| Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system OPEN | | Julia Ramírez, Stefan van Duijvenboden, Ioanna Ntalla, Borbala Mifsud, Helen R Warren, Evan Tzanis, Michele Orini, Andrew Tinker, Pier D. Lambiase & Patricia B. Munroe | | Genome-wide association studies have identified multiple loci for resting heart rate (HR) but the genetic factors associated with HR increase during and HR recovery after exercise are less well studied. Here, the authors examine both traits in a two-stage GWAS design in up to 67,257 individuals from UK Biobank. | | 16 May 2018 | doi: 10.1038/s41467-018-04148-1 | | Cardiovascular genetics Genetics of the nervous system Genome-wide association studies Physiology | A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica OPEN | | Karol Estrada, Christopher W. Whelan, Fengmei Zhao, Paola Bronson, Robert E. Handsaker, Chao Sun, John P. Carulli, Tim Harris, Richard M. Ransohoff, Steven A. McCarroll, Aaron G. Day-Williams, Benjamin M. Greenberg & Daniel G. MacArthur | | Neuromyelitis optica (NMO) is a rare autoimmune condition characterized by inflammation and demyelination of the optic nerve and the spinal cord. Here, Estrada et al. identify NMO susceptibility variants in the MHC region and find that autoantibody-positive NMO genetically overlaps with lupus. | | 16 May 2018 | doi: 10.1038/s41467-018-04332-3 | | Autoimmune diseases Demyelinating diseases Genome-wide association studies Neuroimmunology | Hollow organic capsules assemble into cellular semiconductors OPEN | | Boyuan Zhang, Raúl Hernández Sánchez, Yu Zhong, Melissa Ball, Maxwell W. Terban, Daniel Paley, Simon J. L. Billinge, Fay Ng, Michael L. Steigerwald & Colin Nuckolls | | Perylene diimide-bithiophene macrocycles are electroactive and shape-persistent hosts. Here, the authors describe their self-assembly into a cellular organic semiconducting film whose voids are electrically sensitive to different guests, and which can function as the active layer in a field-effect transistor device. | | 16 May 2018 | doi: 10.1038/s41467-018-04246-0 | | Electronic materials Molecular capsules Organic chemistry Self-assembly | Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer OPEN | | Anita Sarkar, Shridhar Bale, Anna-Janina Behrens, Sonu Kumar, Shailendra Kumar Sharma, Natalia de Val, Jesper Pallesen, Adriana Irimia, Devan C. Diwanji, Robyn L. Stanfield, Andrew B. Ward, Max Crispin, Richard T. Wyatt & Ian A. Wilson | | Native-like soluble HIV envelope (Env) trimers are potential vaccine immunogens, and elimination of furin-dependence could provide a DNA-based alternative. Here, Sarkar et al. show that a cleavage-independent Env construct recapitulates the architecture and glycosylation of the native cleaved trimer. | | 16 May 2018 | doi: 10.1038/s41467-018-04272-y | | Glycosylation HIV infections Vaccines X-ray crystallography | Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice OPEN | | Tatyana Grinenko, Anne Eugster, Lars Thielecke, Beáta Ramasz, Anja Krüger, Sevina Dietz, Ingmar Glauche, Alexander Gerbaulet, Malte von Bonin, Onur Basak, Hans Clevers, Triantafyllos Chavakis & Ben Wielockx | | Dependence of hematopoietic stem cell (HSC) fate on the phase of the cell cycle has not been demonstrated in vivo. Here, the authors find that HSCs can differentiate into a downstream progenitor without physical division, even before progressing into the S phase of the cell cycle. | | 15 May 2018 | doi: 10.1038/s41467-018-04188-7 | | Adult stem cells Haematopoietic stem cells Stem-cell differentiation | Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes OPEN | | Rizi Ai, Teresina Laragione, Deepa Hammaker, David L. Boyle, Andre Wildberg, Keisuke Maeshima, Emanuele Palescandolo, Vinod Krishna, David Pocalyko, John W. Whitaker, Yuchen Bai, Sunil Nagpal, Kurtis E. Bachman, Richard I. Ainsworth, Mengchi Wang, Bo Ding, Percio S. Gulko, Wei Wang & Gary S. Firestein | | Fibroblast-like synoviocytes (FLS) in the intimal layer of the synovium can become invasive and destroy cartilage in patients with rheumatoid arthritis (RA). Here the authors integrate a variety of epigenomic data to map the epigenome of FLS in RA and identify potential therapeutic targets. | | 15 May 2018 | doi: 10.1038/s41467-018-04310-9 | | Epigenomics Immunology Rheumatoid arthritis | STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion OPEN | | Jung-Mao Hsu, Weiya Xia, Yi-Hsin Hsu, Li-Chuan Chan, Wen-Hsuan Yu, Jong-Ho Cha, Chun-Te Chen, Hsin-Wei Liao, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L. Hsu, Chia-Wei Li, Seung-Oe Lim, Shih-Shin Chang, Yi-Chun Chen, Guo-xin Ren & Mien-Chie Hung | | PD-L1 accumulates on cancer stem cells and favours immune evasion but the mechanism underlying this accumulation are unknown. Here the authors show that epithelial-mesenchymal transition induces glycosylation and stabilisation of PD-L1; antagonising this process renders cancer cells sensitive to anti-Tim3-therapy. | | 15 May 2018 | doi: 10.1038/s41467-018-04313-6 | | Cancer Glycosylation | Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection OPEN | | Hongshuo Song , Elena E. Giorgi, Vitaly V. Ganusov, Fangping Cai, Gayathri Athreya, Hyejin Yoon, Oana Carja, Bhavna Hora, Peter Hraber, Ethan Romero-Severson, Chunlai Jiang, Xiaojun Li, Shuyi Wang, Hui Li, Jesus F. Salazar-Gonzalez, Maria G. Salazar, Nilu Goonetilleke, Brandon F. Keele, David C. Montefiori, Myron S. Cohen et al. | | Recombination contributes to HIV evolution in patients, but its identification can be difficult. Here, the authors develop a computational tool called RAPR to track recombination in patients, identify recombination hot spots, and show contribution of recombination to antibody escape. | | 15 May 2018 | doi: 10.1038/s41467-018-04217-5 | | Computational platforms and environments Experimental evolution HIV infections Viral genetics | Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate OPEN | | Terytty Yang Li, Lintao Song, Yu Sun, Jingyi Li, Cong Yi, Sin Man Lam, Dijin Xu, Linkang Zhou, Xiaotong Li, Ying Yang, Chen-Song Zhang, Changchuan Xie, Xi Huang, Guanghou Shui, Shu-Yong Lin, Karen Reue & Sheng-Cai Lin | | The acetyltransferase Tip60 mediates signaling pathways by acetylating non-histone proteins. Here the authors show that fatty acids induce Tip60–dependent acetylation of phosphatidic acid phosphatase lipin1 which, then, translocates to the ER and generates diacylglycerols for triglyceride synthesis. | | 15 May 2018 | doi: 10.1038/s41467-018-04363-w | | Acetylation Fat metabolism | Symmetry mismatch-driven perpendicular magnetic anisotropy for perovskite/brownmillerite heterostructures OPEN | | Jing Zhang, Zhicheng Zhong, Xiangxiang Guan, Xi Shen, Jine Zhang, Furong Han, Hui Zhang, Hongrui Zhang, Xi Yan, Qinghua Zhang, Lin Gu, Fengxia Hu, Richeng Yu, Baogen Shen & Jirong Sun | | Complex oxide heterostructures exhibit multifunctional behaviour that could be used in a range of device applications. Here, the authors observe that reconstruction at oxide perovskite/brownmillerite interfaces leads to perpendicular magnetic spin orientation, with potential use in spintronic devices. | | 15 May 2018 | doi: 10.1038/s41467-018-04304-7 | | Applied physics Surfaces, interfaces and thin films | Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages OPEN | | Evelien M. Bunnik, Kate B. Cook, Nelle Varoquaux, Gayani Batugedara, Jacques Prudhomme, Anthony Cort, Lirong Shi, Chiara Andolina, Leila S. Ross, Declan Brady, David A. Fidock, Francois Nosten, Rita Tewari, Photini Sinnis, Ferhat Ay, Jean-Philippe Vert, William Stafford Noble & Karine G. Le Roch | | The development of malaria parasites is controlled by coordinated changes in gene expression. Here, the authors show that the three-dimensional genome structure of human malaria parasites is strongly connected with transcriptional activity of specific gene families throughout the life cycles of Plasmodium falciparum and Plasmodium vivax parasites. | | 15 May 2018 | doi: 10.1038/s41467-018-04295-5 | | Epigenomics Malaria Nuclear organization Parasitology | Coherent X-rays reveal the influence of cage effects on ultrafast water dynamics OPEN | | Fivos Perakis , Gaia Camisasca, Thomas J. Lane, Alexander Späh, Kjartan Thor Wikfeldt, Jonas A. Sellberg, Felix Lehmkühler, Harshad Pathak, Kyung Hwan Kim, Katrin Amann-Winkel, Simon Schreck, Sanghoon Song, Takahiro Sato, Marcin Sikorski, Andre Eilert, Trevor McQueen, Hirohito Ogasawara, Dennis Nordlund, Wojciech Roseker, Jake Koralek et al. | | The dynamics of liquid water is rich due to its complex, highly disordered hydrogen-bond network, which hasn’t been fully understood. Perakis et al. measure water dynamics at sub-100 fs and show that it cannot be described by simple thermal motion due to the build-up of tetrahedral structures upon supercooling. | | 15 May 2018 | doi: 10.1038/s41467-018-04330-5 | | Chemical physics Imaging techniques | Emergent superconductivity in an iron-based honeycomb lattice initiated by pressure-driven spin-crossover OPEN | | Yonggang Wang, Jianjun Ying, Zhengyang Zhou, Junliang Sun, Ting Wen, Yannan Zhou, Nana Li, Qian Zhang, Fei Han, Yuming Xiao, Paul Chow, Wenge Yang, Viktor V. Struzhkin, Yusheng Zhao & Ho-kwang Mao | | Up to now, all iron-based high-Tc superconductors contain a square iron lattice. Here, Wang et al. report the observation of superconductivity in an iron honeycomb lattice accompanied with pressure-driven spin-crossover, in-plane lattice collapse and insulator-metal transition. | | 15 May 2018 | doi: 10.1038/s41467-018-04326-1 | | Superconducting properties and materials Superconductors | PCGF5 is required for neural differentiation of embryonic stem cells OPEN | | Mingze Yao, Xueke Zhou, Jiajian Zhou, Shixin Gong, Gongcheng Hu, Jiao Li, Kaimeng Huang, Ping Lai, Guang Shi, Andrew P. Hutchins, Hao Sun, Huating Wang & Hongjie Yao | | Polycomb-group proteins are key regulators of transcriptional programs that maintain cell identity. Here the authors provide evidence that PCGF5, a subunit of Polycomb Repressor Complex 1, is important for the differentiation of mouse embryonic stem cells towards a neural cell fate. | | 15 May 2018 | doi: 10.1038/s41467-018-03781-0 | | Embryonic stem cells Gene silencing Histone post-translational modifications | Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer OPEN | | Myoung-Hee Kang, Hyunji Choi, Masanobu Oshima, Jae-Ho Cheong, Seokho Kim, Jung Hoon Lee, Young Soo Park, Hueng-Sik Choi, Mi-Na Kweon, Chan-Gi Pack, Ju-Seog Lee, Gordon B. Mills, Seung-Jae Myung & Yun-Yong Park | | Very little is known regarding the molecular mechanisms involved in gastric cancer development. Here the authors show estrogen-related receptor gamma (ESRRG) is a tumor suppressor in gastric cancer and suggest the mechanism of this tumor suppression function involves the inhibition of Wnt signaling. | | 15 May 2018 | doi: 10.1038/s41467-018-04244-2 | | Gastric cancer Transcription Transcriptional regulatory elements | Instability of the Northeast Greenland Ice Stream over the last 45,000 years OPEN | | Nicolaj K. Larsen, Laura B. Levy, Anders E. Carlson, Christo Buizert, Jesper Olsen, Astrid Strunk, Anders A. Bjørk & Daniel S. Skov | | The outlet glaciers that comprise the Northeast Greenland Ice Stream (NEGIS) have experienced accelerated retreat in recent years, yet their longterm stability remains unclear. Here, via cosmogenic surface exposure and radiocarbon ages, the authors investigate the stability of the NEGIS for the past 45 kyr. | | 14 May 2018 | doi: 10.1038/s41467-018-04312-7 | | Cryospheric science Palaeoclimate | Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors OPEN | | Manuel Rodrigues , Lenha Mobuchon, Alexandre Houy, Alice Fiévet, Sophie Gardrat, Raymond L. Barnhill, Tatiana Popova, Vincent Servois, Aurore Rampanou, Aurore Mouton, Stéphane Dayot, Virginie Raynal, Michèle Galut, Marc Putterman, Sarah Tick, Nathalie Cassoux, Sergio Roman-Roman, François-Clément Bidard, Olivier Lantz, Pascale Mariani et al. | | Hypermutated tumors respond more favorably to checkpoint inhibitor-based immune therapy. Here, the authors describe a new hypermutated phenotype due to germline mutations and subsequent somatic loss of heterozygosity of MBD4, and a dramatic response to the PD-1 inhibitor pembrolizumab in a patient with a MBD4-inactivated hypermutated uveal melanoma. | | 14 May 2018 | doi: 10.1038/s41467-018-04322-5 | | Cancer genetics Eye cancer | Evolutionary instability of CUG-Leu in the genetic code of budding yeasts OPEN | | Tadeusz Krassowski, Aisling Y. Coughlan, Xing-Xing Shen, Xiaofan Zhou, Jacek Kominek, Dana A. Opulente, Robert Riley, Igor V. Grigoriev, Nikunj Maheshwari, Denis C. Shields, Cletus P. Kurtzman, Chris Todd Hittinger, Antonis Rokas & Kenneth H. Wolfe | | The genetic code for amino acids is nearly universal, and among eukaryotic nuclear genomes the only known reassignments are of codon CUG in yeasts. Here, the authors identify a third independent CUG transition in budding yeasts that is still ongoing with alternative tRNAs present in the genome. | | 14 May 2018 | doi: 10.1038/s41467-018-04374-7 | | Evolutionary biology Molecular evolution tRNAs | Top-down descending facilitation of spinal sensory excitatory transmission from the anterior cingulate cortex OPEN | | Tao Chen, Wataru Taniguchi, Qi-Yu Chen, Hidetoshi Tozaki-Saitoh, Qian Song, Ren-Hao Liu, Kohei Koga, Tsuyoshi Matsuda, Yae Kaito-Sugimura, Jian Wang, Zhi-Hua Li, Ya-Cheng Lu, Kazuhide Inoue, Makoto Tsuda, Yun-Qing Li, Terumasa Nakatsuka & Min Zhuo | | It is known that descending facilitation of spinal responses may contribute to chronic pain, however many studies have focussed on brainstem mechanisms. Here the authors show that stimulation of the anterior cingulate cortex increases excitatory transmission in the dorsal horn, and that this may be via a direct pathway independent of the brainstem. | | 14 May 2018 | doi: 10.1038/s41467-018-04309-2 | | Chronic pain Sensory processing | The rise of South–South trade and its effect on global CO2 emissions OPEN | | Jing Meng, Zhifu Mi, Dabo Guan, Jiashuo Li, Shu Tao, Yuan Li, Kuishuang Feng, Junfeng Liu, Zhu Liu, Xuejun Wang, Qiang Zhang & Steven J. Davis | | The rapid growth of South–South trade reflects a new phase of globalization. Here the authors show that some energy-intensive production activities, particularly raw materials and intermediate goods, and related CO2 emissions are relocating from China and India to other developing countries. | | 14 May 2018 | doi: 10.1038/s41467-018-04337-y | | Climate change Climate-change policy Developing world Environmental economics | Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases OPEN | | Adriana I. Iglesias , Aniket Mishra, Veronique Vitart, Yelena Bykhovskaya, René Höhn, Henriët Springelkamp, Gabriel Cuellar-Partida, Puya Gharahkhani, Jessica N. Cooke Bailey, Colin E. Willoughby, Xiaohui Li, Seyhan Yazar, Abhishek Nag, Anthony P. Khawaja, Ozren Polašek, David Siscovick, Paul Mitchell, Yih Chung Tham, Jonathan L. Haines, Lisa S. Kearns et al. | | Reduced central corneal thickness (CCT) is observed in common eye diseases as well as in rare Mendelian disorders. Here, in a cross-ancestry GWAS, the authors identify 19 novel genetic loci associated with CCT, a subset of which is involved in rare corneal or connective tissue disorders. | | 14 May 2018 | doi: 10.1038/s41467-018-03646-6 | | Genetics of the nervous system Genetics research Genome-wide association studies Hereditary eye disease | Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses OPEN | | Lars E. Clark, Selma Mahmutovic, Donald D. Raymond, Taleen Dilanyan, Takaaki Koma, John T. Manning, Sundaresh Shankar, Silvana C. Levis, Ana M. Briggiler, Delia A. Enria, Kai W. Wucherpfennig, Slobodan Paessler & Jonathan Abraham | | The five known New World hemorrhagic fever arenaviruses use the same entry receptor, but their viral glycoproteins are markedly different. Here, the authors isolate monoclonal antibodies from a Junin virus vaccinated person that cross-neutralize Machupo virus and identify a conserved epitope in the receptor-binding domain. | | 14 May 2018 | doi: 10.1038/s41467-018-04271-z | | Antibodies Arenaviruses Immunological memory Vaccines | Controlling evanescent waves using silicon photonic all-dielectric metamaterials for dense integration OPEN | | Saman Jahani, Sangsik Kim, Jonathan Atkinson, Justin C. Wirth, Farid Kalhor, Abdullah Al Noman, Ward D. Newman, Prashant Shekhar, Kyunghun Han, Vien Van, Raymond G. DeCorby, Lukas Chrostowski, Minghao Qi & Zubin Jacob | | Miniaturization of optical components could give way to dense photonic-integrated circuits. Here, the authors demonstrate the control of evanescent waves using all-dielectric metamaterials and show that they can reduce cross-talk and bending loss, which limit the integration density in photonic circuits. | | 14 May 2018 | doi: 10.1038/s41467-018-04276-8 | | Metamaterials Nanophotonics and plasmonics Sub-wavelength optics | Global genetic differentiation of complex traits shaped by natural selection in humans OPEN | | Jing Guo, Yang Wu, Zhihong Zhu, Zhili Zheng, Maciej Trzaskowski, Jian Zeng, Matthew R. Robinson, Peter M. Visscher & Jian Yang | | Human complex traits and disorders often show differentiation among populations. Here, the authors analyze SNPs associated with 10 complex traits using data of large sample size from African, East Asian and European populations, and find significant genetic differentiation among global populations shaped by natural selection. | | 14 May 2018 | doi: 10.1038/s41467-018-04191-y | | Evolutionary genetics Genetic association study | CO2-sensitive tRNA modification associated with human mitochondrial disease OPEN | | Huan Lin, Kenjyo Miyauchi, Tai Harada, Ryo Okita, Eri Takeshita, Hirofumi Komaki, Kaoru Fujioka, Hideki Yagasaki, Yu-ichi Goto, Kaori Yanaka, Shinichi Nakagawa, Yuriko Sakaguchi & Tsutomu Suzuki | | Transfer RNA modifications play critical roles in protein synthesis. Here the authors reveal the t6A37 tRNA modification is dynamically regulated by sensing intracellular CO2 concentration in mitochondria, implying metabolic regulation of protein synthesis. | | 14 May 2018 | doi: 10.1038/s41467-018-04250-4 | | RNA RNA modification | Parental haplotype-specific single-cell transcriptomics reveal incomplete epigenetic reprogramming in human female germ cells OPEN | | Ábel Vértesy, Wibowo Arindrarto, Matthias S. Roost, Björn Reinius, Vanessa Torrens-Juaneda, Monika Bialecka, Ioannis Moustakas, Yavuz Ariyurek, Ewart Kuijk, Hailiang Mei, Rickard Sandberg, Alexander van Oudenaarden & Susana M. Chuva de Sousa Lopes | | In mammalian female germ cells, parent-specific epigenetic marks are erased and the X chromosome reactivated before entry into meiosis. Here, by combining parental haplotype reconstruction with single-cell transcriptomics of human female embryonic germ cells, the authors demonstrate that epigenetic reprogramming occurs in a heterogeneous fashion and during a broad time window up to week 14. | | 14 May 2018 | doi: 10.1038/s41467-018-04215-7 | | Embryogenesis Imprinting Oogenesis | Cell of origin and mutation pattern define three clinically distinct classes of sebaceous carcinoma OPEN | | Jeffrey P. North, Justin Golovato, Charles J. Vaske, J. Zachary Sanborn, Andrew Nguyen, Wei Wu, Benjamin Goode, Meredith Stevers, Kevin McMullen, Bethany E. Perez White, Eric A. Collisson, Michele Bloomer, David A. Solomon, Stephen C. Benz & Raymond J. Cho | | Sebaceous carcinomas (SeC) are cutaneous malignancies that sometimes metastasize and cause death. Here the authors perform whole-exome sequencing on 32 SeC and report distinct mutational classes that may explain cancer ontogeny and clinical outcome. | | 14 May 2018 | doi: 10.1038/s41467-018-04008-y | | Cancer genomics Skin cancer | Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks OPEN | | Teppei Ebina, Yoshito Masamizu, Yasuhiro R. Tanaka, Akiya Watakabe, Reiko Hirakawa, Yuka Hirayama, Riichiro Hira, Shin-Ichiro Terada, Daisuke Koketsu, Kazuo Hikosaka, Hiroaki Mizukami, Atsushi Nambu, Erika Sasaki, Tetsuo Yamamori & Masanori Matsuzaki | | Marmosets are an important model organism in neuroscience but there has only been limited success in training them on behavioral tasks. Here the authors report their ability to train marmosets in various motor tasks and simultaneously image neural dynamics in motor cortex with 2-photon imaging. | | 14 May 2018 | doi: 10.1038/s41467-018-04286-6 | | Behavioural methods Ca2+ imaging Motor cortex | Cyclin K regulates prereplicative complex assembly to promote mammalian cell proliferation OPEN | | Tingjun Lei, Peixuan Zhang, Xudong Zhang, Xue Xiao, Jingli Zhang, Tong Qiu, Qian Dai, Yujun Zhang, Ling Min, Qian Li, Rutie Yin, Ping Ding, Ni Li, Yi Qu, Dezhi Mu, Jun Qin, Xiaofeng Zhu, Zhi-Xiong Xiao & Qintong Li | | Prereplicative complex (pre-RC) formation during G1 is fundamental for cell replication. Here the authors report a role for cyclin K in regulating pre-RC formation in mammalian cells by affecting cyclin E1 activity. | | 14 May 2018 | doi: 10.1038/s41467-018-04258-w | | Cancer Cell division DNA replication | Regulatory protein SrpA controls phage infection and core cellular processes in Pseudomonas aeruginosa OPEN | | Jiajia You, Li Sun, Xiaojing Yang, Xuewei Pan, Zhiwei Huang, Xixi Zhang, Mengxin Gong, Zheng Fan, Lingyan Li, Xiaoli Cui, Zhaoyuan Jing, Shouguang Jin, Zhiming Rao, Weihui Wu & Hongjiang Yang | | You et al. show that SrpA, a small protein widely conserved among bacteria, controls core cellular processes in response to phage infection and environmental signals in Pseudomonas aeruginosa, including cell motility, chemotaxis, biofilm formation, and virulence. | | 10 May 2018 | doi: 10.1038/s41467-018-04232-6 | | Bacterial evolution Bacterial genetics Phage biology | Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance OPEN | | Stephen J. Pettitt , Dragomir B. Krastev, Inger Brandsma, Amy Dréan, Feifei Song, Radoslav Aleksandrov, Maria I. Harrell, Malini Menon, Rachel Brough, James Campbell, Jessica Frankum, Michael Ranes, Helen N. Pemberton, Rumana Rafiq, Kerry Fenwick, Amanda Swain, Sebastian Guettler, Jung-Min Lee, Elizabeth M. Swisher, Stoyno Stoynov et al. | | The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, suggesting alternative resistance mechanisms. | | 10 May 2018 | doi: 10.1038/s41467-018-03917-2 | | Cancer genomics CRISPR-Cas9 genome editing DNA damage response | Chiral Landau levels in Weyl semimetal NbAs with multiple topological carriers OPEN | | Xiang Yuan , Zhongbo Yan, Chaoyu Song, Mengyao Zhang, Zhilin Li, Cheng Zhang, Yanwen Liu, Weiyi Wang, Minhao Zhao, Zehao Lin, Tian Xie, Jonathan Ludwig, Yuxuan Jiang, Xiaoxing Zhang, Cui Shang, Zefang Ye, Jiaxiang Wang, Feng Chen, Zhengcai Xia, Dmitry Smirnov et al. | | How the carriers behave in a Weyl semimetal if they occupy the lowest Landau level remains elusive. Here, the authors report evidences of electrons occupying zeroth chiral Landau levels with distinct linear dispersion behaviors for two inequivalent Weyl nodes in a Weyl semimetal NbAs. | | 10 May 2018 | doi: 10.1038/s41467-018-04080-4 | | Topological matter | TGF-β induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression OPEN | | Silvia Ottaviani, Justin Stebbing, Adam E. Frampton, Sladjana Zagorac, Jonathan Krell, Alexander de Giorgio, Sara M. Trabulo, Van T. M. Nguyen, Luca Magnani, Hugang Feng, Elisa Giovannetti, Niccola Funel, Thomas M. Gress, Long R. Jiao, Ylenia Lombardo, Nicholas R. Lemoine, Christopher Heeschen & Leandro Castellano | | In pancreatic ductal adenocarcinoma, TGF-β/Activin induce epithelial-to-mesenchymal transition (EMT) and stemness. Here, the authors show that TGF-β induces pro-tumourigenic miR-100 and miR-125b, but blocks anti-tumourigenic let-7a maturation via LIN28B, regulating pathways to promote stemness, EMT and tumourigenesis. | | 10 May 2018 | doi: 10.1038/s41467-018-03962-x | | Cancer stem cells Cell biology | The thioredoxin-1 system is essential for fueling DNA synthesis during T-cell metabolic reprogramming and proliferation OPEN | | Jonathan Muri, Sebastian Heer, Mai Matsushita, Lea Pohlmeier, Luigi Tortola, Tobias Fuhrer, Marcus Conrad, Nicola Zamboni, Jan Kisielow & Manfred Kopf | | Thioredoxin (Trx), Trx reductase, Txnip and NADPH together comprise the Trx system. Here the authors make a T cell-specific thioredoxin reductase-1 knockout mouse to show how this system reprograms cellular metabolism to enable T cell development, proliferation and responses. | | 10 May 2018 | doi: 10.1038/s41467-018-04274-w | | Cell death and immune response Lymphocyte activation | | |
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