Wednesday, January 17, 2018

Nature Communications -17 January 2018

Nature Communications

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17 January 2018 
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40 years of Sanger DNA sequencing

Research and Commentary reflecting on the evolution and future of Sanger DNA sequencing 

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Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis OPEN

The cellular mechanisms underlying autophagy are conserved; however it is unclear how they evolved in higher organisms. Here the authors identify two oxidation-sensitive cysteine residues in the autophagy receptor SQSTM1/p62 in vertebrates which allow activation of pro-survival autophagy in stress conditions.

17 January 2018 | doi: 10.1038/s41467-017-02746-z
Macroautophagy  Mechanisms of disease  Molecular evolution  Stress signalling 

Pteropods counter mechanical damage and dissolution through extensive shell repair OPEN
Victoria L. Peck, Rosie L. Oakes, Elizabeth M. Harper, Clara Manno & Geraint A. Tarling

Sea butterflies, or pteropods, are often presented as being at threat from ocean acidification on account of their fragile shells being susceptible to dissolution. Here the authors show that pteropods are able to perform extensive repair to damaged shells, suggesting they may not be as vulnerable as previously thought.

17 January 2018 | doi: 10.1038/s41467-017-02692-w
Climate-change ecology  Marine biology  Marine chemistry 

Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology OPEN
Alec J. Hirsch, Victoria H. J. Roberts, Peta L. Grigsby, Nicole Haese, Matthias C. Schabel, Xiaojie Wang, Jamie O. Lo, Zheng Liu, Christopher D. Kroenke, Jessica L. Smith, Meredith Kelleher, Rebecca Broeckel, Craig N. Kreklywich, Christopher J. Parkins, Michael Denton, Patricia Smith, Victor DeFilippis, William Messer, Jay A. Nelson, Jon D. Hennebold et al.

Zika virus infection during pregnancy can result in birth defects, but underlying pathogenesis at the maternal-fetal interface is unclear. Here, the authors use non-invasive in vivo imaging of Zika-infected rhesus macaques and show that infection results in abnormal oxygen transport across the placenta.

17 January 2018 | doi: 10.1038/s41467-017-02499-9
Disease model  Magnetic resonance imaging  Ultrasonography  Viral pathogenesis 

Full-field thermal imaging of quasiballistic crosstalk reduction in nanoscale devices OPEN
Amirkoushyar Ziabari, Pol Torres, Bjorn Vermeersch, Yi Xuan, Xavier Cartoixà, Alvar Torelló, Je-Hyeong Bahk, Yee Rui Koh, Maryam Parsa, Peide D. Ye, F. Xavier Alvarez & Ali Shakouri

When thermal fields in semiconductors approach the submicron scale, non-diffusive heat transport is observed where Fourier based heat transport models fail. Here, the authors use thermal imaging to visualise these thermal field variations and in turn derive a hydrodynamic heat transport model.

17 January 2018 | doi: 10.1038/s41467-017-02652-4
Condensed-matter physics  Imaging techniques  Nanoscale devices  Nanoscale materials 

Phosphorylation induced cochaperone unfolding promotes kinase recruitment and client class-specific Hsp90 phosphorylation OPEN
Ashleigh B. Bachman, Dimitra Keramisanou, Wanping Xu, Kristin Beebe, Michael A. Moses, M. V. Vasantha Kumar, Geoffrey Gray, Radwan Ebna Noor, Arjan van der Vaart, Len Neckers & Ioannis Gelis

The Hsp90 chaperone cycle is influenced by multiple phosphorylation events but their regulatory functions are poorly understood. Here, the authors show that phosphorylation and unfolding of cochaperone Cdc37 tailors the Hsp90 chaperone cycle by recruiting kinases that promote distinct phosphorylation patterns.

17 January 2018 | doi: 10.1038/s41467-017-02711-w
Chaperones  Kinases  Phosphoproteins  Solution-state NMR 

Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease OPEN
Xianyi Meng, Bettina Grötsch, Yubin Luo, Karl Xaver Knaup, Michael Sean Wiesener, Xiao-Xiang Chen, Jonathan Jantsch, Simon Fillatreau, Georg Schett & Aline Bozec

B cells are important for antigen presentation and antibody production in humoral immunity, but are also increasingly recognized for their immune regulatory functions. Here the authors show that HIF-1α, a hypoxia-induced transcription factor, is important for controlling IL-10 induction in and immune-suppressive activity of B cells.

17 January 2018 | doi: 10.1038/s41467-017-02683-x
Autoimmune diseases  B-1 cells  Gene regulation in immune cells  Interleukins 

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels OPEN
Xia Jiang, Paul F. O’Reilly, Hugues Aschard, Yi-Hsiang Hsu, J. Brent Richards, Josée Dupuis, Erik Ingelsson, David Karasik, Stefan Pilz, Diane Berry, Bryan Kestenbaum, Jusheng Zheng, Jianan Luan, Eleni Sofianopoulou, Elizabeth A. Streeten, Demetrius Albanes, Pamela L. Lutsey, Lu Yao, Weihong Tang, Michael J. Econs et al.

Vitamin D deficiency is associated with multiple human pathologic conditions. In a genome-wide association study of 79,366 individuals, Jiang et al. replicate four and identify two new genetic loci for serum levels of 25-hydroxyvitamin D and find evidence for a shared genetic basis with autoimmune diseases.

17 January 2018 | doi: 10.1038/s41467-017-02662-2
Epidemiology  Genetics research  Genome-wide association studies  Risk factors 

Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere-associated mechanosensor complex in cardiomyocytes OPEN
Judith Krysiak, Andreas Unger, Lisa Beckendorf, Nazha Hamdani, Marion von Frieling-Salewsky, Margaret M. Redfield, Cris G. dos Remedios, Farah Sheikh, Ulrich Gergs, Peter Boknik & Wolfgang A. Linke

Protein phosphatase 5 (PP5) is expressed in many cell types but its role in cardiomyocytes is unknown. Here the authors show that PP5 binds and dephosphorylates elastic titin in cardiac sarcomeres, and that PP5 is increased in heart failure, reducing cardiomyocyte compliance.

17 January 2018 | doi: 10.1038/s41467-017-02483-3
Heart failure  Muscle contraction  Phosphorylation 

133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling OPEN
Hamish Campbell, Nicholas Fleming, Imogen Roth, Sunali Mehta, Anna Wiles, Gail Williams, Claire Vennin, Nikola Arsic, Ashleigh Parkin, Marina Pajic, Fran Munro, Les McNoe, Michael Black, John McCall, Tania L. Slatter, Paul Timpson, Roger Reddel, Pierre Roux, Cristin Print, Margaret A. Baird et al.

Aberrant expression of the Δ133p53 isoform is linked to many cancers. Here, the authors utilise a model of the Δ133p53 isoform that is prone to tumours and inflammation, showing that Δ133p53 promotes tumour cell invasion by activation of the JAK-STAT and RhoA-ROCK pathways in an IL-6 dependent manner.

17 January 2018 | doi: 10.1038/s41467-017-02408-0
Metastasis  Tumour-suppressor proteins 

Multiplex glycan bead array for high throughput and high content analyses of glycan binding proteins OPEN
Sharad Purohit, Tiehai Li, Wanyi Guan, Xuezheng Song, Jing Song, Yanna Tian, Lei Li, Ashok Sharma, Boying Dun, David Mysona, Sharad Ghamande, Bunja Rungruang, Richard D. Cummings, Peng George Wang & Jin-Xiong She

The low throughput or content of current methods for the analysis of glycans-glycan binding proteins (GBPs) interactions hampers their clinical applications. Here, the authors conjugate synthesized glycans to Luminex beads to detect GBPs and apply it for the discovery of ovarian cancer biomarkers.

17 January 2018 | doi: 10.1038/s41467-017-02747-y
Biomarkers  Glycomics  High-throughput screening 

CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus OPEN
Xufeng Chen, Muhammad Aslam, Tim Gollisch, Kevin Allen & Jakob von Engelhardt

The function of receptor desensitization in vivo is not well understood. Here, the authors show that deletion of CKAMP44, an AMPAR auxiliary protein that modulates desensitization of AMPAR currents, affects synaptic facilitation at retinogeniculate synapses and visually-evoked firing in awake mice.

17 January 2018 | doi: 10.1038/s41467-017-02415-1
Molecular neuroscience  Short-term potentiation  Thalamus 

Mechanically-sensitive miRNAs bias human mesenchymal stem cell fate via mTOR signalling OPEN
Jessica E. Frith, Gina D. Kusuma, James Carthew, Fanyi Li, Nicole Cloonan, Guillermo A. Gomez & Justin J. Cooper-White

Mesenchymal stem cell (MSC) fate can be mechanically regulated by substrate stiffness but this is difficult to control in a 3D hydrogel. Here the authors identify miRNAs that change expression in response to substrate stiffness and RhoA signalling and show that they can bias MSC fate in a 3D soft hydrogel.

17 January 2018 | doi: 10.1038/s41467-017-02486-0
Biomedical engineering  Mesenchymal stem cells  miRNAs  Stem-cell differentiation 

MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A OPEN
Lauren J. Howson, Giorgio Napolitani, Dawn Shepherd, Hemza Ghadbane, Prathiba Kurupati, Lorena Preciado-Llanes, Margarida Rei, Hazel C. Dobinson, Malick M. Gibani, Karen Wei Weng Teng, Evan W. Newell, Natacha Veerapen, Gurdyal S. Besra, Andrew J. Pollard & Vincenzo Cerundolo

Most MAIT cell response to infection studies are of mice. Here the authors characterize MAIT cell population responses to Salmonella Paratyphi A infection of 25 human volunteers using TCR clonotype analysis and mass cytometry of pre-infection matched to post-infection samples.

17 January 2018 | doi: 10.1038/s41467-017-02540-x
Antimicrobial responses  Infection  T-cell receptor 

Atmospheric CO2 effect on stable carbon isotope composition of terrestrial fossil archives OPEN
Vincent J. Hare, Emma Loftus, Amy Jeffrey & Christopher Bronk Ramsey

The effect of CO2 concentrations on 13C/12C ratios in C3 plants, comprising most of Earth’s vegetation, is currently debated. Here, using ice core records and plant and animal fossils, Hare et al. find evidence for a pCO2 effect, with implications for palaeoecology and plant responses to climate change.

17 January 2018 | doi: 10.1038/s41467-017-02691-x
Biogeochemistry  Carbon cycle  Palaeoclimate  Palaeoecology 

Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells OPEN
Brent D. G. Page, Nicholas C. K. Valerie, Roni H. G. Wright, Olov Wallner, Rebecka Isaksson, Megan Carter, Sean G. Rudd, Olga Loseva, Ann-Sofie Jemth, Ingrid Almlöf, Jofre Font-Mateu, Sabin Llona-Minguez, Pawel Baranczewski, Fredrik Jeppsson, Evert Homan, Helena Almqvist, Hanna Axelsson, Shruti Regmi, Anna-Lena Gustavsson, Thomas Lundbäck et al.

NUDIX hydrolases are an important family of nucleotide-metabolizing enzymes. Here, the authors identify potent, small molecule inhibitors of NUDT5, which is implicated in ADP-ribose and 8-oxo-guanine metabolism, and confirm its role in gene regulation and proliferation in breast cancer cells.

17 January 2018 | doi: 10.1038/s41467-017-02293-7
Breast cancer  Drug discovery and development  Screening  Target validation 

The protective role of DOT1L in UV-induced melanomagenesis OPEN
Bo Zhu, Shuyang Chen, Hongshen Wang, Chengqian Yin, Changpeng Han, Cong Peng, Zhaoqian Liu, Lixin Wan, Xiaoyang Zhang, Jie Zhang, Christine G. Lian, Peilin Ma, Zhi-xiang Xu, Sharon Prince, Tao Wang, Xiumei Gao, Yujiang Shi, Dali Liu, Min Liu, Wenyi Wei et al.

The interaction of DOT1L with MLL oncogenic fusion proteins has been implicated in leukemogenesis. Here, the authors show a contrasting role for DOT1L in protecting UVR-induced melanomagenesis by facilitating DNA repair through interaction with XPC.

17 January 2018 | doi: 10.1038/s41467-017-02687-7
Epigenetics  Melanoma 

Single-molecule FRET reveals multiscale chromatin dynamics modulated by HP1α OPEN
Sinan Kilic, Suren Felekyan, Olga Doroshenko, Iuliia Boichenko, Mykola Dimura, Hayk Vardanyan, Louise C. Bryan, Gaurav Arya, Claus A. M. Seidel & Beat Fierz

Chromatin fibers undergo continuous structural rearrangements but their dynamic architecture is poorly understood. Here, the authors use single-molecule FRET to determine the structural states and interconversion kinetics of chromatin fibers, monitoring their effector protein-dependent dynamic motions.

16 January 2018 | doi: 10.1038/s41467-017-02619-5
Chromatin structure  Fluorescence resonance energy transfer  Kinetics  Single-molecule biophysics 

TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue OPEN
Laura A. Velazquez-Villegas, Alessia Perino, Vera Lemos, Marika Zietak, Mitsunori Nomura, Thijs Willem Hendrik Pols & Kristina Schoonjans

White adipose tissue can undergo a process of beiging and acquire functional characteristics similar to brown adipose tissue, including the ability to dissipate energy via uncoupled respiration. Here, Velazquez-Villegas et al. show that activation of the bile acid membrane receptor, TGR5, leads to white adipocyte beiging by promoting mitochondrial fission.

16 January 2018 | doi: 10.1038/s41467-017-02068-0
Mitochondria  Obesity 

Electron affinity of liquid water OPEN
Alex P. Gaiduk, Tuan Anh Pham, Marco Govoni, Francesco Paesani & Giulia Galli

The electron affinity of liquid water is a fundamental property which has not yet been accurately measured. Here, the authors predict this property by coupling path-integral molecular dynamics with ab initio potentials and electronic structure calculations, revisiting several estimates used in the literature.

16 January 2018 | doi: 10.1038/s41467-017-02673-z
Computational chemistry  Molecular dynamics  Physical chemistry 

Skin-inspired highly stretchable and conformable matrix networks for multifunctional sensing OPEN
Qilin Hua, Junlu Sun, Haitao Liu, Rongrong Bao, Ruomeng Yu, Junyi Zhai, Caofeng Pan & Zhong Lin Wang

Electronic skins have been developed to emulate human sensory systems, but simultaneous detection of multiple stimuli remains a big challenge due to coupling of electronic signals. Here, Hua et al. overcome this problem in a stretchable and conformable matrix network integrated with seven different modes.

16 January 2018 | doi: 10.1038/s41467-017-02685-9
Electrical and electronic engineering  Materials science  Physics 

Injury-activated glial cells promote wound healing of the adult skin in mice OPEN
Vadims Parfejevs, Julien Debbache, Olga Shakhova, Simon M. Schaefer, Mareen Glausch, Michael Wegner, Ueli Suter, Una Riekstina, Sabine Werner & Lukas Sommer

The peripheral nervous system has been implicated in wound healing. Here, Parfejevs and colleagues report that cutaneous wounding in mice induces the de-differentiation and proliferation of Schwann cells, which disseminate into the wound bed, secrete soluble factors, and promote wound healing.

16 January 2018 | doi: 10.1038/s41467-017-01488-2
Cell signalling  Mechanisms of disease  Schwann cell 

Au@Nb@H x K1-xNbO3 nanopeapods with near-infrared active plasmonic hot-electron injection for water splitting OPEN
Ying-Chu Chen, Yu-Kuei Hsu, Radian Popescu, Dagmar Gerthsen, Yan-Gu Lin & Claus Feldmann

Although near-infrared light makes up a large portion of the solar spectrum, harvesting it for photocatalytic applications remains challenging. Here the authors deposit unidirectional Au@Nb core-shell nanoparticles into tubular H x K1–xNbO3 nanoscrolls and report cooperative full solar spectrum absorption.

16 January 2018 | doi: 10.1038/s41467-017-02676-w
Nanoparticle synthesis  Nanowires  Photocatalysis 

Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine OPEN
Erin S. Calipari, Arthur Godino, Emily G. Peck, Marine Salery, Nicholas L. Mervosh, Joseph A. Landry, Scott J. Russo, Yasmin L. Hurd, Eric J. Nestler & Drew D. Kiraly

Cocaine addiction is accompanied by dysfunction in neural circuits related to reward, but it is unclear how these adaptations occur. Here, authors identify granulocyte-colony stimulating factor as a potent mediator of cocaine-induced adaptations, and show that it can alter the motivation for cocaine.

16 January 2018 | doi: 10.1038/s41467-017-01881-x
Addiction  Neuroimmunology 

The deep-subsurface sulfate reducer Desulfotomaculum kuznetsovii employs two methanol-degrading pathways OPEN
Diana Z. Sousa, Michael Visser, Antonie H. van Gelder, Sjef Boeren, Mervin M. Pieterse, Martijn W. H. Pinkse, Peter D. E. M. Verhaert, Carsten Vogt, Steffi Franke, Steffen Kümmel & Alfons J. M. Stams

Microorganisms metabolise methanol using either a methanol methyltransferase or a methanol dehydrogenase. Here, the authors use proteomics and stable isotope fractionation to show that a thermophilic sulfate-reducing bacterium, isolated from the deep subsurface, uses both pathways.

16 January 2018 | doi: 10.1038/s41467-017-02518-9
Bacterial physiology  Environmental microbiology 

A prebiotic template-directed peptide synthesis based on amyloids OPEN
Saroj K. Rout, Michael P. Friedmann, Roland Riek & Jason Greenwald

Amyloids may have played an important role in prebiotic molecular evolution but understanding replication of such information-coding molecules is still a problem. Here the authors design a model amyloid substrate and demonstrate sequence regio- and stereoselectivity during template-based replication.

16 January 2018 | doi: 10.1038/s41467-017-02742-3
Chemical origin of life  Peptides 

The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2 OPEN
Philipp Neumann, Nicolas Jaé, Andrea Knau, Simone F. Glaser, Youssef Fouani, Oliver Rossbach, Marcus Krüger, David John, Albrecht Bindereif, Phillip Grote, Reinier A. Boon & Stefanie Dimmeler

LncRNAs influence endothelial cell function via a number of mechanisms. Here the authors show that the lncRNA GATA6-AS regulates endothelial gene expression through interaction with the nuclear deaminase LOXL2, with functional consequences on endothelial-mesenchymal transition and angiogenesis.

16 January 2018 | doi: 10.1038/s41467-017-02431-1
Angiogenesis  Histone post-translational modifications  Long non-coding RNAs 

Dot1 regulates nucleosome dynamics by its inherent histone chaperone activity in yeast OPEN
Soyun Lee, Seunghee Oh, Kwiwan Jeong, Hyelim Jo, Yoonjung Choi, Hogyu David Seo, Minhoo Kim, Joonho Choe, Chang Seob Kwon & Daeyoup Lee

Dot1 is an evolutionarily conserved enzyme, responsible for histone H3K79 methylation in most eukaryotes. Here authors show that, in yeast, Dot1p has histone chaperone activity and regulates nucleosome dynamics via histone exchange in transcribed regions.

16 January 2018 | doi: 10.1038/s41467-017-02759-8
Chromatin structure  Nucleosomes 

Long-lived hot-carrier light emission and large blue shift in formamidinium tin triiodide perovskites OPEN
Hong-Hua Fang, Sampson Adjokatse, Shuyan Shao, Jacky Even & Maria Antonietta Loi

Hot carriers have excess energy that could be used to enhance solar cell efficiencies if their lifetimes are sufficiently long. Here, Fang et al. observe nanosecond hot carrier lifetime by photoluminescence in formamidinium tin triiodide perovskites which is 1000 times higher than lead based perovskites.

16 January 2018 | doi: 10.1038/s41467-017-02684-w
Electronic devices  Organic–inorganic nanostructures  Semiconductors 

Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition OPEN
Xia Liu, Wei Mo, Jian Ye, Lingyun Li, Yanping Zhang, Eddy C. Hsueh, Daniel F. Hoft & Guangyong Peng

Regulatory T (Treg) cells can induce senescence of tumour-associated effector T cells, but it is not clear how. Here the authors show that Treg cells outcompete effector T cells for glucose uptake, resulting in activation of the DNA damage response in effector T cells.

16 January 2018 | doi: 10.1038/s41467-017-02689-5
Regulatory T cells  Senescence 

Global and regional importance of the direct dust-climate feedback OPEN
Jasper F. Kok, Daniel S. Ward, Natalie M. Mahowald & Amato T. Evan

Feedbacks between desert dust and climate might have amplified past climate changes, yet their role in future climate change is unclear. Here the authors find that dust feedbacks could play a key role in the future climates of Northern Africa, the Sahel, the Mediterranean, the Middle East, and Central Asia.

16 January 2018 | doi: 10.1038/s41467-017-02620-y
Atmospheric chemistry  Climate and Earth system modelling  Projection and prediction 

Cooperating with machines OPEN
Jacob W. Crandall, Mayada Oudah, Tennom, Fatimah Ishowo-Oloko, Sherief Abdallah, Jean-François Bonnefon, Manuel Cebrian, Azim Shariff, Michael A. Goodrich & Iyad Rahwan

Artificial intelligence is now superior to humans in many fully competitive games, such as Chess, Go, and Poker. Here the authors develop a machine-learning algorithm that can cooperate effectively with humans when cooperation is beneficial but nontrivial, something humans are remarkably good at.

16 January 2018 | doi: 10.1038/s41467-017-02597-8
Computer science  Decision making 

DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer OPEN
Na Luo, Mellissa J. Nixon, Paula I. Gonzalez-Ericsson, Violeta Sanchez, Susan R. Opalenik, Huili Li, Cynthia A. Zahnow, Michael L. Nickels, Fei Liu, Mohammed N. Tantawy, Melinda E. Sanders, H. Charles Manning & Justin M. Balko

Immunotherapy often fails as a single option treatment in cancer. Here, the authors show that targeting of DNA methyltransferases, such as DNMT1, can potentiate anti-tumor immunity and response to checkpoint inhibition by increasing MHC gene expression and the recruitment of CD8+ T cells.

16 January 2018 | doi: 10.1038/s41467-017-02630-w
Breast cancer  Tumour immunology 

Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling OPEN
Josephine Elia, Grace Ungal, Charlly Kao, Alexander Ambrosini, Nilsa De Jesus-Rosario, Lene Larsen, Rosetta Chiavacci, Tiancheng Wang, Christine Kurian, Kanani Titchen, Brian Sykes, Sharon Hwang, Bhumi Kumar, Jacqueline Potts, Joshua Davis, Jeffrey Malatack, Emma Slattery, Ganesh Moorthy, Athena Zuppa, Andrew Weller et al.

Stimulant drugs are most commonly used to treat ADHD. Here, the authors demonstrate that in adolescents with ADHD who also have genetic variation in genes impacting metabotropic glutamate signaling, the non-stimulant mGluR activator fasoracetam is well tolerated and may be beneficial in alleviating symptoms of this disease.

16 January 2018 | doi: 10.1038/s41467-017-02244-2
ADHD  Genetics  Phase I trials 

Human caspase-4 detects tetra-acylated LPS and cytosolic Francisella and functions differently from murine caspase-11 OPEN
Brice Lagrange, Sacha Benaoudia, Pierre Wallet, Flora Magnotti, Angelina Provost, Fanny Michal, Amandine Martin, Flaviana Di Lorenzo, Bénédicte F. Py, Antonio Molinaro & Thomas Henry

Lipid A from some bacteria is sensed differently by humans and mice for the activation of the inflammasomes and inflammatory responses, but the mechanisms are not clear. Here, the authors show that murine caspase-11 and human caspase-4/5 contribute to this differential response via their distinct recognition of under-acylated lipid A.

16 January 2018 | doi: 10.1038/s41467-017-02682-y
Antimicrobial responses  Infection  Inflammasome  NOD-like receptors 

A bony-crested Jurassic dinosaur with evidence of iridescent plumage highlights complexity in early paravian evolution OPEN
Dongyu Hu, Julia A. Clarke, Chad M. Eliason, Rui Qiu, Quanguo Li, Matthew D. Shawkey, Cuilin Zhao, Liliana D’Alba, Jinkai Jiang & Xing Xu

A number of paravian dinosaurs have been described from the Jurassic Yanliao biota, but these have tended to be morphologically similar to Archaeopteryx. Here, Hu. describe the new paravian dinosaur, Caihong juji gen. et sp. nov., which possesses a suite of unusual skeletal and feather characteristics.

15 January 2018 | doi: 10.1038/s41467-017-02515-y
Palaeontology  Taxonomy 

Thermodynamic insight into stimuli-responsive behaviour of soft porous crystals OPEN
L. Vanduyfhuys, S. M. J. Rogge, J. Wieme, S. Vandenbrande, G. Maurin, M. Waroquier & V. Van Speybroeck

Knowledge of the thermodynamic potential is crucial to characterize the macroscopic state of soft porous crystals. Here, the authors present a generalized thermodynamic approach to construct the Helmholtz free energy and identify the conditions under which a material becomes flexible.

15 January 2018 | doi: 10.1038/s41467-017-02666-y
Structural properties  Thermodynamics 

Heliconical smectic phases formed by achiral molecules OPEN
Jordan P. Abberley, Ross Killah, Rebecca Walker, John M. D. Storey, Corrie T. Imrie, Mirosław Salamończyk, Chenhui Zhu, Ewa Gorecka & Damian Pociecha

Systems that form chiral structures from achiral molecules are not common. Here, the authors synthesise a compound consisting of asymmetric and achiral bent-shaped mesogens, which exhibit a variety of liquid crystal phases including one in which chiral structures form from achiral constituent molecules.

15 January 2018 | doi: 10.1038/s41467-017-02626-6
Liquid crystals  Molecular self-assembly  Structure of solids and liquids 

Stratospheric ozone loss over the Eurasian continent induced by the polar vortex shift OPEN
Jiankai Zhang, Wenshou Tian, Fei Xie, Martyn P. Chipperfield, Wuhu Feng, Seok-Woo Son, N. Luke Abraham, Alexander T. Archibald, Slimane Bekki, Neal Butchart, Makoto Deushi, Sandip Dhomse, Yuanyuan Han, Patrick Jöckel, Douglas Kinnison, Ole Kirner, Martine Michou, Olaf Morgenstern, Fiona M. O’Connor, Giovanni Pitari et al.

Climate change can exert a significant effect on the ozone recovery. Here, the authors show that the Arctic polar vortex shift associated with Arctic sea-ice loss could slow down ozone recovery over the Eurasian continent.

15 January 2018 | doi: 10.1038/s41467-017-02565-2
Atmospheric chemistry  Climate-change impacts 

A versatile MOF-based trap for heavy metal ion capture and dispersion OPEN
Yaguang Peng, Hongliang Huang, Yuxi Zhang, Chufan Kang, Shuangming Chen, Li Song, Dahuan Liu & Chongli Zhong

Heavy metal removal from polluted water is of global significance, but current adsorbents are limited by their specificity towards certain metals. Here the authors incorporate a non-specific and strong chelating group into a robust metal-organic framework and demonstrate its versatility for heavy metal adsorption.

15 January 2018 | doi: 10.1038/s41467-017-02600-2
Heterogeneous catalysis  Metal–organic frameworks  Organic–inorganic nanostructures  Pollution remediation 

Floats with bio-optical sensors reveal what processes trigger the North Atlantic bloom OPEN
A. Mignot, R. Ferrari & H. Claustre

The drivers of North Atlantic phytoplankton bloom have been debated for decades, partially owing to incomplete sub-surface observations. Here, Mignot et al. use robotic sensors to provide detailed observations of developing blooms and to explore the drivers of different phases of plankton growth.

15 January 2018 | doi: 10.1038/s41467-017-02143-6
Biooceanography  Marine biology  Population dynamics 

High-resolution TADs reveal DNA sequences underlying genome organization in flies OPEN
Fidel Ramírez, Vivek Bhardwaj, Laura Arrigoni, Kin Chung Lam, Björn A. Grüning, José Villaveces, Bianca Habermann, Asifa Akhtar & Thomas Manke

Although topologically associating domains (TADs) have been extensively investigated, it is not clear to what extent DNA sequence contributes to their formation. Here the authors develop software to identify high-resolution TAD boundaries and reveal their relationship to underlying DNA motifs.

15 January 2018 | doi: 10.1038/s41467-017-02525-w
Chromatin structure  Computational biology and bioinformatics  Genome 

Electric-field control of anomalous and topological Hall effects in oxide bilayer thin films OPEN
Yuki Ohuchi, Jobu Matsuno, Naoki Ogawa, Yusuke Kozuka, Masaki Uchida, Yoshinori Tokura & Masashi Kawasaki

Spintronic devices are typically controlled with magnetic fields or current injection but incorporating these mechanisms into high-density devices is difficult. Here the authors present an oxide device where the topological and anomalous Hall effects can instead be modulated using an electric field.

15 January 2018 | doi: 10.1038/s41467-017-02629-3
Electronic properties and materials  Magnetic properties and materials  Spintronics  Surfaces, interfaces and thin films 

Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis OPEN
Wen Gao, Yuhui Sun, Michelle Cai, Yujie Zhao, Wenhua Cao, Zhenhua Liu, Guanwei Cui & Bo Tang

Capsaicin prevents atherosclerotic plaque formation by activating TRPV1 cation channels, but its toxicity precludes its use in clinical settings. Here, Tang and colleagues use copper sulfide nanoparticles as a photothermal switch to locally and temporally activate TRPV1 in vascular smooth muscle cells and reduce plaque formation without apparent toxicity.

15 January 2018 | doi: 10.1038/s41467-017-02657-z
Atherosclerosis  Nanoparticles  Transient receptor potential channels 

A partially-open inward-facing intermediate conformation of LeuT is associated with Na+ release and substrate transport OPEN
Daniel S. Terry, Rachel A. Kolster, Matthias Quick, Michael V. LeVine, George Khelashvili, Zhou Zhou, Harel Weinstein, Jonathan A. Javitch & Scott C. Blanchard

Neurotransmitter:sodium symporters (NSS) modulate the duration and magnitude of signaling via the sodium-coupled reuptake of neurotransmitters. Here the authors describe quantitative single molecule imaging of ligand-induced, functional dynamics of both intracellular and extracellular surfaces of LeuT, further defining the mechanism for NSS transport.

15 January 2018 | doi: 10.1038/s41467-017-02202-y
Computational biophysics  Permeation and transport  Single-molecule biophysics 

Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing OPEN
Rahul Nahar, Weiwei Zhai, Tong Zhang, Angela Takano, Alexis J. Khng, Yin Yeng Lee, Xingliang Liu, Chong Hee Lim, Tina P. T. Koh, Zaw Win Aung, Tony Kiat Hon Lim, Lavanya Veeravalli, Ju Yuan, Audrey S. M. Teo, Cheryl X. Chan, Huay Mei Poh, Ivan M. L. Chua, Audrey Ann Liew, Dawn Ping Xi Lau, Xue Lin Kwang et al.

EGFR mutant lung adenocarcinoma (LUAD) exhibit diverse clinical outcomes in response to targeted therapies. Here the authors show that these LUADs involve a complex genomic landscape with high intratumor heterogeneity, providing insights into the evolutionary trajectory of oncogene-driven LUAD and potential mediators of EGFR TKI resistance.

15 January 2018 | doi: 10.1038/s41467-017-02584-z
Cancer genomics  Non-small-cell lung cancer 

Direct quantum process tomography via measuring sequential weak values of incompatible observables OPEN
Yosep Kim, Yong-Su Kim, Sang-Yun Lee, Sang-Wook Han, Sung Moon, Yoon-Ho Kim & Young-Wook Cho

Weak measurements constitute a powerful tool for metrology, tomography and even foundations, but in most cases could be explained classically. Here, the authors characterise a quantum channel using sequential weak value measurements of two incompatible observables utilising two-photon quantum interference.

15 January 2018 | doi: 10.1038/s41467-017-02511-2
Quantum information  Quantum optics  Single photons and quantum effects 

Reconfiguring crystal and electronic structures of MoS2 by substitutional doping OPEN
Joonki Suh, Teck Leong Tan, Weijie Zhao, Joonsuk Park, Der-Yuh Lin, Tae-Eon Park, Jonghwan Kim, Chenhao Jin, Nihit Saigal, Sandip Ghosh, Zicong Marvin Wong, Yabin Chen, Feng Wang, Wladyslaw Walukiewicz, Goki Eda & Junqiao Wu

Substitutional doping is well-established in traditional semiconductors but has not been extensively explored in two-dimensional semiconductors. Here, the authors investigate the structural and electronic effects of Nb doping in MoS2 crystals.

15 January 2018 | doi: 10.1038/s41467-017-02631-9
Electronic properties and materials  Surfaces, interfaces and thin films  Two-dimensional materials 

Structural basis for chitin acquisition by marine Vibrio species OPEN
Anuwat Aunkham, Michael Zahn, Anusha Kesireddy, Karunakar Reddy Pothula, Albert Schulte, Arnaud Baslé, Ulrich Kleinekathöfer, Wipa Suginta & Bert van den Berg

Chitin degrading bacteria are important for marine ecosystems. Here the authors structurally and functionally characterize the Vibrio harveyi outer membrane diffusion channel chitoporin and give mechanistic insights into chito-oligosaccharide uptake.

15 January 2018 | doi: 10.1038/s41467-017-02523-y
Bacterial structural biology  Carbohydrates  Permeation and transport  X-ray crystallography 

An equation-of-state-meter of quantum chromodynamics transition from deep learning OPEN
Long-Gang Pang, Kai Zhou, Nan Su, Hannah Petersen, Horst Stöcker & Xin-Nian Wang

The large data generated in heavy-ion collision experiments require careful analysis to understand the physics. Here the authors use the deep-learning method to sort equation of states in QCD transition and analyze the simulated data sets mimicking the heavy-ion collision experiments.

15 January 2018 | doi: 10.1038/s41467-017-02726-3
Fluid dynamics  Information theory and computation  Theoretical nuclear physics 

Raman enhancement on ultra-clean graphene quantum dots produced by quasi-equilibrium plasma-enhanced chemical vapor deposition OPEN
Donghua Liu, Xiaosong Chen, Yibin Hu, Tai Sun, Zhibo Song, Yujie Zheng, Yongbin Cao, Zhi Cai, Min Cao, Lan Peng, Yuli Huang, Lei Du, Wuli Yang, Gang Chen, Dapeng Wei, Andrew Thye Shen Wee & Dacheng Wei

Surface-enhanced Raman spectroscopy (SERS) is a promising technology for sensitive optical sensors, generally using rough metal films. Here, Liu et al. synthesize high-quality graphene quantum dot films which offer a large SERS enhancement due to a strong light-matter interaction with Van Hove singularities.

15 January 2018 | doi: 10.1038/s41467-017-02627-5
Raman spectroscopy  SERS  Synthesis and processing  Synthesis of graphene 

Characterizing the dynamics underlying global spread of epidemics OPEN
Lin Wang & Joseph T. Wu

Understanding global epidemics spread is crucial for preparedness and response. Here the authors introduce an analytical framework to study epidemic spread on air transport networks, and demonstrate its power to estimate key epidemic parameters by application to the recent influenza pandemic and Ebola outbreak.

15 January 2018 | doi: 10.1038/s41467-017-02344-z
Complex networks  Epidemiology  Infectious diseases 

Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits OPEN
Rafael Renteria, Emily T. Baltz & Christina M. Gremel

Drug dependence shifts the balance in action selection away from goal-directed to habitual responding. Here, the authors report that chronic passive exposure to alcohol leads to suppression of orbitofrontal cortex inputs to dorsomedial striatum resulting in downregulation of goal-directed behavior.

15 January 2018 | doi: 10.1038/s41467-017-02615-9
Operant learning  Reward 

Abnormal phase transition between two-dimensional high-density liquid crystal and low-density crystalline solid phases OPEN
Wenbin Li, Longjuan Kong, Baojie Feng, Huixia Fu, Hui Li, Xiao Cheng Zeng, Kehui Wu & Lan Chen

Intermolecular interactions have a crucial role in the adsorption of molecules on a surface, however their role in promoting phase transitions is less well known. Here, the authors report an abnormal phase transition between a high-density liquid crystal and low-density solid in the case of carbon monoxide on Cu(111), driven by intermolecular interactions and entropy.

15 January 2018 | doi: 10.1038/s41467-017-02634-6
Phase transitions and critical phenomena  Surface assembly  Thermodynamics  Two-dimensional materials 

USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A OPEN
Michael Uckelmann, Ruth M. Densham, Roy Baas, Herrie H. K. Winterwerp, Alexander Fish, Titia K. Sixma & Joanna R. Morris

BRCA1 ligase activity is tightly regulated to maintain genome stability and confer DNA double strand repair. Here the authors identify USP48 as a H2A deubiquitinating enzyme that acts as a BRCA1 E3 ligase antagonist and characterize its role during DNA repair.

15 January 2018 | doi: 10.1038/s41467-017-02653-3
Breast cancer  Homologous recombination 

Experimental quantum simulation of fermion-antifermion scattering via boson exchange in a trapped ion OPEN
Xiang Zhang, Kuan Zhang, Yangchao Shen, Shuaining Zhang, Jing-Ning Zhang, Man-Hong Yung, Jorge Casanova, Julen S. Pedernales, Lucas Lamata, Enrique Solano & Kihwan Kim

Simulation of quantum field theory using quantum systems would in principle allow avoidance of the exponential overhead required for classical simulations. Here, the authors use a multilevel trapped ion to simulate the processes of self-interaction and particle-antiparticle creation/annihilation.

15 January 2018 | doi: 10.1038/s41467-017-02507-y
Quantum optics  Quantum simulation  Theoretical particle physics 

Radical asymmetric intramolecular α-cyclopropanation of aldehydes towards bicyclo[3.1.0]hexanes containing vicinal all-carbon quaternary stereocenters OPEN
Liu Ye, Qiang-Shuai Gu, Yu Tian, Xiang Meng, Guo-Cong Chen & Xin-Yuan Liu

Synthesis of cyclopropanes bearing vicinal all-carbon quaternary stereocenters poses synthetic challenges. Here, the authors report an intramolecular radical cyclopropanation with a copper/amine cooperative catalytic system for the efficient construction of bicyclo[3.1.0]hexane skeletons, also enantioselectively.

15 January 2018 | doi: 10.1038/s41467-017-02231-7
Asymmetric catalysis  Synthetic chemistry methodology  Reaction mechanisms 

Monitoring single-cell gene regulation under dynamically controllable conditions with integrated microfluidics and software OPEN
Matthias Kaiser, Florian Jug, Thomas Julou, Siddharth Deshpande, Thomas Pfohl, Olin K. Silander, Gene Myers & Erik van Nimwegen

How gene regulatory pathways control cell fate decisions in single cells is not fully understood. Here the authors present an integrated dual-input microfluidic chip and a linked analysis software, enabling tracking of gene regulatory responses of single bacterial cells to changing conditions.

15 January 2018 | doi: 10.1038/s41467-017-02505-0
Image processing  Regulatory networks  Single-cell imaging 

Deubiquitinase USP13 dictates MCL1 stability and sensitivity to BH3 mimetic inhibitors OPEN
Shengzhe Zhang, Meiying Zhang, Ying Jing, Xia Yin, Pengfei Ma, Zhenfeng Zhang, Xiaojie Wang, Wen Di & Guanglei Zhuang

MCL1, a pro-survival BCL-2 related protein with rapid turnover rate, is often dysregulated in cancers. Here, the authors show that MCL1’s stability is regulated by deubiquitinase USP13, and its inhibition sensitises tumor cells to BH3 mimetic inhibitors.

15 January 2018 | doi: 10.1038/s41467-017-02693-9
Cancer therapy  Oncogenes 

Escape from thymic deletion and anti-leukemic effects of T cells specific for hematopoietic cell-restricted antigen OPEN
Ji-Min Ju, Min Ho Jung, Giri Nam, Woojin Kim, Sehwa Oh, Hyun Duk Kim, Joo Young Kim, Jun Chang, Sung Hak Lee, Gyeong Sin Park, Chang-Ki Min, Dong-Sup Lee, Moon Gyo Kim, Kyungho Choi & Eun Young Choi

Antigen distribution patterns affect thymic negative selection. Here, the authors show that incomplete thymic negative selection occurs to T cells for hematopoietic cell-restricted antigen H60 in mice, driving graft-versus-leukemia after H60-mismatched bone marrow transplantation.

15 January 2018 | doi: 10.1038/s41467-017-02665-z
Bone marrow transplantation  Cytotoxic T cells 

Sub-kb Hi-C in D. melanogaster reveals conserved characteristics of TADs between insect and mammalian cells OPEN
Qi Wang, Qiu Sun, Daniel M. Czajkowsky & Zhifeng Shao

Topologically associating domain (TAD) boundaries in flies seem to be different from those in mammals. Here, the authors use Hi-C with sub-kb resolution to identify about 4000 TADs in flies, most demarcated by the insulator complexes BEAF-32/CP190 or BEAF-32/Chromator like CTCF/cohesin in mammals.

15 January 2018 | doi: 10.1038/s41467-017-02526-9
Chromatin structure  Chromosomes  Genome 

Strongly exchange-coupled and surface-state-modulated magnetization dynamics in Bi2Se3/yttrium iron garnet heterostructures OPEN
Y. T. Fanchiang, K. H. M. Chen, C. C. Tseng, C. C. Chen, C. K. Cheng, S. R. Yang, C. N. Wu, S. F. Lee, M. Hong & J. Kwo

Understanding the effects of topological insulators on magnetization dynamics of adjacent magnetic materials is essential for novel spintronic devices. Here, Fanchiang et al. report thickness dependence of interfacial in-plane magnetic anisotropy and damping enhancement in Bi2Se3/yttrium iron garnet (YIG) bilayers, indicating an important role of topological surface states in the magnetization dynamics of YIG.

15 January 2018 | doi: 10.1038/s41467-017-02743-2
Ferromagnetism  Spintronics  Topological insulators 

Evolutionary history of Coleoptera revealed by extensive sampling of genes and species OPEN
Shao-Qian Zhang, Li-Heng Che, Yun Li, Dan Liang, Hong Pang, Adam Ślipiński & Peng Zhang

The phylogeny of beetles, which represent ~25% of known extant animal species, has been a challenge to resolve. Here, Zhang et al. infer a time-calibrated phylogeny for Coleoptera based on 95 protein-coding genes in 373 species and suggest an association between the hyperdiversification of beetles and the rise of angiosperms.

15 January 2018 | doi: 10.1038/s41467-017-02644-4
Entomology  Phylogenetics 

Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer OPEN
Tian Fang, Hongwei Lv, Guishuai Lv, Ting Li, Changzheng Wang, Qin Han, Lexing Yu, Bo Su, Linna Guo, Shanna Huang, Dan Cao, Liang Tang, Shanhua Tang, Mengchao Wu, Wen Yang & Hongyang Wang

How tumor cells control metastatic niche formation is not fully understood. Here, the authors show in a lung metastatic niche, high-metastatic hepatocellular carcinoma cells secrete exosomal miR-1247-3p that leads to activation of β1-integrin-NF-κBsignalling, converting fibroblasts to cancer-associated fibroblasts.

15 January 2018 | doi: 10.1038/s41467-017-02583-0
Cancer microenvironment  Hepatocellular carcinoma 

Phosphorylation-induced conformation of β2-adrenoceptor related to arrestin recruitment revealed by NMR OPEN
Yutaro Shiraishi, Mei Natsume, Yutaka Kofuku, Shunsuke Imai, Kunio Nakata, Toshimi Mizukoshi, Takumi Ueda, Hideo Iwaï & Ichio Shimada

Upon stimulation by agonist binding, the C-terminal regions of G-protein-coupled receptors (GPCRs) become phosphorylated by GPCR kinases, and phosphorylated GPCRs bind arrestin. Here the authors give structural insights into the phosphorylation induced conformational changes in GPCRs by performing NMR studies with the β2-adrenoceptor.

15 January 2018 | doi: 10.1038/s41467-017-02632-8
G protein-coupled receptors  Solution-state NMR 

Ligands with 1,10-phenanthroline scaffold for highly regioselective iron-catalyzed alkene hydrosilylation OPEN
Meng-Yang Hu, Qiao He, Song-Jie Fan, Zi-Chen Wang, Luo-Yan Liu, Yi-Jiang Mu, Qian Peng & Shou-Fei Zhu

Hydrosilylation of alkenes poses substantial challenges in terms of regioselectivity. Here, the authors report iron complexes with 1,10-phenantroline ligand scaffolds which  display benzylic selectivity in the hydrosilylation of internal alkenes and Markovnikov selectivity with terminal styrenes and 1,3-dienes.

15 January 2018 | doi: 10.1038/s41467-017-02472-6
Homogeneous catalysis  Synthetic chemistry methodology  Sustainability 

Intelligent image-based in situ single-cell isolation OPEN
Csilla Brasko, Kevin Smith, Csaba Molnar, Nora Farago, Lili Hegedus, Arpad Balind, Tamas Balassa, Abel Szkalisity, Farkas Sukosd, Katalin Kocsis, Balazs Balint, Lassi Paavolainen, Marton Z. Enyedi, Istvan Nagy, Laszlo G. Puskas, Lajos Haracska, Gabor Tamas & Peter Horvath

The isolation of single cells while retaining context is important for quantifying cellular heterogeneity but technically challenging. Here, the authors develop a high-throughput, scalable workflow for microscopy-based single cell isolation using machine-learning, high-throughput microscopy and laser capture microdissection.

15 January 2018 | doi: 10.1038/s41467-017-02628-4
Image processing  Machine learning  Optical imaging  Single-cell imaging 

Causal associations between risk factors and common diseases inferred from GWAS summary data OPEN
Zhihong Zhu, Zhili Zheng, Futao Zhang, Yang Wu, Maciej Trzaskowski, Robert Maier, Matthew R. Robinson, John J. McGrath, Peter M. Visscher, Naomi R. Wray & Jian Yang

Genetic methods are useful to test whether risk factors are causal for or consequence of disease. Here, Zhu et al. develop a generalized summary-based Mendelian Randomization (GSMR) method which uses summary-level data from GWAS to test for causal associations of health risk factors with common diseases.

15 January 2018 | doi: 10.1038/s41467-017-02317-2
Genome-wide association studies  Risk factors  Statistical methods 

Strong modulation of second-harmonic generation with very large contrast in semiconducting CdS via high-field domain OPEN
Ming-Liang Ren, Jacob S. Berger, Wenjing Liu, Gerui Liu & Ritesh Agarwal

Dynamically controlling nonlinear signals with large modulation amplitudes is a challenging task. Here, Ren et al. demonstrate high-contrast electric switching of the second-order nonlinear coefficient in CdS nanobelts and explain the observed transistor-like behavior based on high-field domains.

15 January 2018 | doi: 10.1038/s41467-017-02548-3
Nanophotonics and plasmonics  Nonlinear optics 

In situ single-shot diffractive fluence mapping for X-ray free-electron laser pulses OPEN
Michael Schneider, Christian M. Günther, Bastian Pfau, Flavio Capotondi, Michele Manfredda, Marco Zangrando, Nicola Mahne, Lorenzo Raimondi, Emanuele Pedersoli, Denys Naumenko & Stefan Eisebitt

Free electron laser beam profile characterization is usually performed separately from the actual measurements and this leads to considerable uncertainty in the results. Here the authors demonstrate the simultaneous measurement of the FEL beam profile with the experiment by using integrated gratings.

15 January 2018 | doi: 10.1038/s41467-017-02567-0
Free-electron lasers  Imaging and sensing  X-rays 

AICDA drives epigenetic heterogeneity and accelerates germinal center-derived lymphomagenesis OPEN
Matt Teater, Pilar M. Dominguez, David Redmond, Zhengming Chen, Daisuke Ennishi, David W. Scott, Luisa Cimmino, Paola Ghione, Jayanta Chaudhuri, Randy D. Gascoyne, Iannis Aifantis, Giorgio Inghirami, Olivier Elemento, Ari Melnick & Rita Shaknovich

In diffuse large B-cell lymphoma (DLBCL) increased epigenetic heterogeneity in the form of cytosine methylation is known to link to a poor clinical outcome. Here, the authors show that AICDA, an enzyme required for DLBCL pathogenesis, increases cytosine methylation heterogeneity.

15 January 2018 | doi: 10.1038/s41467-017-02595-w
B-cell lymphoma  Epigenomics 

Brain activity patterns in high-throughput electrophysiology screen predict both drug efficacies and side effects OPEN
Peter M. Eimon, Mostafa Ghannad-Rezaie, Gianluca De Rienzo, Amin Allalou, Yuelong Wu, Mu Gao, Ambrish Roy, Jeffrey Skolnick & Mehmet Fatih Yanik

One challenge in drug screening for neurological disorders is how to accurately capture disease pathology and side effects. Here, the authors developed a multi-channel recording platform based on a zebrafish genetic model of epilepsy to screen for antiepileptic drugs.

15 January 2018 | doi: 10.1038/s41467-017-02404-4
Epilepsy  High-throughput screening  Molecular neuroscience 

Deregulated PP1α phosphatase activity towards MAPK activation is antagonized by a tumor suppressive failsafe mechanism OPEN
Ming Chen, Lixin Wan, Jiangwen Zhang, Jinfang Zhang, Lourdes Mendez, John G. Clohessy, Kelsey Berry, Joshua Victor, Qing Yin, Yuan Zhu, Wenyi Wei & Pier Paolo Pandolfi

Alterations in the MAPK pathway are common in cancers, yet mutations are rarely found in patients. Here the authors find genomic amplifications of the PPP1CA gene in advanced and metastatic prostate cancer and identify a role for this phosphatase in the positive regulation of ERK signalling.

15 January 2018 | doi: 10.1038/s41467-017-02272-y
Growth factor signalling  Prostate cancer 

Pixelated spatial gene expression analysis from tissue OPEN
A. Ganguli, A. Ornob, N. Spegazzini, Y. Liu, G. Damhorst, T. Ghonge, B. Thornton, C. J. Konopka, W. Dobrucki, S. E. Clare, R. Bhargava, A. M. Smith, F. Kosari & R. Bashir

Spatial localization of genetic information is important for tissue heterogeneity but difficult to capture with current analytical techniques. Here the authors present “Pixelated RT-LAMP”, an approach that uses parallel on-chip reactions to provide the distribution of target sequences directly from tissue.

15 January 2018 | doi: 10.1038/s41467-017-02623-9
Biochemical assays  Lab-on-a-chip  Transcriptomics 

Structure of a MacAB-like efflux pump from Streptococcus pneumoniae OPEN
Hong-Bo Yang, Wen-Tao Hou, Meng-Ting Cheng, Yong-Liang Jiang, Yuxing Chen & Cong-Zhao Zhou

Bacterial ATP-binding cassette (ABC)-type efflux pumps are involved in the resistance of antibiotics and antimicrobial peptides. Here authors report the crystal structures and ATPase activity of the MacAB-like efflux pump from Streptococcus pneumonia and describe a putative substrate transport mechanism.

15 January 2018 | doi: 10.1038/s41467-017-02741-4
Membrane proteins  X-ray crystallography 

Unusual multiscale mechanics of biomimetic nanoparticle hydrogels OPEN
Yunlong Zhou, Pablo F. Damasceno, Bagganahalli S. Somashekar, Michael Engel, Falin Tian, Jian Zhu, Rui Huang, Kyle Johnson, Carl McIntyre, Kai Sun, Ming Yang, Peter F. Green, Ayyalusamy Ramamoorthy, Sharon C. Glotzer & Nicholas A. Kotov

Achieving simultaneous high storage and loss moduli in gels is difficult due to the opposite chemical structure requirements needed for such properties. Here the authors show a spectrum of gels containing CdTe nanoparticles stabilized by glutathione that have such properties which can be rationalised through the developed model.

12 January 2018 | doi: 10.1038/s41467-017-02579-w
Gels and hydrogels  Nanoparticles  Self-assembly 

20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner through FFAR1 OPEN
Sorin Tunaru, Remy Bonnavion, Isabell Brandenburger, Jens Preussner, Dominique Thomas, Klaus Scholich & Stefan Offermanns

FFAR1 receptor is highly expressed in beta cells and its activation has been suggested as therapy against type-2 diabetes. Here, Tunaru et al. show that 20-hydroxyeicosatetraenoic acid, produced within the islets upon glucose stimulation, acts in an autocrine manner to stimulate insulin secretion via FFAR1 activation.

12 January 2018 | doi: 10.1038/s41467-017-02539-4
Homeostasis  Type 2 diabetes 

Target engagement imaging of PARP inhibitors in small-cell lung cancer OPEN
Brandon Carney, Susanne Kossatz, Benjamin H. Lok, Valentina Schneeberger, Kishore K. Gangangari, Naga Vara Kishore Pillarsetty, Wolfgang A. Weber, Charles M. Rudin, John T. Poirier & Thomas Reiner

Treatment of small-cell lung cancer remains a challenge due to multiple mechanisms of resistance to current therapies; measuring patient response is crucial in adapting and choosing adequate treatment. Here the authors develop a strategy to visualise in vivo dynamics of a class of widely used PARP inhibitors.

12 January 2018 | doi: 10.1038/s41467-017-02096-w
Positron-emission tomography  Small-cell lung cancer  Target identification 

Pathway design using de novo steps through uncharted biochemical spaces OPEN
Akhil Kumar, Lin Wang, Chiam Yu Ng & Costas D. Maranas

Existing pathway design tools make use of existing reactions from databases or successively apply retrosynthetic rules. novoStoic provides an integrated optimization-based framework combining known reactions with novel steps in pathway design allowing for constraints on thermodynamic feasibility, product yield, pathway length and number of novel steps.

12 January 2018 | doi: 10.1038/s41467-017-02362-x
Biochemical reaction networks  Metabolic engineering 

Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles OPEN
Eduardo Reátegui, Kristan E. van der Vos, Charles P. Lai, Mahnaz Zeinali, Nadia A. Atai, Berent Aldikacti, Frederick P. Floyd Jr., Aimal H. Khankhel, Vishal Thapar, Fred H. Hochberg, Lecia V. Sequist, Brian V. Nahed, Bob S. Carter, Mehmet Toner, Leonora Balaj, David T. Ting, Xandra O. Breakefield & Shannon L. Stott

Extracellular vesicles can carry many different types of biological cargo and have been investigated as a biomarker for cancer diagnosis. Here the authors develop a microfluidic platform for rapid and sensitive isolation of tumor-specific extracellular vesicles.

12 January 2018 | doi: 10.1038/s41467-017-02261-1
Biomedical engineering  Lab-on-a-chip  Tumour biomarkers 

Architecture of a mammalian glomerular domain revealed by novel volume electroporation using nanoengineered microelectrodes OPEN
D. Schwarz, M. Kollo, C. Bosch, C. Feinauer, I. Whiteley, T. W. Margrie, T. Cutforth & A. T. Schaefer

Microcircuit tracing reconstructions often rely on statistical labeling that may not detect all inputs and outputs of a microcircuit. Here the authors employ a novel electroporation approach to densely label neurons and demonstrate its ability to identify sparse anatomical features in the olfactory glomerulus.

12 January 2018 | doi: 10.1038/s41467-017-02560-7
Cellular neuroscience  Neural circuits  Olfactory bulb  Techniques and instrumentation 

Disulfide isomerization reactions in titin immunoglobulin domains enable a mode of protein elasticity OPEN
David Giganti, Kevin Yan, Carmen L. Badilla, Julio M. Fernandez & Jorge Alegre-Cebollada

Titin regulates myocyte stiffness through uncoiling and unfolding but these two processes cannot fully explain its elasticity. Here, the authors use atomic force microscopy to study the properties of titin disulfide bonds, showing that disulfide isomerization represents a third mode of titin elasticity.

12 January 2018 | doi: 10.1038/s41467-017-02528-7
Atomic force microscopy  Contractile proteins  Single-molecule biophysics 

Carbon-doped SnS2 nanostructure as a high-efficiency solar fuel catalyst under visible light OPEN
Indrajit Shown, Satyanarayana Samireddi, Yu-Chung Chang, Raghunath Putikam, Po-Han Chang, Amr Sabbah, Fang-Yu Fu, Wei-Fu Chen, Chih-I Wu, Tsyr-Yan Yu, Po-Wen Chung, M. C. Lin, Li-Chyong Chen & Kuei-Hsien Chen

Photocatalytic reduction of CO2 to hydrocarbons is a promising route to both CO2 utilization and renewable fuel production. Here the authors identify that carbon-doped SnS2 possesses a high catalytic efficiency towards CO2 reduction owing to low photogenerated charge recombination rates.

12 January 2018 | doi: 10.1038/s41467-017-02547-4
Nanoscale materials  Photocatalysis  Solar fuels 

Picometer polar atomic displacements in strontium titanate determined by resonant X-ray diffraction OPEN
Carsten Richter, Matthias Zschornak, Dmitri Novikov, Erik Mehner, Melanie Nentwich, Juliane Hanzig, Semën Gorfman & Dirk C. Meyer

It is a challenge to measure changes in the crystal structures in picometer scale and the associated phase. Here the authors demonstrate the lattice expansion and polar distortions of oxygen deficient SrTiO3 using a resonance X-ray scattering technique.

12 January 2018 | doi: 10.1038/s41467-017-02599-6
Characterization and analytical techniques  Ferroelectrics and multiferroics  X-rays 

NF-κB inducing kinase is a therapeutic target for systemic lupus erythematosus OPEN
Hans D. Brightbill, Eric Suto, Nicole Blaquiere, Nandhini Ramamoorthi, Swathi Sujatha-Bhaskar, Emily B. Gogol, Georgette M. Castanedo, Benjamin T. Jackson, Youngsu C. Kwon, Susan Haller, Justin Lesch, Karin Bents, Christine Everett, Pawan Bir Kohli, Sandra Linge, Laura Christian, Kathy Barrett, Allan Jaochico, Leonid M. Berezhkovskiy, Peter W. Fan et al.

Clinical trials of BAFF blockade with belimumab have shown partial efficacy for the treatment of systemic lupus erythematosus (SLE), so other therapeutic options are required. Here, the authors present a new small molecule inhibitor that targets NIK with a similar efficacy to BAFF inhibition in two mouse models of SLE.

12 January 2018 | doi: 10.1038/s41467-017-02672-0
Systemic lupus erythematosus  Target validation 

Fibre-optic metadevice for all-optical signal modulation based on coherent absorption OPEN
Angelos Xomalis, Iosif Demirtzioglou, Eric Plum, Yongmin Jung, Venkatram Nalla, Cosimo Lacava, Kevin F. MacDonald, Periklis Petropoulos, David J. Richardson & Nikolay I. Zheludev

Here, the authors show that integration of metamaterial and optical fibre technologies enables all-optical XOR, NOT and AND logical functions that are performed at up to 40 gigabits per second with few femtojoules per bit energy consumption within a coherent fully fiberized network.

12 January 2018 | doi: 10.1038/s41467-017-02434-y
Fibre optics and optical communications  Metamaterials  Nanophotonics and plasmonics 

Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability OPEN
Jamie J. L. Williams, Nasser Alotaiq, William Mullen, Richard Burchmore, Libin Liu, George S. Baillie, Fred Schaper, Paul F. Pilch & Timothy M. Palmer

SOCS3 is an important negative feedback inhibitor of JAK–STAT-mediated cytokine signalling. Here the authors implicate cavin-1 — an essential component of caveolae — in the recruitment of SOCS3 to the plasma membrane to prevent sustained cytokine receptor signalling.

12 January 2018 | doi: 10.1038/s41467-017-02585-y
Growth factor signalling  Interleukins 

Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168 OPEN
Tomio S. Takahashi, Yoshihiro Hirade, Aya Toma, Yusuke Sato, Atsushi Yamagata, Sakurako Goto-Ito, Akiko Tomita, Shinichiro Nakada & Shuya Fukai

E3 ubiquitin ligase RNF168 is important for the repair of DNA double-strand breaks and recognizes ubiquitylated targets through two Ub-dependent DSB recruitment modules UDM1 and UDM2. Here the authors combine crystallography, cell biology and biochemical experiments to reveal how UDM1 and UDM2 interact with polyubiquitin chains.

12 January 2018 | doi: 10.1038/s41467-017-02345-y
DNA damage response  Ubiquitylation  X-ray crystallography 

Recent enhanced high-summer North Atlantic Jet variability emerges from three-century context OPEN
V. Trouet, F. Babst & M. Meko

Long-term records of jet stream variability are needed to place recent mid-latitude extreme weather events into a historical context. Here, using tree-ring records from Europe, the authors reconstruct variability in the latitudinal position of the high-summer North Atlantic Jet since 1725 CE.

12 January 2018 | doi: 10.1038/s41467-017-02699-3
Climate change  Palaeoclimate 

Formation and dynamics of a solar eruptive flux tube OPEN
Satoshi Inoue, Kanya Kusano, Jörg Büchner & Jan Skála

Solar eruptions are large explosions occurring in the solar atmosphere. Here, the authors perform magnetohydrodynamic simulations to unveil the dynamics of a solar eruption, and find that these are dominated by nonlinear processes involving flux tube evolution and reconnection.

12 January 2018 | doi: 10.1038/s41467-017-02616-8
Solar physics 

Strong grain neighbour effects in polycrystals OPEN
Hamidreza Abdolvand, Jonathan Wright & Angus J. Wilkinson

Understanding how individual crystals share load inside a polycrystal is crucial to improve component lifetime, but remains difficult to measure. Here, the authors show that the crystal orientation of a grain and that of its neighbours can surprisingly cause stress relaxation in zirconium and titanium under load.

12 January 2018 | doi: 10.1038/s41467-017-02213-9
Mechanical engineering  Mechanical properties  Metals and alloys 

Free choice shapes normalized value signals in medial orbitofrontal cortex OPEN
Hiroshi Yamada, Kenway Louie, Agnieszka Tymula & Paul W. Glimcher

Neurons in prefrontal areas including the medial orbitofrontal cortex (mOFC) represent the relative reward value of choices. Here the authors report that mOFC neurons implement divisive normalization to encode the relative values of lottery options only when the decision involves free choice.

11 January 2018 | doi: 10.1038/s41467-017-02614-w
Decision  Neural encoding 

Sequential forward and reverse transport of the Na+ Ca2+ exchanger generates Ca2+ oscillations within mitochondria OPEN
Krishna Samanta, Gary R. Mirams & Anant B. Parekh

Mitochondrial Ca2+ homoeostasis is tightly regulated and export of Ca2+ is mediated by an Na+Ca2+ exchanger. Here authors show that in depolarised mitochondria the exchanger initially operates in reverse mode, transporting cytosolic Ca2+ into the matrix before it reverts to its forward mode state.

11 January 2018 | doi: 10.1038/s41467-017-02638-2
Cell signalling  Energy metabolism 

Impact on short-lived climate forcers increases projected warming due to deforestation OPEN

The climate impacts of deforestation due to changes in biogenic volatile organic compound emissions, which act as short-lived climate forcers (SLCFs), are poorly understood. Here the authors show that including the impact SLCFs increases the projected warming associated with idealised deforestation scenarios.

11 January 2018 | doi: 10.1038/s41467-017-02412-4
Atmospheric chemistry  Climate and Earth system modelling  Environmental impact  Forestry 

CUG initiation and frameshifting enable production of dipeptide repeat proteins from ALS/FTD C9ORF72 transcripts OPEN
Ricardos Tabet, Laure Schaeffer, Fernande Freyermuth, Melanie Jambeau, Michael Workman, Chao-Zong Lee, Chun-Chia Lin, Jie Jiang, Karen Jansen-West, Hussein Abou-Hamdan, Laurent Désaubry, Tania Gendron, Leonard Petrucelli, Franck Martin & Clotilde Lagier-Tourenne

Repeat-associated non-AUG (RAN) translation contributes to the pathogenic mechanism of several microsatellite expansion diseases. Here the authors delineate the different steps involved in recruiting the ribosome to initiate G4C2 RAN translation to produce poly-Glycine Alanine, poly-Glycine Proline, and poly-Glycine Arginine repeats.

11 January 2018 | doi: 10.1038/s41467-017-02643-5
Amyotrophic lateral sclerosis  Dementia  Ribosome 

Wet-dry cycles enable the parallel origin of canonical and non-canonical nucleosides by continuous synthesis OPEN
Sidney Becker, Christina Schneider, Hidenori Okamura, Antony Crisp, Tynchtyk Amatov, Milan Dejmek & Thomas Carell

How RNA building blocks have formed on an early Earth by a continuous process is still a mystery awaiting its solution. Here, the authors report that fluctuations of physical parameters like temperature and pH could have been enough to facilitate nucleoside formation from simple starting materials.

11 January 2018 | doi: 10.1038/s41467-017-02639-1
Molecular evolution  Chemical origin of life 

Discovery of superconductivity in quasicrystal OPEN
K. Kamiya, T. Takeuchi, N. Kabeya, N. Wada, T. Ishimasa, A. Ochiai, K. Deguchi, K. Imura & N. K. Sato

Superconductivity is evidenced in crystals and amorphous solids, but remains to be discovered in quasicrystals. Here, Kamiya et al. report the emergence of bulk superconductivity in Al-Zn-Mg quasicrystal at a very low transition temperature about 0.05 K.

11 January 2018 | doi: 10.1038/s41467-017-02667-x
Electronic properties and materials  Superconducting properties and materials 

Magnetically induced transparency of a quantum metamaterial composed of twin flux qubits OPEN
K. V. Shulga, E. Il’ichev, M. V. Fistul, I. S. Besedin, S. Butz, O. V. Astafiev, U. Hübner & A. V. Ustinov

Here, the authors demonstrate an array of superconducting qubits embedded into a microwave transmission line. They show that the transmission through the metamaterial periodically depends on externally applied magnetic field and suppression of the transmission is achieved through field-induced transitions.

11 January 2018 | doi: 10.1038/s41467-017-02608-8
Metamaterials  Qubits  Superconducting devices 

Signaling ammonium across membranes through an ammonium sensor histidine kinase OPEN
Tobias Pflüger, Camila F. Hernández, Philipp Lewe, Fabian Frank, Haydyn Mertens, Dmitri Svergun, Manfred W. Baumstark, Vladimir Y. Lunin, Mike S. M. Jetten & Susana L. A. Andrade

For anammox bacteria, the sensing and uptake of ammonium is essential and specialized proteins, like Ks-Amt5, mediate such processes. Here, authors perform biophysical, biochemical, and structural analysis on Ks-Amt5 and establish a role for this protein as an ammonium-sensing signal transducer.

11 January 2018 | doi: 10.1038/s41467-017-02637-3
Ion transport  Permeation and transport  X-ray crystallography 

The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex structure OPEN
Chris H. Hill, Georgia M. Cook, Samantha J. Spratley, Stuart Fawke, Stephen C. Graham & Janet E. Deane

Lysosomal degradation of sphingolipids requires lipid-binding saposin proteins and hydrolytic enzymes. Here the authors present the crystal structure of the hydrolase β-galactocerebrosidase in complex with saposin SapA and give insights into the glycosphingolipid galactocerebroside degradation mechanism.

11 January 2018 | doi: 10.1038/s41467-017-02361-y
Enzyme mechanisms  Lipids  X-ray crystallography 

MXene molecular sieving membranes for highly efficient gas separation OPEN
Li Ding, Yanying Wei, Libo Li, Tao Zhang, Haihui Wang, Jian Xue, Liang-Xin Ding, Suqing Wang, Jürgen Caro & Yury Gogotsi

Two-dimensional materials show great potential for membrane technologies, but their disordered channels hinder their molecular sieving performance. Here, Wang, Gogotsi and colleagues design a MXene membrane with ordered nanochannels that exhibits an excellent H2/CO2 gas separation performance.

11 January 2018 | doi: 10.1038/s41467-017-02529-6
Chemical engineering  Materials chemistry  Porous materials  Two-dimensional materials 

Impaired autophagy bridges lysosomal storage disease and epithelial dysfunction in the kidney OPEN
Beatrice Paola Festa, Zhiyong Chen, Marine Berquez, Huguette Debaix, Natsuko Tokonami, Jenny Ann Prange, Glenn van de Hoek, Cremonesi Alessio, Andrea Raimondi, Nathalie Nevo, Rachel H. Giles, Olivier Devuyst & Alessandro Luciani

Nephropathic cystinosis is a lysosomal storage disease characterized by proximal tubular cell dysfunction. Here Festa and colleagues show that these lysosomal alterations lead to defective autophagic clearance of mitochondria and increased oxidative stress that, in turn, activates the transcription factor ZONAB leading to impaired cell differentiation.

11 January 2018 | doi: 10.1038/s41467-017-02536-7
Fanconi syndrome  Lysosomes  Macroautophagy  Mechanisms of disease 

Quantum engine efficiency bound beyond the second law of thermodynamics OPEN
Wolfgang Niedenzu, Victor Mukherjee, Arnab Ghosh, Abraham G. Kofman & Gershon Kurizki

Evaluating maximum conversion efficiency from heat to work using non-thermal baths can lead to meaningless results, when based only on the reversibility requirement. Here, the authors solve this problem by identifying the fraction of exchanged energy that necessarily causes a change in entropy.

11 January 2018 | doi: 10.1038/s41467-017-01991-6
Statistical physics, thermodynamics and nonlinear dynamics  Theoretical physics 
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