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Nature Communications -03 January 2018

 
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Role of outer surface probes for regulating ion gating of nanochannels OPEN
Xinchun Li, Tianyou Zhai, Pengcheng Gao, Hongli Cheng, Ruizuo Hou, Xiaoding Lou & Fan Xia

Ion gating in biological channels is commonly controlled by functional elements. Here, the authors elucidate the contribution of outer-surface functional elements on ion gating of biomimetic nanochannels, providing insight into the design of effective nanochannel-based biosensors and electronics.

03 January 2018 | doi: 10.1038/s41467-017-02447-7
Biomimetics  Nanobiotechnology 

The protease GtgE from Salmonella exclusively targets inactive Rab GTPases OPEN
Rudolf Wachtel, Bastian Bräuning, Sophie L. Mader, Felix Ecker, Ville R. I. Kaila, Michael Groll & Aymelt Itzen

The bacterial protease GtgE is involved in the establishment of Salmonellosis. Here the authors provide a structural and biochemical analysis of GtgE that sheds light on the molecular mechanisms of reprogramming infected host cells via site-specific proteolytic cleavage of the vesicular trafficking regulator Rab32.

03 January 2018 | doi: 10.1038/s41467-017-02110-1
Bacterial toxins  GTP-binding protein regulators  Proteases  X-ray crystallography 

Electrically reversible cracks in an intermetallic film controlled by an electric field OPEN
Z. Q. Liu, J. H. Liu, M. D. Biegalski, J.-M. Hu, S. L. Shang, Y. Ji, J. M. Wang, S. L. Hsu, A. T. Wong, M. J. Cordill, B. Gludovatz, C. Marker, H. Yan, Z. X. Feng, L. You, M. W. Lin, T. Z. Ward, Z. K. Liu, C. B. Jiang, L. Q. Chen et al.

Electric-field-induced cracks are generally detrimental to functionality of ferroelectric ceramics. Liu et al. use an intermetallic alloy and ferroelectric oxide junction to mediate the reversible formation of cracks at nanoscales, resulting in colossal electroresistance modulation for memory applications.

03 January 2018 | doi: 10.1038/s41467-017-02454-8
Electronic devices  Information storage 

Transient rotation of photospheric vector magnetic fields associated with a solar flare OPEN
Yan Xu, Wenda Cao, Kwangsu Ahn, Ju Jing, Chang Liu, Jongchul Chae, Nengyi Huang, Na Deng, Dale E. Gary & Haimin Wang

The violent solar eruptions known as flares are caused by magnetic reconnection. Here, the authors identify a sudden 12°–20° counter clockwise rotation of vector magnetic fields in photosphere, associated with the emissions of moving flare ribbons.

03 January 2018 | doi: 10.1038/s41467-017-02509-w
Solar physics 

Defects controlled hole doping and multivalley transport in SnSe single crystals OPEN
Zhen Wang, Congcong Fan, Zhixuan Shen, Chenqiang Hua, Qifeng Hu, Feng Sheng, Yunhao Lu, Hanyan Fang, Zhizhan Qiu, Jiong Lu, Zhengtai Liu, Wanling Liu, Yaobo Huang, Zhu-An Xu, D. W. Shen & Yi Zheng

Knowledge of the electronic structure of group-IV monochalcogenides is essential for their application in high-performance thermoelectric energy harvesting. Here, using photoemission spectroscopy, the authors reveal the impact of doping, and the anisotropic nature of the band structure of SnSe.

03 January 2018 | doi: 10.1038/s41467-017-02566-1
Electronic properties and materials  Thermoelectric devices and materials 

Replication-dependent size reduction precedes differentiation in Chlamydia trachomatis  OPEN
Jennifer K. Lee, Germán A. Enciso, Daniela Boassa, Christopher N. Chander, Tracy H. Lou, Sean S. Pairawan, Melody C. Guo, Frederic Y. M. Wan, Mark H. Ellisman, Christine Sütterlin & Ming Tan

The vegetative forms of chlamydiae (RBs) replicate within infected cells and then convert into infectious forms (EBs). Here, the authors use quantitative 3D electron microscopy and computer modeling to show that RB size decreases with replication, and conversion into EBs correlates with an RB size threshold.

03 January 2018 | doi: 10.1038/s41467-017-02432-0
Bacteriology  Cell biology  Cellular microbiology  Pathogens 

A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia OPEN
Su-In Lee, Safiye Celik, Benjamin A. Logsdon, Scott M. Lundberg, Timothy J. Martins, Vivian G. Oehler, Elihu H. Estey, Chris P. Miller, Sylvia Chien, Jin Dai, Akanksha Saxena, C. Anthony Blau & Pamela S. Becker

Identification of markers of drug response is essential for precision therapy. Here the authors introduce an algorithm that uses prior information about each gene’s importance in AML to identify the most predictive gene-drug associations from transcriptome and drug response data from 30 AML samples.

03 January 2018 | doi: 10.1038/s41467-017-02465-5
Acute myeloid leukaemia  Cancer genomics  Machine learning  Molecular medicine 

Antiferromagnetic correlations in the metallic strongly correlated transition metal oxide LaNiO3  OPEN
H. Guo, Z. W. Li, L. Zhao, Z. Hu, C. F. Chang, C.-Y. Kuo, W. Schmidt, A. Piovano, T. W. Pi, O. Sobolev, D. I. Khomskii, L. H. Tjeng & A. C. Komarek

The phase transitions of rare earth nickelates have attracted intensive study as they arise from the complex interplay of charge, spin and lattice degrees of freedom. Here Guo et al. present evidence that LaNiO3 has an unanticipated magnetically ordered metallic phase.

03 January 2018 | doi: 10.1038/s41467-017-02524-x
Electronic properties and materials  Magnetic properties and materials  Solid-state chemistry 

Redox regulation of PEP activity during seedling establishment in Arabidopsis thaliana  OPEN
Manuel Guinea Díaz, Tamara Hernández-Verdeja, Dmitry Kremnev, Tim Crawford, Carole Dubreuil & Åsa Strand

The plastid-encoded RNA polymerase PEP is regulated according to plastid redox state. Here, the authors show that the redox-regulated PRIN2 protein is reduced to monomeric form in a thiol-dependent manner in response to light and that PRIN2 monomers are required for PEP activity and retrograde signaling.

03 January 2018 | doi: 10.1038/s41467-017-02468-2
Chloroplasts  Light responses  Plant molecular biology 

Abrupt transitions in time series with uncertainties OPEN
Bedartha Goswami, Niklas Boers, Aljoscha Rheinwalt, Norbert Marwan, Jobst Heitzig, Sebastian F. M. Breitenbach & Jürgen Kurths

Most time series techniques tend to ignore data uncertainties, which results in inaccurate conclusions. Here, Goswami et al. represent time series as a sequence of probability density functions, and reliably detect abrupt transitions by identifying communities in probabilistic recurrence networks.

03 January 2018 | doi: 10.1038/s41467-017-02456-6
Applied mathematics  Complex networks  Statistics 

Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity OPEN
Yuan Zhang, Na Li, Heikyung Suh & Darrell J. Irvine

Immunostimulatory agents used in cancer treatment often elicit serious toxicities, limiting their clinical application. Here, the authors show that the use of liposomes to intravenously deliver surface-anchored IL-2 and anti-CD137 proteins enables anti-cancer immunity and reduces the toxic side effects.

02 January 2018 | doi: 10.1038/s41467-017-02251-3
Cancer immunotherapy  Immunotherapy  Translational research 

Capacity estimation and verification of quantum channels with arbitrarily correlated errors OPEN
Corsin Pfister, M. Adriaan Rol, Atul Mantri, Marco Tomamichel & Stephanie Wehner

Estimating the quantum capacity allows one to assess the performance of quantum memories, communication channels, repeaters as well as error correction schemes. Here, the authors show how to estimate and verify one-shot quantum capacity in the most general case of arbitrarily correlated errors.

02 January 2018 | doi: 10.1038/s41467-017-00961-2
Information theory and computation  Quantum information  Qubits 

Development of a genetically encodable FRET system using fluorescent RNA aptamers OPEN
Mette D. E. Jepsen, Steffen M. Sparvath, Thorbjørn B. Nielsen, Ane H. Langvad, Guido Grossi, Kurt V. Gothelf & Ebbe S. Andersen

FRET has been used to study protein conformational changes but has never been applied to RNA aptamers. Here the authors develop a genetically encodable RNA aptamer-based FRET system on single-stranded RNA origami scaffolds, and demonstrate it can be used to study RNA conformational changes.

02 January 2018 | doi: 10.1038/s41467-017-02435-x
Biosensors  Nanostructures  RNA nanotechnology 

Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics OPEN
David C. Earl, P. Brent Ferrell Jr, Nalin Leelatian, Jordan T. Froese, Benjamin J. Reisman, Jonathan M. Irish & Brian O. Bachmann

Bioactive metabolites from plant and microbial extracts hold therapeutic potential. Here, the authors combine untargeted metabolomic arrays with flow cytometry-based single cell response profiling and identify metabolites with cell subset-specific activities in the bone marrow from an AML patient.

02 January 2018 | doi: 10.1038/s41467-017-02470-8
Bioanalytical chemistry  Cancer therapy  Metabolomics  Natural products 

Extreme haplotype variation in the desiccation-tolerant clubmoss Selaginella lepidophylla  OPEN
Robert VanBuren, Ching Man Wai, Shujun Ou, Jeremy Pardo, Doug Bryant, Ning Jiang, Todd C. Mockler, Patrick Edger & Todd P. Michael

Selaginella lepidophylla is a clubmoss with extreme desiccation tolerance. Here, the authors assemble its highly heterozygotic haplotypes and examine gene expression changes during desiccation, which shed light on the mechanisms for maintaining a small genome size and adaptation to extreme drying.

02 January 2018 | doi: 10.1038/s41467-017-02546-5
Comparative genomics  DNA sequencing  Drought  Plant evolution 

TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis OPEN
Curdin Conrad, Jeremy Di Domizio, Alessio Mylonas, Cyrine Belkhodja, Olivier Demaria, Alexander A. Navarini, Anne-Karine Lapointe, Lars E. French, Maxime Vernez & Michel Gilliet

The pathogenesis of paradoxical psoriasis in patients receiving anti-TNF treatments for classical psoriasis is unclear. Here, the authors show that anti-TNF drugs enhance the production of type I interferon by plasmacytoid dendritic cells, causing skin lesions that, unlike classical psoriasis, lack T- cell autoimmunity.

02 January 2018 | doi: 10.1038/s41467-017-02466-4
Inflammatory diseases  Interferons  Plasmacytoid dendritic cells  Tumour-necrosis factors 

Non-canonical Wnt signaling regulates neural stem cell quiescence during homeostasis and after demyelination OPEN
Manideep Chavali, Michael Klingener, Alexandros G. Kokkosis, Yury Garkun, Sylwia Felong, Arianna Maffei & Adan Aguirre

Following demyelination injury, neural stem cells (NSCs) in the subventricular zone switch to an activated state. Here, the authors show that a transient shift from non-canonical to canonical Wnt signaling is necessary for activation of quiescent NSCs to achieve tissue homeostasis and brain repair.

02 January 2018 | doi: 10.1038/s41467-017-02440-0
Multiple sclerosis  Neural stem cells  Quiescence 

RAD54 N-terminal domain is a DNA sensor that couples ATP hydrolysis with branch migration of Holliday junctions OPEN
Nadish Goyal, Matthew J. Rossi, Olga M. Mazina, Yong Chi, Robert L. Moritz, Bruce E. Clurman & Alexander V. Mazin

RAD54 stimulates activity of the RAD51 recombinase and catalyzes branch migration of Holliday junctions during DNA repair and recombination. Here the authors show that the N-terminal domain of RAD54 mediates RAD54 oligomerization to promote branch migration, and is the target of phosphorylation that inhibits oligomerization and branch migration but not RAD51 stimulation.

02 January 2018 | doi: 10.1038/s41467-017-02497-x
DNA  DNA recombination  Phosphoproteins 

Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution OPEN
Mirjana Efremova, Dietmar Rieder, Victoria Klepsch, Pornpimol Charoentong, Francesca Finotello, Hubert Hackl, Natascha Hermann-Kleiter, Martin Löwer, Gottfried Baier, Anne Krogsdam & Zlatko Trajanoski

The cancer immunoediting hypothesis assumes the immune system sculpts the cancer genome. Here the authors show, in a mouse model, that neutral evolution outweighs the effects of immunoselection and that immune checkpoint blockade potentiates the immunoediting, switching the system to non-neutral evolution.

02 January 2018 | doi: 10.1038/s41467-017-02424-0
Cancer genomics  Computational biology and bioinformatics  Tumour immunology 

Sirt2 facilitates hepatic glucose uptake by deacetylating glucokinase regulatory protein OPEN
Hitoshi Watanabe, Yuka Inaba, Kumi Kimura, Michihiro Matsumoto, Shuichi Kaneko, Masato Kasuga & Hiroshi Inoue

During diabetes, postprandial hyperglycemia is caused by impaired glucose uptake. Here, Watanabe and colleagues show that impaired hepatic glucose uptake during obesity is caused by a reduction in Sirt2 activity, which promotes glucokinase regulatory protein acetylation and its dissociation from glucokinase.

02 January 2018 | doi: 10.1038/s41467-017-02537-6
Metabolic syndrome  Type 2 diabetes 

LncRNA CAIF inhibits autophagy and attenuates myocardial infarction by blocking p53-mediated myocardin transcription OPEN
Cui-Yun Liu, Yu-Hui Zhang, Rui-Bei Li, Lu-Yu Zhou, Tao An, Rong-Cheng Zhang, Mei Zhai, Yan Huang, Kao-Wen Yan, Yan-Han Dong, Murugavel Ponnusamy, Chan Shan, Sheng Xu, Qi Wang, Yan-Hui Zhang, Jian Zhang & Kun Wang

Little is known about the role of long lncRNAs in autophagy. The authors identify lncCAIF, and show that it suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53 -mediated transcription of myocardin.

02 January 2018 | doi: 10.1038/s41467-017-02280-y
Autophagy  Cardiovascular diseases  Non-coding RNAs 

Momentum-resolved observations of the phonon instability driving geometric improper ferroelectricity in yttrium manganite OPEN
Dipanshu Bansal, Jennifer L. Niedziela, Ryan Sinclair, V. Ovidiu Garlea, Douglas L. Abernathy, Songxue Chi, Yang Ren, Haidong Zhou & Olivier Delaire

The improper ferroelectric mechanism of YMnO3 has been difficult to observe directly but is important for understanding its other interesting properties such as multiferroicity. Bansal et al. use neutron scattering and ab initio calculations to show that phonons drive the transition, confirming earlier theories.

02 January 2018 | doi: 10.1038/s41467-017-02309-2
Ferroelectrics and multiferroics  Phase transitions and critical phenomena 

Perturbation-response genes reveal signaling footprints in cancer gene expression OPEN
Michael Schubert, Bertram Klinger, Martina Klünemann, Anja Sieber, Florian Uhlitz, Sascha Sauer, Mathew J. Garnett, Nils Blüthgen & Julio Saez-Rodriguez

Deregulation of signalling is responsible for many cancer phenotypes. Leveraging available perturbation data, here the authors assess large-scale pathway activity patterns based on consensus downstream readout genes, enabling accurate prediction of the effects of mutations and small molecules.

02 January 2018 | doi: 10.1038/s41467-017-02391-6
Predictive medicine  Tumour biomarkers 

Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314 OPEN
Kimbria J. Blake, Pankaj Baral, Tiphaine Voisin, Ashira Lubkin, Felipe Almeida Pinho-Ribeiro, Kelsey L. Adams, David P. Roberson, Yuxin C. Ma, Michael Otto, Clifford J. Woolf, Victor J. Torres & Isaac M. Chiu

Bacterial infection can cause pain but the underlying mechanism is unclear. This study shows pain induced in mice by methicillin-resistant Staphylococcus aureus infection is mediated by bacterial pore-forming toxins, and a sodium channel blocker QX-314 can alleviate infection-associated pain.

02 January 2018 | doi: 10.1038/s41467-017-02448-6
Bacterial toxins  Bacteriology  Infection  Pain  Pathogens 

Structural basis for DNA 3′-end processing by human tyrosyl-DNA phosphodiesterase 1 OPEN
Fiona J. Flett, Emilija Ruksenaite, Lee A. Armstrong, Shipra Bharati, Roberta Carloni, Elizabeth R. Morris, C. Logan Mackay, Heidrun Interthal & Julia M. Richardson

Human tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs covalently trapped topoisomerase 1B-DNA complexes and other lesions, and is a target for anticancer drug development. Here the authors use an integrated structural approach to shed light onto the molecular basis of DNA end-processing by Tdp1.

02 January 2018 | doi: 10.1038/s41467-017-02530-z
DNA  DNA damage and repair  Mass spectrometry  X-ray crystallography 

Coherent organization of electronic correlations as a mechanism to enhance and stabilize high-T C cuprate superconductivity OPEN
Haoxiang Li, Xiaoqing Zhou, Stephen Parham, Theodore J. Reber, Helmuth Berger, Gerald B. Arnold & Daniel S. Dessau

Whether the normal state electronic correlations in cuprates are responsible for superconductivity remains elusive. Here, Li et al. report that such correlations turn into a renormalized coherent state starting well above the superconducting transition, and it leads to a strengthened superconductive pairing.

02 January 2018 | doi: 10.1038/s41467-017-02422-2
Electronic properties and materials  Superconducting properties and materials 

A unifying theory for top-heavy ecosystem structure in the ocean OPEN
C. Brock Woodson, John R. Schramski & Samantha B. Joye

Evidence of inverted trophic pyramids in marine food webs has been enigmatic owing to lack of theoretical support. Here, Woodson et al. use metabolic and size-spectra theory to show that inverted pyramids are possible when food webs have generalist predators and consumers with large body sizes.

02 January 2018 | doi: 10.1038/s41467-017-02450-y
Ecosystem ecology  Marine biology  Theoretical ecology 

Linking soil biology and chemistry in biological soil crust using isolate exometabolomics OPEN
Tami L. Swenson, Ulas Karaoz, Joel M. Swenson, Benjamin P. Bowen & Trent R. Northen

Metagenomic sequencing provides a window into microbial community structure and metabolic potential. Here, Swenson et al. integrate metabolomics and shotgun sequencing to functionally link microbial community structure with environmental chemistry in biological soil crust (biocrust).

02 January 2018 | doi: 10.1038/s41467-017-02356-9
Environmental chemistry  Metabolomics  Microbial ecology  Soil microbiology 

Metabolic rate evolves rapidly and in parallel with the pace of life history OPEN
Sonya K. Auer, Cynthia A. Dick, Neil B. Metcalfe & David N. Reznick

The ‘pace of life’ depends on both metabolic rate and life history traits; however, whether these evolve similarly in response to the environment is not clear. Here, Auer et al. show parallel evolution of metabolic rate and a suite of life history traits in response to predator environment in Trinidadian guppies.

02 January 2018 | doi: 10.1038/s41467-017-02514-z
Animal physiology  Evolutionary ecology  Experimental evolution  Respiration 

Macrophages orchestrate breast cancer early dissemination and metastasis OPEN
Nina Linde, Maria Casanova-Acebes, Maria Soledad Sosa, Arthur Mortha, Adeeb Rahman, Eduardo Farias, Kathryn Harper, Ethan Tardio, Ivan Reyes Torres, Joan Jones, John Condeelis, Miriam Merad & Julio A. Aguirre-Ghiso

Early dissemination of cancer cells has been reported to occur in certain breast cancer models. Here the authors show that intra-epithelial macrophages in the early pre-cancer lesions drive early cancer cell dissemination through Wnt-1 secretion and that such events impact the later development of metastasis.

02 January 2018 | doi: 10.1038/s41467-017-02481-5
Breast cancer  Cancer microenvironment  Metastasis  Tumour immunology 

Circulating exosomes suppress the induction of regulatory T cells via let-7i in multiple sclerosis OPEN
Kimitoshi Kimura, Hirohiko Hohjoh, Masashi Fukuoka, Wakiro Sato, Shinji Oki, Chiharu Tomi, Hiromi Yamaguchi, Takayuki Kondo, Ryosuke Takahashi & Takashi Yamamura

MiRNAs are small RNA molecules that can regulate gene expression. Here the authors show that expression of several exosomal miRNAs are altered in patients with multiple sclerosis, and that let-7i modulates regulatory T cell homeostasis to contribute to pathogenesis.

02 January 2018 | doi: 10.1038/s41467-017-02406-2
Gene regulation in immune cells  Multiple sclerosis  Neuroimmunology 

Amphiphilic nanocarrier-induced modulation of PLK1 and miR-34a leads to improved therapeutic response in pancreatic cancer OPEN
Hadas Gibori, Shay Eliyahu, Adva Krivitsky, Dikla Ben-Shushan, Yana Epshtein, Galia Tiram, Rachel Blau, Paula Ofek, Joo Sang Lee, Eytan Ruppin, Limor Landsman, Iris Barshack, Talia Golan, Emmanuelle Merquiol, Galia Blum & Ronit Satchi-Fainaro

Treatment of pancreatic ductal adenocarcinoma is still challenging and patients survival has only marginally improved in the last decade. Here the authors produce a PGA-based polymeric nanocarrier for the dual delivery of miR-34a-mimic and PLK1-targeting siRNA resulting in killing of pancreatic cancer cells in vivo.

02 January 2018 | doi: 10.1038/s41467-017-02283-9
RNAi therapy  Targeted therapies 

Protein-inspired antibiotics active against vancomycin- and daptomycin-resistant bacteria OPEN
Mark A. T. Blaskovich, Karl A. Hansford, Yujing Gong, Mark S. Butler, Craig Muldoon, Johnny X. Huang, Soumya Ramu, Alberto B. Silva, Mu Cheng, Angela M. Kavanagh, Zyta Ziora, Rajaratnam Premraj, Fredrik Lindahl, Tanya A. Bradford, June C. Lee, Tomislav Karoli, Ruby Pelingon, David J. Edwards, Maite Amado, Alysha G. Elliott et al.

The antibiotic vancomycin inhibits bacterial cell wall synthesis by binding to a membrane-associated precursor. Here, Blaskovich et al. synthesize vancomycin derivatives containing lipophilic peptide moieties that enhance membrane affinity and in vivo activities against glycopeptide-resistant strains.

02 January 2018 | doi: 10.1038/s41467-017-02123-w
Antibiotics  Bacterial infection  Drug discovery and development  Mechanism of action 

ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma OPEN
Shujun Han, Yibo Ren, Wangxiao He, Huadong Liu, Zhe Zhi, Xinliang Zhu, Tielin Yang, Yu Rong, Bohan Ma, Timothy J. Purwin, Zhenlin Ouyang, Caixia Li, Xun Wang, Xueqiang Wang, Huizi Yang, Yan Zheng, Andrew E. Aplin, Jiankang Liu & Yongping Shao

In BRAF mutant melanoma, inhibition of ERK1/2 induces FOXD3 and mediates RAF inhibitor resistance. Here, the authors show that ERK1/2 mediated phosphorylation regulates sumoylation of SOX10 which activates FOXD3, and depletion of SOX10 sensitises BRAF mutant melanoma cells to RAF inhibitors.

02 January 2018 | doi: 10.1038/s41467-017-02354-x
Cancer  Cell signalling 

Extreme sensitivity to ultraviolet light in the fungal pathogen causing white-nose syndrome of bats OPEN
Jonathan M. Palmer, Kevin P. Drees, Jeffrey T. Foster & Daniel L. Lindner

White-nose syndrome, caused by the fungus Pseudogymnoascus destructans, is decimating North American bats. Here, Palmer et al. use comparative genomics to examine the evolutionary history of this pathogen, and show that it has lost a crucial DNA repair enzyme and is extremely sensitive to UV light.

02 January 2018 | doi: 10.1038/s41467-017-02441-z
Fungal biology  Fungal evolution  Fungal genomics  Pathogens 

Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury OPEN
Tuoyi Li, Bing Yu, Zhixin Liu, Jingyuan Li, Mingliang Ma, Yingbao Wang, Mingjiang Zhu, Huiyong Yin, Xiaofeng Wang, Yi Fu, Fang Yu, Xian Wang, Xiaohong Fang, Jinpeng Sun & Wei Kong

High homocysteine plasma levels are associated with cardiovascular diseases. Here, Li and colleagues find that homocysteine aggravates vascular injury by direct binding to the angiotensin II type 1 receptor (AT1R), identifying AT1R inhibition as a potential strategy to counteract the deleterious vascular effects of hyperhomocysteinemia.

02 January 2018 | doi: 10.1038/s41467-017-02401-7
Aneurysm  Extracellular signalling molecules  Hormone receptors 

Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages OPEN
Jinglian Yan, Guodong Tie, Shouying Wang, Amanda Tutto, Natale DeMarco, Lyne Khair, Thomas G. Fazzio & Louis M. Messina

Type 2 diabetes is associated with impaired wound healing, which can lead to limb loss. Here, the authors show that in Type 2 diabetic mouse models, Dnmt1 is upregulated in hematopoietic stem cells, leading to impaired differentiation towards macrophages, reduced macrophage infiltration in the wound and skewed M1/M2 polarization.

02 January 2018 | doi: 10.1038/s41467-017-02425-z
Diabetes complications  DNA methylation  Haematopoietic stem cells  Monocytes and macrophages 

Network connectivity determines cortical thinning in early Parkinson’s disease progression OPEN
Y. Yau, Y. Zeighami, T. E. Baker, K. Larcher, U. Vainik, M. Dadar, V. S. Fonov, P. Hagmann, A. Griffa, B. Mišić, D. L. Collins & A. Dagher

In Parkinson’s disease (PD), neurodegeneration spreads from the brainstem to the cerebral cortex. Here, in a longitudinal study of PD patients, the authors found that cortical thinning followed neural connectivity from a “disease reservoir”.

02 January 2018 | doi: 10.1038/s41467-017-02416-0
Neural circuits  Parkinson's disease 

Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci OPEN
Christopher G. Bell, Fei Gao, Wei Yuan, Leonie Roos, Richard J. Acton, Yudong Xia, Jordana Bell, Kirsten Ward, Massimo Mangino, Pirro G. Hysi, Jun Wang & Timothy D. Spector

Genomic polymorphisms affect the epigenome, which in turn influences how epigenome- and genome-wide analysis are interpreted. Here, the authors characterise allelic differences in DNA methylation driven by obligatory or facilitative genetic effects, which may affect disease-related loci.

02 January 2018 | doi: 10.1038/s41467-017-01586-1
Epigenomics  Genetics research 

Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5 OPEN
Amanda J Scopelliti, Josep Font, Robert J Vandenberg, Olga Boudker & Renae M Ryan

Cancer cells are reliant on nutrients such as glutamine, which enter the cell via the alanine/serine/cysteine transporter 2 (ASCT2). Here, authors use crystallography to show which amino-acid residues in the substrate-binding site are responsible for conferring glutamine selectivity to ASCT2.

02 January 2018 | doi: 10.1038/s41467-017-02444-w
Cancer metabolism  Permeation and transport  X-ray crystallography 

Inhibition of Poly(A)-binding protein with a synthetic RNA mimic reduces pain sensitization in mice OPEN
Paulino Barragán-Iglesias, Tzu-Fang Lou, Vandita D. Bhat, Salim Megat, Michael D. Burton, Theodore J. Price & Zachary T. Campbell

Poly(A)-binding protein (PABP) is an RNA binding protein with translation function. Here, Barragán-Iglesias and colleagues devise an RNA mimic that inhibits PABP activity, and show that inhibitors can reduce animal’s pain response in vivo when injected locally.

02 January 2018 | doi: 10.1038/s41467-017-02449-5
Ribosome  Sensory processing 

VAMPnets for deep learning of molecular kinetics OPEN
Andreas Mardt, Luca Pasquali, Hao Wu & Frank Noé

Extracting kinetic models from high-throughput molecular dynamics (MD) simulations is laborious and prone to human error. Here the authors introduce a deep learning framework that automates construction of Markov state models from MD simulation data.

02 January 2018 | doi: 10.1038/s41467-017-02388-1
Machine learning  Molecular modelling  Theoretical chemistry 

Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FcεRI interaction OPEN
Frederic Jabs, Melanie Plum, Nick S. Laursen, Rasmus K. Jensen, Brian Mølgaard, Michaela Miehe, Marco Mandolesi, Michèle M. Rauber, Wolfgang Pfützner, Thilo Jakob, Christian Möbs, Gregers R. Andersen & Edzard Spillner

IgE is linked to allergic diseases and there is a great interest in developing anti-IgE therapeutics. Here the authors characterize the binding of human IgE Fc to a single domain antibody (sdab) and show that the sdab induces a closed conformation, which prevents and disrupts IgE binding to its receptor FcεRI and abrogates allergen mediated activation.

02 January 2018 | doi: 10.1038/s41467-017-02312-7
Allergy  Antibody therapy 

Cooperative interactions between seed-borne bacterial and air-borne fungal pathogens on rice OPEN
Boknam Jung, Jungwook Park, Namgyu Kim, Taiying Li, Soyeon Kim, Laura E. Bartley, Jinnyun Kim, Inyoung Kim, Yoonhee Kang, Kihoon Yun, Younghae Choi, Hyun-Hee Lee, Sungyeon Ji, Kwang Sik Lee, Bo Yeon Kim, Jong Cheol Shon, Won Cheol Kim, Kwang-Hyeon Liu, Dahye Yoon, Suhkman Kim et al.

Interactions between bacteria and fungi are common and contribute to ecosystem processes. Here, Jung et al. show that the interaction between two plant pathogens (a seed-borne bacterium and an air-borne fungus) promotes their own survival and dispersal, as well as disease progression on rice plants.

02 January 2018 | doi: 10.1038/s41467-017-02430-2
Bacterial pathogenesis  Fungal pathogenesis  Microbial ecology  Pathogens 

The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling OPEN
Kerry Tedford, Michael Steiner, Stanislav Koshutin, Karin Richter, Laura Tech, Yannik Eggers, Inga Jansing, Kerstin Schilling, Anja Erika Hauser, Mark Korthals & Klaus-Dieter Fischer

Marginal zone B (MZB) cells shuttle between the marginal zone and lymphoid follicle to capture and present peripheral blood antigens. Here the authors show that shear force, such as blood flow from the sinus around the follicle, is a directional cue that induces MZB migration on ICAM-1, and that S1P signaling inhibits this directional migration.

22 December 2017 | doi: 10.1038/s41467-017-02482-4
Cell migration  Cellular motility  Integrins  Marginal zone B cells 

Timing and pacing of the Late Devonian mass extinction event regulated by eccentricity and obliquity OPEN
David De Vleeschouwer, Anne-Christine Da Silva, Matthias Sinnesael, Daizhao Chen, James E. Day, Michael T. Whalen, Zenghui Guo & Philippe Claeys

Understanding of Late Devonian mass extinction mechanisms is poor due to imprecise stratigraphies. Here, using cyclostratigraphic techniques, the authors present a global orbitally-calibrated chronology and reveal the key role of astronomically-forced Milankovitch climate change.

22 December 2017 | doi: 10.1038/s41467-017-02407-1
Carbon cycle  Geochemistry  Palaeoclimate 

Strain profiling and epidemiology of bacterial species from metagenomic sequencing OPEN
Davide Albanese & Claudio Donati

Microbiota is often a complex mixture of multiple coexisting species and strains with high level of phenotypic and genomic variability. Here, Albanese and Donati develop StrainEst for estimating the number and identity of coexisting strains and their relative abundances in mixed metagenomic samples.

22 December 2017 | doi: 10.1038/s41467-017-02209-5
Computational biology and bioinformatics  Metagenomics 

Type-II Dirac semimetal stabilized by electron-phonon coupling OPEN
Mirko M. Möller, George A. Sawatzky, Marcel Franz & Mona Berciu

How lattice degrees of freedom affect the topological properties of electrons remains rarely explored. Here, Moeller et al. predict non-trivial topological effects in long-lived polaron bands by studying a two-dimensional model stabilized by realistic electron-phonon coupling.

22 December 2017 | doi: 10.1038/s41467-017-02442-y
Electronic properties and materials  Topological insulators 

VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses OPEN
Magalie Martineau, Raul E. Guzman, Christoph Fahlke & Jürgen Klingauf

During neurotransmission synaptic vesicles are filled with glutamate by vesicular glutamate transporters (VGLUTs). Here, authors image intact neurons and show that in synaptic vesicles VGLUT functions as a glutamate/proton exchanger associated with a channel-like chloride conductance.

22 December 2017 | doi: 10.1038/s41467-017-02367-6
Neurotransmitters  Transporters in the nervous system 

Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1 OPEN
Julia Pose-Utrilla, Lucía García-Guerra, Ana Del Puerto, Abraham Martín, Jerónimo Jurado-Arjona, Noelia S. De León-Reyes, Andrea Gamir-Morralla, Álvaro Sebastián Serrano, Mónica García-Gallo, Leonor Kremer, Jens Fielitz, Christofer Ireson, Mª José Pérez-Álvarez, Isidro Ferrer, Félix Hernández, Jesús Ávila, Marina Lasa, Miguel R. Campanero & Teresa Iglesias

Excitotoxicity due to excessive glutamate release causes oxidative stress and neuronal death, and is a feature of many brain diseases. Here the authors show that protein kinase D1 is inactivated by excitotoxicity in a model of stroke and that its activation can be neuroprotective.

22 December 2017 | doi: 10.1038/s41467-017-02322-5
Cell death in the nervous system  Neurodegeneration  Stroke 

Dehydrogenative desaturation-relay via formation of multicenter-stabilized radical intermediates OPEN
Yaping Shang, Xiaoming Jie, Krishna Jonnada, Syeda Nahid Zafar & Weiping Su

Synthesis of valuable polyene molecules under mild conditions and with good functional groups tolerance is of paramount importance. Here, the authors show the versatile copper-catalyzed successive dehydrogenation of a variety of organic substrates affording highly conjugated unsaturated products.

22 December 2017 | doi: 10.1038/s41467-017-02381-8
Homogeneous catalysis  Synthetic chemistry methodology  Reaction mechanisms 

Methylation-regulated decommissioning of multimeric PP2A complexes OPEN
Cheng-Guo Wu, Aiping Zheng, Li Jiang, Michael Rowse, Vitali Stanevich, Hui Chen, Yitong Li, Kenneth A. Satyshur, Benjamin Johnson, Ting-Jia Gu, Zuojia Liu & Yongna Xing

Protein phosphatase 2A (PP2A) forms different holoenzymes but little is known about the disassembly of these important signalling complexes. Here the authors present the crystal structure of PP2A bound to TOR signaling pathway regulator (TIPRL) and give insights into the methylation-dependent disassembly of PP2A holenzymes.

22 December 2017 | doi: 10.1038/s41467-017-02405-3
Chaperones  Enzyme mechanisms  Tumour-suppressor proteins  X-ray crystallography 

TNFα blockade overcomes resistance to anti-PD-1 in experimental melanoma OPEN
Florie Bertrand, Anne Montfort, Elie Marcheteau, Caroline Imbert, Julia Gilhodes, Thomas Filleron, Philippe Rochaix, Nathalie Andrieu-Abadie, Thierry Levade, Nicolas Meyer, Céline Colacios & Bruno Ségui

Most melanoma patients do not respond to anti-PD1 therapy. Here, the authors show that TNFα blockade synergizes with anti-PD-1 by preventing anti-PD-1-induced CD8+ T cell death and TIM-3 expression on such cells.

22 December 2017 | doi: 10.1038/s41467-017-02358-7
Melanoma  Tumour immunology 

The F-box protein FKF1 inhibits dimerization of COP1 in the control of photoperiodic flowering OPEN
Byoung-Doo Lee, Mi Ri Kim, Min-Young Kang, Joon-Yung Cha, Su-Hyun Han, Ganesh M. Nawkar, Yasuhito Sakuraba, Sang Yeol Lee, Takato Imaizumi, C. Robertson McClung, Woe-Yeon Kim & Nam-Chon Paek

CONSTANS promotes flowering under long-day conditions in Arabidopsis but is rapidly degraded in short-day conditions. Here the authors show that the blue-light photoreceptor FKF1 can interact with the E3 ligase COP1 in a light-dependent manner and prevent degradation of CO in long-day conditions.

22 December 2017 | doi: 10.1038/s41467-017-02476-2
Flowering  Light responses 

Small-molecule TFEB pathway agonists that ameliorate metabolic syndrome in mice and extend C. elegans lifespan OPEN

Activation of autophagy, via the transcription factor TFEB, is a promising strategy to treat metabolic diseases. Here, the authors report three novel classes of small molecules that promote TFEB nuclear translocation, and provide evidence for the therapeutic efficacy of these compounds in mice and worms.

22 December 2017 | doi: 10.1038/s41467-017-02332-3
Ageing  Fat metabolism  Macroautophagy  Phenotypic screening 

RNA sequencing provides insights into the evolution of lettuce and the regulation of flavonoid biosynthesis OPEN
Lei Zhang, Wenqing Su, Rong Tao, Weiyi Zhang, Jiongjiong Chen, Peiyao Wu, Chenghuan Yan, Yue Jia, Robert M. Larkin, Dean Lavelle, Maria-Jose Truco, Sebastian Reyes Chin-Wo, Richard W. Michelmore & Hanhui Kuang

Horticultural lettuce varieties vary considerably in phenotype. Here, via RNA-seq of 240 different lettuce accessions, the authors identify loci and expression patterns associated with flavonoid and anthocyanin content and show that cultivated lettuce likely arose via a single domestication event.

22 December 2017 | doi: 10.1038/s41467-017-02445-9
Agricultural genetics  Comparative genomics  Genetic variation  Plant domestication 

Reading and editing the Pleurodeles waltl genome reveals novel features of tetrapod regeneration OPEN
Ahmed Elewa, Heng Wang, Carlos Talavera-López, Alberto Joven, Gonçalo Brito, Anoop Kumar, L. Shahul Hameed, May Penrad-Mobayed, Zeyu Yao, Neda Zamani, Yamen Abbas, Ilgar Abdullayev, Rickard Sandberg, Manfred Grabherr, Björn Andersson & András Simon

The Iberian ribbed newt Pleurodeles waltl has a wide spectrum of regeneration abilities. Here, Elewa et al. sequence its ~20 Gb genome and transcriptome to investigate the molecular features underlying its regenerative capacities.

22 December 2017 | doi: 10.1038/s41467-017-01964-9
Genome  Next-generation sequencing  Regeneration  Reprogramming 

Molecular understanding of polyelectrolyte binders that actively regulate ion transport in sulfur cathodes OPEN
Longjun Li, Tod A. Pascal, Justin G. Connell, Frank Y. Fan, Stephen M. Meckler, Lin Ma, Yet-Ming Chiang, David Prendergast & Brett A. Helms

Polymer binders in battery electrodes can affect their performance, however design rules are still lacking. Here, the authors reveal why polyelectrolyte binders outperform charge-neutral alternatives in lithium–sulfur batteries, showing how cationic polyelectrolytes can regulate ion transport selectively.

22 December 2017 | doi: 10.1038/s41467-017-02410-6
Batteries  Polymer characterization 

Access to stereodefined (Z)-allylsilanes and (Z)-allylic alcohols via cobalt-catalyzed regioselective hydrosilylation of allenes OPEN
Chao Wang, Wei Jie Teo & Shaozhong Ge

Controlling selectivity in the hydrosilylation of allenes poses serious challenges in terms of product stereochemistry. Here the authors show that the title reaction proceeds with excellent (Z)-selectivity by use of a cobalt catalyst in the presence of phosphine-based ligands.

22 December 2017 | doi: 10.1038/s41467-017-02382-7
Catalytic mechanisms  Homogeneous catalysis  Synthetic chemistry methodology  Organometallic chemistry 

Near-field spectroscopic investigation of dual-band heavy fermion metamaterials OPEN
Stephanie N. Gilbert Corder, Xinzhong Chen, Shaoqing Zhang, Fengrui Hu, Jiawei Zhang, Yilong Luan, Jack A. Logan, Thomas Ciavatti, Hans A. Bechtel, Michael C. Martin, Meigan Aronson, Hiroyuki S. Suzuki, Shin-ichi Kimura, Takuya Iizuka, Zhe Fei, Keiichiro Imura, Noriaki K. Sato, Tiger H. Tao & Mengkun Liu

Understanding the electromagnetic responses at subwavelength scales is important for achieving tunability. Using a combination of the near-field and far-field spectroscopy, the authors demonstrate a heavy fermion metamaterial with tunable dual-band optical responses by selectively and separately modifying the 4f and 5d band electrons.

22 December 2017 | doi: 10.1038/s41467-017-02378-3
Applied optics  Metamaterials  Phase transitions and critical phenomena 

Structure of a Wbl protein and implications for NO sensing by M. tuberculosis  OPEN
Bassam K. Kudhair, Andrea M. Hounslow, Matthew D. Rolfe, Jason C. Crack, Debbie M. Hunt, Roger S. Buxton, Laura J. Smith, Nick E. Le Brun, Michael P. Williamson & Jeffrey Green

Mycobacterium tuberculosis WhiB1 is a DNA-binding protein with a NO sensitive [4Fe-4S] cluster. Here the authors present the NMR structure of WhiB1 and suggest how loss of the iron-sulfur cluster through nitrosylation affects WhiB1 DNA binding and leads to transcriptional reprogramming.

22 December 2017 | doi: 10.1038/s41467-017-02418-y
Metalloproteins  Pathogens  Solution-state NMR  Transcription factors 

Chromatin state changes during neural development revealed by in vivo cell-type specific profiling OPEN
Owen J. Marshall & Andrea H. Brand

While transitions between active and repressive chromatin states are essential for differentiation, little is known regarding their role during development of the brain in Drosophila. Here, the authors investigate the large scale chromatin remodelling taking place during fly neural development.

22 December 2017 | doi: 10.1038/s41467-017-02385-4
Chromatin  Epigenetics  Neural stem cells  Stem cells 

Generic wound signals initiate regeneration in missing-tissue contexts OPEN
Suthira Owlarn, Felix Klenner, David Schmidt, Franziska Rabert, Antonio Tomasso, Hanna Reuter, Medhanie A. Mulaw, Sören Moritz, Luca Gentile, Gilbert Weidinger & Kerstin Bartscherer

Some wounds trigger regeneration, while others simply heal but how this is regulated is unclear. Here, by manipulating ERK and Wnt signalling pathways, the authors create headless planarians and finless zebrafish and show that wounds that normally only trigger wound healing can activate regeneration of heads and bones.

22 December 2017 | doi: 10.1038/s41467-017-02338-x
Experimental organisms  Morphogenesis 

Protein conformational flexibility modulates kinetics and thermodynamics of drug binding OPEN
M. Amaral, D. B. Kokh, J. Bomke, A. Wegener, H. P. Buchstaller, H. M. Eggenweiler, P. Matias, C. Sirrenberg, R. C. Wade & M. Frech

An understanding of the dynamics of drug binding and unbinding processes is important for drug discovery. Here, the authors give insights into the binding mechanism of small drug-like molecules to human Hsp90 by combining thermodynamics and kinetics studies as well as molecular dynamics simulations.

22 December 2017 | doi: 10.1038/s41467-017-02258-w
Computational biophysics  Enzyme mechanisms  Kinetics  Thermodynamics 

Extracellular ATP elicits DORN1-mediated RBOHD phosphorylation to regulate stomatal aperture OPEN
Dongqin Chen, Yangrong Cao, Hong Li, Daewon Kim, Nagib Ahsan, Jay Thelen & Gary Stacey

Extracellular ATP acts as a damage-associated molecular pattern that triggers signaling responses to wounding and environmental stimuli in plants. Here Chen et al. show that ATP perception by DORN1 can trigger stomatal closure mediated via RBOHD phosphorylation and ROS production.

22 December 2017 | doi: 10.1038/s41467-017-02340-3
Effectors in plant pathology  Pattern recognition receptors in plants  Plant signalling  Stomata 

Diurnal cloud cycle biases in climate models OPEN
Jun Yin & Amilcare Porporato

The timing of clouds is critical to the Earth’s energy balance. Here the authors show that in current climate models, clouds over the land tend to peak too early in the morning, reflecting less solar radiation than observed.

22 December 2017 | doi: 10.1038/s41467-017-02369-4
Atmospheric dynamics  Climate and Earth system modelling  Projection and prediction 

Pre-critical fluctuations and what they disclose about heterogeneous crystal nucleation OPEN
Martin Fitzner, Gabriele C. Sosso, Fabio Pietrucci, Silvio Pipolo & Angelos Michaelides

Heterogeneous nucleation is a process that mediates the birth of many crystalline materials, but is not fully understood. Here, the authors show that the study of precritical cluster fluctuations paves new ways for the identification of polymorphism, polymorphic control and theoretical modeling.

22 December 2017 | doi: 10.1038/s41467-017-02300-x
Chemical physics  Molecular dynamics  Phase transitions and critical phenomena 

Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid OPEN
Youngzee Song, Huihao Zhou, My-Nuong Vo, Yi Shi, Mir Hussain Nawaz, Oscar Vargas-Rodriguez, Jolene K. Diedrich, John R. Yates, Shuji Kishi, Karin Musier-Forsyth & Paul Schimmel

Non-proteinogenic (np) amino acids in the food chain present challenges for the human translation machinery. Here the authors show that, while AlaRS and ProRS activate toxic np azetidine-2-carboxylic acid (Aze) present in sugar beets and lilies, only the AlaRS editing system rejects Aze.

22 December 2017 | doi: 10.1038/s41467-017-02201-z
Enzyme mechanisms  Proteins  tRNAs  X-ray crystallography 

Quantum Hall states observed in thin films of Dirac semimetal Cd3As2  OPEN
Masaki Uchida, Yusuke Nakazawa, Shinichi Nishihaya, Kazuto Akiba, Markus Kriener, Yusuke Kozuka, Atsushi Miyake, Yasujiro Taguchi, Masashi Tokunaga, Naoto Nagaosa, Yoshinori Tokura & Masashi Kawasaki

Despite many achievements in the topological semimetal Cd3As2, the high-quality Cd3As2 films are still rare. Here, Uchida et al. grow high-crystallinity and high-mobility Cd3As2 thin films and observe quantum Hall states dependent on the confinement thickness.

22 December 2017 | doi: 10.1038/s41467-017-02423-1
Electronic properties and materials  Surfaces, interfaces and thin films  Topological insulators 

Rainbow peacock spiders inspire miniature super-iridescent optics OPEN
Bor-Kai Hsiung, Radwanul Hasan Siddique, Doekele G. Stavenga, Jürgen C. Otto, Michael C. Allen, Ying Liu, Yong-Feng Lu, Dimitri D. Deheyn, Matthew D. Shawkey & Todd A. Blackledge

Several animals and plants get their often spectacular colouration and iridescence from structural colouration. Here, Hsiung et al. show the 3-dimensional nanostructures that produce the rainbow colours on the abdomen of miniature peacock spiders.

22 December 2017 | doi: 10.1038/s41467-017-02451-x
Biophotonics  Nanophotonics and plasmonics 

Imaging the square of the correlated two-electron wave function of a hydrogen molecule OPEN
M. Waitz, R. Y. Bello, D. Metz, J. Lower, F. Trinter, C. Schober, M. Keiling, U. Lenz, M. Pitzer, K. Mertens, M. Martins, J. Viefhaus, S. Klumpp, T. Weber, L. Ph. H. Schmidt, J. B. Williams, M. S. Schöffler, V. V. Serov, A. S. Kheifets, L. Argenti et al.

Electron-electron correlation is a complex and interesting phenomenon that occurs in multi-electron systems. Here, the authors demonstrate the imaging of the correlated two-electron wave function in hydrogen molecule using the coincident detection of the electron and proton after the photoionization.

22 December 2017 | doi: 10.1038/s41467-017-02437-9
Atomic and molecular interactions with photons  Chemical physics  Electronic structure of atoms and molecules  Techniques and instrumentation 

Antimicrobial peptide capsids of de novo design OPEN
Emiliana De Santis, Hasan Alkassem, Baptiste Lamarre, Nilofar Faruqui, Angelo Bella, James E. Noble, Nicola Micale, Santanu Ray, Jonathan R. Burns, Alexander R. Yon, Bart W. Hoogenboom & Maxim G. Ryadnov

With the growing threat of antibiotic resistance, unconventional approaches to antimicrobial discovery are needed. Here, the authors present a peptide topology that mimics virus architecture and assembles into antimicrobial capsids that disrupt bacterial membranes upon contact.

22 December 2017 | doi: 10.1038/s41467-017-02475-3
Antimicrobials  Protein design  Self-assembly 

Large bipolaron density at organic semiconductor/electrode interfaces OPEN
Rijul Dhanker, Christopher L. Gray, Sukrit Mukhopadhyay, Sean Nunez, Chiao-Yu Cheng, Anatoliy N. Sokolov & Noel C. Giebink

Bipolarons - two electrons or holes localized on the same molecule - are generally considered negligible in organic electronic devices. Dhanker et al. show that large bipolaron densities can exist near electrode interfaces and that they are linked to the phenomenon of unipolar organic magnetoresistance.

21 December 2017 | doi: 10.1038/s41467-017-02459-3
Electronic devices  Electronic properties and materials 

Catalytic asymmetric synthesis of a nitrogen heterocycle through stereocontrolled direct photoreaction from electronically excited state OPEN
Xiaoqiang Huang, Xinyao Li, Xiulan Xie, Klaus Harms, Radostan Riedel & Eric Meggers

Despite intensive research on photoexcited molecules, stereocontrol of direct bond formation upon photoexcitation remains limited. Here the authors expand the research on stereocontrolled bond forming photochemistry and introduce the catalytic asymmetric synthesis of chiral nitrogen heterocycles.

21 December 2017 | doi: 10.1038/s41467-017-02148-1
Asymmetric synthesis  Synthetic chemistry methodology  Photocatalysis 

Solving for ambiguities in radar geophysical exploration of planetary bodies by mimicking bats echolocation OPEN
Leonardo Carrer & Lorenzo Bruzzone

Radar sounders, used for the geophysical exploration of celestial objects in the solar system, possess striking similarities to bat sonars. Here, the authors adapt and implement the bat clutter mitigation mechanism to radar geophysical exploration of planetary bodies.

21 December 2017 | doi: 10.1038/s41467-017-02334-1
Electrical and electronic engineering  Planetary science 

Long-lived efficient delayed fluorescence organic light-emitting diodes using n-type hosts OPEN
Lin-Song Cui, Shi-Bin Ruan, Fatima Bencheikh, Ryo Nagata, Lei Zhang, Ko Inada, Hajime Nakanotani, Liang-Sheng Liao & Chihaya Adachi

OLEDs based on thermally activated delayed fluorescence have shown high fluorescence efficiency but poor lifetime. Herein, Cui et al. demonstrate that the use of n-type host molecules can increase the device lifetime by 30 times and 1000 times for green and blue OLEDs, respectively.

21 December 2017 | doi: 10.1038/s41467-017-02419-x
Electronic devices  Organic LEDs 

The podoplanin-CLEC-2 axis inhibits inflammation in sepsis OPEN
Julie Rayes, Siân Lax, Surasak Wichaiyo, Stephanie K. Watson, Ying Di, Stephanie Lombard, Beata Grygielska, Stuart W. Smith, Kassiani Skordilis & Steve P. Watson

Sepsis is a life-threatening condition where exaggerated inflammatory responses lead to severe tissue damage. Here, Rayes and colleagues show that the interaction between podoplanin and its receptor CLEC-2 on platelets plays a critical role in limiting inflammation during sepsis.

21 December 2017 | doi: 10.1038/s41467-017-02402-6
Monocytes and macrophages  Platelets  Sepsis 

Promoter-enhancer interactions identified from Hi-C data using probabilistic models and hierarchical topological domains OPEN
Gil Ron, Yuval Globerson, Dror Moran & Tommy Kaplan

Proximity-ligation methods like Hi-C map DNA-DNA interactions and reveal its organization into topologically associating domains (TADs). Here the authors describe PSYCHIC, a computational approach for analysing Hi-C data that allows the identification of promoter-enhancer interactions.

21 December 2017 | doi: 10.1038/s41467-017-02386-3
Chromatin  Computational biology and bioinformatics  Genome informatics 

The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis OPEN
Han Feng, Xuehui Liu, Sheng Wang, Joy Fleming, Da-Cheng Wang & Wei Liu

New Delhi metallo-β-lactamases (NDMs) hydrolyze almost all β-lactam antibiotics and pose a major public health threat. Here, the authors study the mechanism of NDM-1 catalyzed carbapenem hydrolysis and present the crystal structures of the enzyme-intermediate and product complexes, which is important for drug design.

21 December 2017 | doi: 10.1038/s41467-017-02339-w
Enzyme mechanisms  NMR spectroscopy  X-ray crystallography 

A conserved ankyrin repeat-containing protein regulates conoid stability, motility and cell invasion in Toxoplasma gondii  OPEN
Shaojun Long, Bryan Anthony, Lisa L. Drewry & L. David Sibley

Apicomplexan parasites such as Toxoplasma gondii possess a tubulin-rich structure called the conoid. Here, Long et al. identify a conoid protein that interacts with motor and structural proteins and is required for structural integrity of the conoid, parasite motility, and host cell invasion.

21 December 2017 | doi: 10.1038/s41467-017-02341-2
Microtubules  Parasite biology 

Cryo-EM structure of a licensed DNA replication origin OPEN
Ferdos Abid Ali, Max E. Douglas, Julia Locke, Valerie E. Pye, Andrea Nans, John F. X. Diffley & Alessandro Costa

Origins of replication are licensed by loading of MCM onto DNA, and origin firing depends on interaction with Cdc45 and GINS to form two CMG holo-helicases. Here, authors determine the cryo-EM structures of DNA-bound MCM and visualise a phospho-dependent MCM element important for Cdc45 recruitment.

21 December 2017 | doi: 10.1038/s41467-017-02389-0
Cryoelectron microscopy  DNA  Holoenzymes 

Transmission of heat modes across a potential barrier OPEN
Amir Rosenblatt, Fabien Lafont, Ivan Levkivskyi, Ron Sabo, Itamar Gurman, Daniel Banitt, Moty Heiblum & Vladimir Umansky

Understanding the transfer of heat currents, specifically, neutral heat modes which do not carry net charge, is of great interest. Here, the authors study the transmission of upstream neutral modes through a quantum point contact in order to render the relative spatial distribution of these chargeless modes.

21 December 2017 | doi: 10.1038/s41467-017-02433-z
Electronic devices  Quantum Hall 

Circadian clock regulates hepatic polyploidy by modulating Mkp1-Erk1/2 signaling pathway OPEN
Hsu-Wen Chao, Masao Doi, Jean-Michel Fustin, Huatao Chen, Kimihiko Murase, Yuki Maeda, Hida Hayashi, Rina Tanaka, Maho Sugawa, Naoki Mizukuchi, Yoshiaki Yamaguchi, Jun-ichirou Yasunaga, Masao Matsuoka, Mashito Sakai, Michihiro Matsumoto, Shinshichi Hamada & Hitoshi Okamura

Circadian clock regulates hepatic gene expression and functions. Here Chao et al. show that alteration of circadian clock genes by Period deletion induces polyploidy in hepatocytes due to impaired regulation of Erk signaling by mitogen-activated protein kinase phosphatase 1.

21 December 2017 | doi: 10.1038/s41467-017-02207-7
Circadian rhythms  Cytokinesis 

Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4–MD2 complex OPEN

Reactive species of oxygen promote the development of hepatic steatosis. Here, Kim et al. demonstrate that palmitate stimulates macrophage infiltration and increases oxidative stress during steatosis by binding to the TLR4–MD2 complex, which results in the activation of NOX2.

21 December 2017 | doi: 10.1038/s41467-017-02325-2
Kupffer cells  Non-alcoholic steatohepatitis  Toll-like receptors 

Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1 OPEN
Metehan Cifdaloz, Lisa Osterloh, Osvaldo Graña, Erica Riveiro-Falkenbach, Pilar Ximénez-Embún, Javier Muñoz, Cristina Tejedo, Tonantzin G. Calvo, Panagiotis Karras, David Olmeda, Belén Miñana, Gonzalo Gómez-López, Estela Cañon, Eduardo Eyras, Haihong Guo, Ferdinand Kappes, Pablo L. Ortiz-Romero, Jose L. Rodríguez-Peralto, Diego Megías, Juan Valcárcel et al.

Hundreds of mRNA binding proteins (mRBPs) have been described in mammalian cells. Here, the authors identify RBPs differentially regulated in melanoma, and show the RBP CELF1 controlling a distinct set of protumorigenic factors.

21 December 2017 | doi: 10.1038/s41467-017-02353-y
Cancer  Oncogenes 

Glutaminolysis drives membrane trafficking to promote invasiveness of breast cancer cells OPEN
Emmanuel Dornier, Nicolas Rabas, Louise Mitchell, David Novo, Sandeep Dhayade, Sergi Marco, Gillian Mackay, David Sumpton, Maria Pallares, Colin Nixon, Karen Blyth, Iain R. Macpherson, Elena Rainero & Jim C. Norman

Glutamine metabolism is well known to support tumour growth. Here the authors show that cancer cells also utilize glutamine to promote invasiveness by converting it to glutamate, which upon secretion activates metabotropic glutamate receptors to stimulate matrix metalloproteases recycling to the cell surface.

21 December 2017 | doi: 10.1038/s41467-017-02101-2
Cancer metabolism  Cell invasion  Membrane trafficking 

A molecular basis for water motion detection by the mechanosensory lateral line of zebrafish OPEN
Shih-Wei Chou, Zongwei Chen, Shaoyuan Zhu, Robin W. Davis, Jiaqi Hu, Li Liu, Carol A. Fernando, Kayla Kindig, William C. Brown, Ruben Stepanyan & Brian M. McDermott Jr.

 In fish, water motion is detected by mechanosensitive hair cells located in the lateral line. Here the authors show that the molecular machinery for mechanotransduction, including transmembrane channel-like 2b (Tmc2b), varies depending on both hair cell location and hair bundle orientation.

21 December 2017 | doi: 10.1038/s41467-017-01604-2
Hair cell  Molecular neuroscience  Sensory processing 

Factoring economic costs into conservation planning may not improve agreement over priorities for protection OPEN
Paul R. Armsworth, Heather B. Jackson, Seong-Hoon Cho, Melissa Clark, Joseph E. Fargione, Gwenllian D. Iacona, Taeyoung Kim, Eric R. Larson, Thomas Minney & Nathan A. Sutton

Prioritising areas for conservation is hindered by disagreements over ecological targets. Here, Armsworth et al. combine a simulation approach and case study to test if considering economic return on investment aids in prioritisation, and find that its impact on reaching agreements varies greatly.

21 December 2017 | doi: 10.1038/s41467-017-02399-y
Biodiversity  Conservation biology  Environmental economics  Forestry  Sustainability 

DNA methylation signatures of illicit drug injection and hepatitis C are associated with HIV frailty OPEN
Xinyu Zhang, Ying Hu, Amy C Justice, Boyang Li, Zuoheng Wang, Hongyu Zhao, John H Krystal & Ke Xu

Intravenous illicit drug use (IDU) and hepatitis C infection (HCV) often occur among HIV-infected individuals. Here, the authors report an epigenome-wide association analysis of IDU and HCV in HIV-infected individuals, finding that their associated methylation signatures inform HIV frailty.

21 December 2017 | doi: 10.1038/s41467-017-02326-1
Epigenomics  Molecular medicine 

Coupling ultracold atoms to a superconducting coplanar waveguide resonator OPEN
H. Hattermann, D. Bothner, L. Y. Ley, B. Ferdinand, D. Wiedmaier, L. Sárkány, R. Kleiner, D. Koelle & J. Fortágh

Using ultracold atoms in hybrid quantum devices is an interesting yet challenging task with possible applications for quantum storage. Here the authors demonstrate coherent magnetic coupling of an ensemble of ultracold rubidium atoms to a superconducting coplanar waveguide resonator.

21 December 2017 | doi: 10.1038/s41467-017-02439-7
Atomic and molecular interactions with photons  Ultracold gases 

Decision-making in plants under competition OPEN
Michal Gruntman, Dorothee Groß, Maria Májeková & Katja Tielbörger

Plants may respond to light competition by growing upwards, via physiological changes that maximise performance under low light, or by growing laterally. Here Gruntman et al. show that the light-competition scenario determines the strategy employed by the clonal plant Potentilla reptans.

21 December 2017 | doi: 10.1038/s41467-017-02147-2
Light responses  Plant ecology 

Lipid moieties on lipoproteins of commensal and non-commensal staphylococci induce differential immune responses OPEN
Minh-Thu Nguyen, Julia Uebele, Nimerta Kumari, Hiroshi Nakayama, Lena Peter, Olga Ticha, Anne-Kathrin Woischnig, Mathias Schmaler, Nina Khanna, Naoshi Dohmae, Bok Luel Lee, Isabelle Bekeredjian-Ding & Friedrich Götz

The Lpp lipoproteins of staphylococci trigger a TLR2-dependent immune response. Here, the authors show that commensal species (S. aureus, S. epidermidis) induce a less-intense TLR2 response than non-commensal species (S. carnosus) due to differential modification of the Lpp lipid moieties.

21 December 2017 | doi: 10.1038/s41467-017-02234-4
Bacterial immune evasion  Cellular microbiology  Immune evasion  Toll-like receptors 

Spontaneous and specific chemical cross-linking in live cells to capture and identify protein interactions OPEN
Bing Yang, Shibing Tang, Cheng Ma, Shang-Tong Li, Guang-Can Shao, Bobo Dang, William F. DeGrado, Meng-Qiu Dong, Peng George Wang, Sheng Ding & Lei Wang

Proteins associate via weak and transient interactions that are challenging to identify in vivo. Here, the authors use a genetically encoded chemical cross-linker to covalently lock interacting proteins in live cells, allowing them to identify the captured proteins by mass spectrometry.

21 December 2017 | doi: 10.1038/s41467-017-02409-z
Chemical tools  Proteins 

Mammalian display screening of diverse cystine-dense peptides for difficult to drug targets OPEN
Zachary R. Crook, Gregory P. Sevilla, Della Friend, Mi-Youn Brusniak, Ashok D. Bandaranayake, Midori Clarke, Mesfin Gewe, Andrew J. Mhyre, David Baker, Roland K. Strong, Philip Bradley & James M. Olson

Pathologies related to protein:protein interaction are hard to treat but cystine-dense peptides have the potential to disrupt such interactions. Here the authors develop a high-diversity mammalian cell screen for cystine-dense peptides with drug potential and use it to identify a YAP:TEAD inhibitor.

21 December 2017 | doi: 10.1038/s41467-017-02098-8
Drug development  High-throughput screening  Protein design  Recombinant peptide therapy 
 
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