondence  
The role of MHC supertypes in promoting trans-species polymorphism remains an open question OPEN
Maciej J. Ejsmond, Karl P. Phillips, Wiesław Babik & Jacek Radwan
19 October 2018 | doi: 10.1038/s41467-018-06821-x
Evolutionary genetics  Evolutionary theory  Phylogenetics  Population genetics 
  Latest Addendum  
Addendum: A very large-scale microelectrode array for cellular-resolution electrophysiology OPEN
David Tsai, Daniel Sawyer, Adrian Bradd, Rafael Yuste & Kenneth L. Shepard
24 October 2018 | doi: 10.1038/s41467-018-06969-6
Electrophysiology  Retina  Techniques and instrumentation 
  Latest Author Corrections  
Author Correction: VAMPnets for deep learning of molecular kinetics OPEN
Andreas Mardt, Luca Pasquali, Hao Wu & Frank Noé
22 October 2018 | doi: 10.1038/s41467-018-06999-0
Machine learning  Molecular modelling  Theoretical chemistry 

Author Correction: Genetic dissection of clonal lineage relationships with hydroxytamoxifen liposomes OPEN
Ryan C. Ransom, Deshka S. Foster, Ankit Salhotra, Ruth Ellen Jones, Clement D. Marshall, Tripp Leavitt, Matthew P. Murphy, Alessandra L. Moore, Charles P. Blackshear, Elizabeth A. Brett, Derrick C. Wan & Michael T. Longaker
19 October 2018 | doi: 10.1038/s41467-018-06927-2
Cell biology  Stem cells 
  Latest Publisher Correction  
Publisher Correction: Liquid phase blending of metal-organic frameworks OPEN
Louis Longley, Sean M. Collins, Chao Zhou, Glen J. Smales, Sarah E. Norman, Nick J. Brownbill, Christopher W. Ashling, Philip A. Chater, Robert Tovey, Carola-Bibiane Schönlieb, Thomas F. Headen, Nicholas J. Terrill, Yuanzheng Yue, Andrew J. Smith, Frédéric Blanc, David A. Keen, Paul A. Midgley & Thomas D. Bennett
18 October 2018 | doi: 10.1038/s41467-018-07000-8
Glasses  Metal–organic frameworks  Soft materials 

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