Biological techniques

  • Article
    | Open Access

    Progressive familial intrahepatic cholestasis type 3 is a disease caused by mutations in the gene encoding the multidrug resistance protein 3, and has limited treatment options. Here they show that adeno-associated virus mediated gene therapy prevents disease progression in a mouse disease model.

    • Nicholas D. Weber
    • , Leticia Odriozola
    • , Javier Martínez-García
    • , Veronica Ferrer
    • , Anne Douar
    • , Bernard Bénichou
    • , Gloria González-Aseguinolaza
    •  & Cristian Smerdou
  • Article
    | Open Access

    The Lys48-linked polyubiquitin-mediated proteasomal degradation in yeast depends on Cdc48 and its cofactors Ufd1 and Npl4. Here, the authors present crystal structures of Npl4 bound to Lys48-linked diubiquitin and the Npl4-binding motif of Ufd1, providing insights into the reaction mechanism of the Cdc48- Ufd1/Npl4 complex.

    • Yusuke Sato
    • , Hikaru Tsuchiya
    • , Atsushi Yamagata
    • , Kei Okatsu
    • , Keiji Tanaka
    • , Yasushi Saeki
    •  & Shuya Fukai
  • Article
    | Open Access

    The design of protein assemblies is a major thrust for biomolecular engineering and nanobiotechnology. Here the authors demonstrate a general mechanism for designing allosteric macromolecular assemblies and showcase a proof of concept for engineered allosteric protein assembly.

    • Luis A. Campos
    • , Rajendra Sharma
    • , Sara Alvira
    • , Federico M. Ruiz
    • , Beatriz Ibarra-Molero
    • , Mourad Sadqi
    • , Carlos Alfonso
    • , Germán Rivas
    • , Jose M. Sanchez-Ruiz
    • , Antonio Romero Garrido
    • , José M. Valpuesta
    •  & Victor Muñoz
  • Article
    | Open Access

    Magnetic resonance imaging (MRI) is widely used to study the rat brain. Here, the authors provide standardized MRI brain templates and descriptive atlases for the rat, incorporating both structural and functional MRI data, along with associated resources.

    • D. A. Barrière
    • , R. Magalhães
    • , A. Novais
    • , P. Marques
    • , E. Selingue
    • , F. Geffroy
    • , F. Marques
    • , J. Cerqueira
    • , J. C. Sousa
    • , F. Boumezbeur
    • , M. Bottlaender
    • , T. M. Jay
    • , A. Cachia
    • , N. Sousa
    •  & S. Mériaux
  • Article
    | Open Access

    Graft versus host disease (GvHD) still hinders allogeneic hematopoietic stem cell transplantation. Here, the authors use metabolomics to analyze two cohorts of paired transplant recipients and donors, identifying significant differences in both host- and microbiota-derived metabolites.

    • David Michonneau
    • , Eleonora Latis
    • , Emmanuel Curis
    • , Laetitia Dubouchet
    • , Sivapriya Ramamoorthy
    • , Brian Ingram
    • , Régis Peffault de Latour
    • , Marie Robin
    • , Flore Sicre de Fontbrune
    • , Sylvie Chevret
    • , Lars Rogge
    •  & Gérard Socié
  • Article
    | Open Access

    Multiplexed detection of luciferase-based sensors in the same sample is challenging and limited by the substrates’ emission spectra. Here the authors establish a system based on three different luciferases and sequential detection to achieve measurements of up to six parameters within the same experiment.

    • Alejandro Sarrion-Perdigones
    • , Lyra Chang
    • , Yezabel Gonzalez
    • , Tatiana Gallego-Flores
    • , Damian W. Young
    •  & Koen J. T. Venken
  • Article
    | Open Access

    Particle manipulation is still challenging even with the many tools available, especially manipulating particles on a surface. Here, the authors report a technique for nanomanipulation of various objects on solid substrates by modulating particle-substrate interactions through laser-induced opto-thermal dynamics.

    • Jingang Li
    • , Yaoran Liu
    • , Linhan Lin
    • , Mingsong Wang
    • , Taizhi Jiang
    • , Jianhe Guo
    • , Hongru Ding
    • , Pavana Siddhartha Kollipara
    • , Yuji Inoue
    • , Donglei Fan
    • , Brian A. Korgel
    •  & Yuebing Zheng
  • Article
    | Open Access

    Here, the authors report parametric down-conversion of X-rays into long wavelength radiation in gallium arsenide and lithium niobate crystals, with efficiencies about 4 orders of magnitude stronger than the efficiencies measured in any material studied previously. They explore the lack of inversion symmetry as a possible physical mechanism.

    • S. Sofer
    • , O. Sefi
    • , E. Strizhevsky
    • , H. Aknin
    • , S. P. Collins
    • , G. Nisbet
    • , B. Detlefs
    • , Ch. J. Sahle
    •  & S. Shwartz
  • Article
    | Open Access

    Most cases of autosomal dominant polycystic kidney disease (ADPKD) are due to mutations in PKD1. Here, Tsukiyama et al. generate monkeys with mutations in PKD1 and show that animals recapitulate key pathological features of the human disease, suggesting these may provide insights into ADPKD pathogenesis and contribute to the development of future therapeutic strategies.

    • Tomoyuki Tsukiyama
    • , Kenichi Kobayashi
    • , Masataka Nakaya
    • , Chizuru Iwatani
    • , Yasunari Seita
    • , Hideaki Tsuchiya
    • , Jun Matsushita
    • , Kahoru Kitajima
    • , Ikuo Kawamoto
    • , Takahiro Nakagawa
    • , Koji Fukuda
    • , Teppei Iwakiri
    • , Hiroyuki Izumi
    • , Iori Itagaki
    • , Shinji Kume
    • , Hiroshi Maegawa
    • , Ryuichi Nishinakamura
    • , Saori Nishio
    • , Shinichiro Nakamura
    • , Akihiro Kawauchi
    •  & Masatsugu Ema
  • Article
    | Open Access

    Engineered biological nanopores enable observation of single molecule chemistry events; however a cylindrical pore geometry can have undesired effects. The authors report a conical biological pore which was embedded with tetrachloroaurate(III) to allow for discrimination between different biothiols.

    • Jiao Cao
    • , Wendong Jia
    • , Jinyue Zhang
    • , Xiumei Xu
    • , Shuanghong Yan
    • , Yuqin Wang
    • , Panke Zhang
    • , Hong-Yuan Chen
    •  & Shuo Huang
  • Article
    | Open Access

    Artificial nanopores can perform selective gating of molecules analogous to transmembrane proteins. Here, the authors design a DNA origami pore with a controllable lid for size-selective gating and translocation of macromolecules and evaluate its biosensing properties by single particle assay.

    • Rasmus P. Thomsen
    • , Mette Galsgaard Malle
    • , Anders Hauge Okholm
    • , Swati Krishnan
    • , Søren S.-R. Bohr
    • , Rasmus Schøler Sørensen
    • , Oliver Ries
    • , Stefan Vogel
    • , Friedrich C. Simmel
    • , Nikos S. Hatzakis
    •  & Jørgen Kjems
  • Article
    | Open Access

    Performing intravital imaging of the colon in mouse models is challenging due to the colon’s anatomic location and motility. Here, the authors develop a murine colonic window for intravital chronic imaging that maximises long-term animal survival and minimises motion artefacts.

    • Nikolai Rakhilin
    • , Aliesha Garrett
    • , Chi-Yong Eom
    • , Katherine Ramos Chavez
    • , David M. Small
    • , Andrea R. Daniel
    • , Melanie M. Kaelberer
    • , Menansili A. Mejooli
    • , Qiang Huang
    • , Shengli Ding
    • , David G. Kirsch
    • , Diego V. Bohórquez
    • , Nozomi Nishimura
    • , Bradley B. Barth
    •  & Xiling Shen
  • Article
    | Open Access

    Multiple sequence alignments of proteins carry information about evolution, the protein’s fitness landscape and its stability in the face of mutations. Here, the authors demonstrate the utility of latent space models learned using variational autoencoders to infer these properties from sequences.

    • Xinqiang Ding
    • , Zhengting Zou
    •  & Charles L. Brooks III
  • Article
    | Open Access

    Plasmodium growth is adapted to the reproductive cycle of mosquitoes, but underlying mechanisms are unclear. Here, Lampe et al. show that the blood-meal induced miR-276 balances the termination of the mosquito amino acid catabolism and egg development, providing nutrients for Plasmodium sporozoite development.

    • Lena Lampe
    • , Marius Jentzsch
    • , Sylwia Kierszniowska
    •  & Elena A. Levashina
  • Article
    | Open Access

    N6-methyladenosine (m6A) and N6,2′-O-dimethyladenosine (m6Am) are eukaryotic mRNA modifications. Here the authors develop m6A-Crosslinking-Exonuclease-sequencing to map quantitative methylome changes at single-base-resolution after individually knocking out each known methyltransferase or demethylase.

    • Casslynn W. Q. Koh
    • , Yeek Teck Goh
    •  & W. S. Sho Goh
  • Article
    | Open Access

    Semiconductor quantum dots are controlled by external fields that are tuned in order to optimise for information storage or inter-qubit interaction. Here the authors identify a working point for long-range interactions that can be reached with continuous protection from environmental noise.

    • J. C. Abadillo-Uriel
    • , M. A. Eriksson
    • , S. N. Coppersmith
    •  & Mark Friesen
  • Article
    | Open Access

    Although most are silenced, certain transposable elements (TEs) have been co-opted by the host. Here, the authors quantify the epigenomic status of TEs using data from the Roadmap Epigenomics Project, provide a systematic profile of TE activity across normal human tissues and development, finding that TEs encompass a quarter of the human regulatory epigenome, with 47% of TEs in regulatory states.

    • Erica C. Pehrsson
    • , Mayank N. K. Choudhary
    • , Vasavi Sundaram
    •  & Ting Wang
  • Article
    | Open Access

    Myeloid-derived growth factor (MYDGF) is an endoplasmic reticulum protein of therapeutic interest because it promotes tissue repair in a murine model of myocardial infarction. Here the authors present the NMR structure of human MYDGF and attribute function to a set of residues conserved in MYDGFs but not the vanin base domain, which has a similar fold.

    • Valeriu Bortnov
    • , Marco Tonelli
    • , Woonghee Lee
    • , Ziqing Lin
    • , Douglas S. Annis
    • , Omar N. Demerdash
    • , Alex Bateman
    • , Julie C. Mitchell
    • , Ying Ge
    • , John L. Markley
    •  & Deane F. Mosher
  • Article
    | Open Access

    Here, Bhattacharya et al. chemically mutagenize Leishmania and identify genes associated with resistance to miltefosine and paromomycin by next generation sequencing. The study shows that a protein kinase (CDPK1) can mediate resistance to paromomycin by affecting translation.

    • Arijit Bhattacharya
    • , Philippe Leprohon
    • , Sophia Bigot
    • , Prasad Kottayil Padmanabhan
    • , Angana Mukherjee
    • , Gaétan Roy
    • , Hélène Gingras
    • , Anais Mestdagh
    • , Barbara Papadopoulou
    •  & Marc Ouellette
  • Article
    | Open Access

    Glycolysis is elevated in many cancers. In this study, the authors show that lactoylglutathione, a by-product of methylglyoxal produced from increased glycolysis, is elevated in lung cancer in mouse models and humans, arguing reactive metabolite production can be a liability for cancers.

    • Alba Luengo
    • , Keene L. Abbott
    • , Shawn M. Davidson
    • , Aaron M. Hosios
    • , Brandon Faubert
    • , Sze Ham Chan
    • , Elizaveta Freinkman
    • , Lauren G. Zacharias
    • , Thomas P. Mathews
    • , Clary B. Clish
    • , Ralph J. DeBerardinis
    • , Caroline A. Lewis
    •  & Matthew G. Vander Heiden
  • Article
    | Open Access

    Relapse, reinfection and recrudescence can all cause recurrent infection after treatment of Plasmodium vivax malaria in endemic areas, but are difficult to distinguish. Here the authors show that they can be differentiated probabilistically and thereby demonstrate the high efficacy of primaquine treatment in preventing relapse.

    • Aimee R. Taylor
    • , James A. Watson
    • , Cindy S. Chu
    • , Kanokpich Puaprasert
    • , Jureeporn Duanguppama
    • , Nicholas P. J. Day
    • , Francois Nosten
    • , Daniel E. Neafsey
    • , Caroline O. Buckee
    • , Mallika Imwong
    •  & Nicholas J. White
  • Article
    | Open Access

    Ni–Fe based compound are known as active electrocatalysts for oxygen evolution reaction, but not a good choice for the other half-reaction of water-splitting. Here the authors report a unique interface between Ni and γ-Fe2O3 that efficiently catalyzes the cathodic hydrogen evolution reaction.

    • Bryan H. R. Suryanto
    • , Yun Wang
    • , Rosalie K. Hocking
    • , William Adamson
    •  & Chuan Zhao
  • Article
    | Open Access

    Compared to single nucleotide variants and short indels, structural variants (SVs) are often more challenging to detect using high-throughput sequencing based methods. Here, the authors develop LinkedSV, a computational tool for SV detection using linked-read exome and genome sequencing data.

    • Li Fang
    • , Charlly Kao
    • , Michael V. Gonzalez
    • , Fernanda A. Mafra
    • , Renata Pellegrino da Silva
    • , Mingyao Li
    • , Sören-Sebastian Wenzel
    • , Katharina Wimmer
    • , Hakon Hakonarson
    •  & Kai Wang
  • Article
    | Open Access

    Cysteinyl leukotriene G protein-coupled receptors CysLT1 and CysLT2 regulate pro-inflammatory responses associated with allergic disorders. Here, authors describe four crystal structures of CysLT2R in complex with three dual CysLT1R/CysLT2R antagonists, which shed light on CysLTR ligand selectivity.

    • Anastasiia Gusach
    • , Aleksandra Luginina
    • , Egor Marin
    • , Rebecca L. Brouillette
    • , Élie Besserer-Offroy
    • , Jean-Michel Longpré
    • , Andrii Ishchenko
    • , Petr Popov
    • , Nilkanth Patel
    • , Taku Fujimoto
    • , Toru Maruyama
    • , Benjamin Stauch
    • , Margarita Ergasheva
    • , Daria Romanovskaia
    • , Anastasiia Stepko
    • , Kirill Kovalev
    • , Mikhail Shevtsov
    • , Valentin Gordeliy
    • , Gye Won Han
    • , Vsevolod Katritch
    • , Valentin Borshchevskiy
    • , Philippe Sarret
    • , Alexey Mishin
    •  & Vadim Cherezov
  • Article
    | Open Access

    Although polarized Raman microscopy is sensitive to orientation changes, quantitative information has been missing. Here, the authors use simultaneous registration of multiple Raman scattering spectra obtained at different polarizations and show quantitative orientation mapping

    • Oleksii Ilchenko
    • , Yuriy Pilgun
    • , Andrii Kutsyk
    • , Florian Bachmann
    • , Roman Slipets
    • , Matteo Todeschini
    • , Peter Ouma Okeyo
    • , Henning Friis Poulsen
    •  & Anja Boisen
  • Article
    | Open Access

    How a precancerous form (dysplasia) becomes gastric cancer is unclear. Here, the authors assess the role of Kras activation in heterogenous dysplastic cells in murine stomach corpus organoids, identifying two dysplastic stem cell populations and show that MEK inhibition causes alterations in cell behavior.

    • Jimin Min
    • , Paige N. Vega
    • , Amy C. Engevik
    • , Janice A. Williams
    • , Qing Yang
    • , Loraine M. Patterson
    • , Alan J. Simmons
    • , R. Jarrett Bliton
    • , Joshua W. Betts
    • , Ken S. Lau
    • , Scott T. Magness
    • , James R. Goldenring
    •  & Eunyoung Choi
  • Article
    | Open Access

    Addition of small nanoparticles into polymer melt can lead to decrease in viscosity but the underlying mechanism for such viscosity reduction remains unclear. Here, the authors investigate the reduction in viscosity by large-scale molecular dynamics simulation and experimental rheology measurements for an all-polymer nanocomposite formed by linear polystyrene chains and PS single-chain nanoparticle.

    • Tao Chen
    • , Huan-Yu Zhao
    • , Rui Shi
    • , Wen-Feng Lin
    • , Xiang-Meng Jia
    • , Hu-Jun Qian
    • , Zhong-Yuan Lu
    • , Xing-Xing Zhang
    • , Yan-Kai Li
    •  & Zhao-Yan Sun
  • Article
    | Open Access

    SPOR domains are present in bacterial proteins that recognize cell-wall peptidoglycan strands stripped of the peptide stems. Here, Alcorlo et al. show that, indeed, the presence of peptide stems abrogates binding to a SPOR domain, and provide insights into the molecular basis for recognition.

    • Martín Alcorlo
    • , David A. Dik
    • , Stefania De Benedetti
    • , Kiran V. Mahasenan
    • , Mijoon Lee
    • , Teresa Domínguez-Gil
    • , Dusan Hesek
    • , Elena Lastochkin
    • , Daniel López
    • , Bill Boggess
    • , Shahriar Mobashery
    •  & Juan A. Hermoso
  • Article
    | Open Access

    Probing inevitable defects in two- dimensional materials is challenging. Here, the authors tackle this issue by using tip-enhanced Raman spectroscopy (TERS) to obtain distinctly different Raman features of edge defects in atomically thin MoS2, and further probe their unique electronic properties as well as identify the armchair and zigzag edges.

    • Teng-Xiang Huang
    • , Xin Cong
    • , Si-Si Wu
    • , Kai-Qiang Lin
    • , Xu Yao
    • , Yu-Han He
    • , Jiang-Bin Wu
    • , Yi-Fan Bao
    • , Sheng-Chao Huang
    • , Xiang Wang
    • , Ping-Heng Tan
    •  & Bin Ren
  • Article
    | Open Access

    Siblings of those with autism spectrum disorder (ASD) have increased likelihood of ASD or related subclinical traits. Here, studying 253 ASD families, D’Abate et al. test the predictive value of genomic copy number variation involving ASD-associated loci, with confirmation in a second cohort.

    • L. D’Abate
    • , S. Walker
    • , R. K. C. Yuen
    • , K. Tammimies
    • , J. A. Buchanan
    • , R. W. Davies
    • , B. Thiruvahindrapuram
    • , J. Wei
    • , J. Brian
    • , S. E. Bryson
    • , K. Dobkins
    • , J. Howe
    • , R. Landa
    • , J. Leef
    • , D. Messinger
    • , S. Ozonoff
    • , I. M. Smith
    • , W. L. Stone
    • , Z. E. Warren
    • , G. Young
    • , L. Zwaigenbaum
    •  & S. W. Scherer
  • Article
    | Open Access

    MLL family histone methyltransferases deposit histone H3 Lys4 mono-/di-/tri-methylation and regulate gene expression in mammals. Here the authors report the single-particle cryo-EM structure of the NCP-bound human MLL1 core complex, shedding light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.

    • Sang Ho Park
    • , Alex Ayoub
    • , Young-Tae Lee
    • , Jing Xu
    • , Hanseong Kim
    • , Wei Zheng
    • , Biao Zhang
    • , Liang Sha
    • , Sojin An
    • , Yang Zhang
    • , Michael A. Cianfrocco
    • , Min Su
    • , Yali Dou
    •  & Uhn-Soo Cho
  • Article
    | Open Access

    RNA polymerase I (Pol I) catalyses the transcription of pre-ribosomal RNA and for transcription initiation Pol I assembles with core factor and Rrn3 on the rDNA core promoter. Here the authors provide insights into the molecular mechanism of promoter opening by Pol I by determining the cryo-EM structures of two closed, two intermediate and two open Pol I pre-initiation complexes.

    • Yashar Sadian
    • , Florence Baudin
    • , Lucas Tafur
    • , Brice Murciano
    • , Rene Wetzel
    • , Felix Weis
    •  & Christoph W. Müller
  • Article
    | Open Access

    Tightly controlling cell output is challenging, which has limited development and applications of bacterial sensors. Here the authors develop tunable, fast-responding sensors to control production of metabolic pigments and use them to assess zinc deficiency in a low-cost, minimal equipment fashion.

    • Monica P. McNerney
    • , Cirstyn L. Michel
    • , Krishi Kishore
    • , Janet Standeven
    •  & Mark P. Styczynski
  • Article
    | Open Access

    Vertically stacked twisted layers of two-dimensional materials can trigger exciting fundamental physics. Here, authors report controlled growth of 30° twisted few-layer SnS2 over SnS2 via van der Waals epitaxy of an SnS intermediate and its transformation in the presence of excess sulfur.

    • Peter Sutter
    • , Rina Ibragimova
    • , Hannu-Pekka Komsa
    • , Bruce A. Parkinson
    •  & Eli Sutter
  • Article
    | Open Access

    The off-target effects and on-target mutations of CRISPR editing in higher non-human primates are complex. Here the authors perform whole genome trio sequencing of rhesus monkeys and see no unexpected mutations.

    • Xin Luo
    • , Yaoxi He
    • , Chao Zhang
    • , Xiechao He
    • , Lanzhen Yan
    • , Min Li
    • , Ting Hu
    • , Yan Hu
    • , Jin Jiang
    • , Xiaoyu Meng
    • , Weizhi Ji
    • , Xudong Zhao
    • , Ping Zheng
    • , Shuhua Xu
    •  & Bing Su
  • Article
    | Open Access

    Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are characterized by the pathological accumulation of α-synuclein. Here the authors employ fluorescent probes, electron microscopy and NMR spectroscopy to study the properties of α-synuclein aggregates that were amplified from patient brain extracts and observe a greater structural diversity among PD patients compared to MSA patients.

    • Timo Strohäker
    • , Byung Chul Jung
    • , Shu-Hao Liou
    • , Claudio O. Fernandez
    • , Dietmar Riedel
    • , Stefan Becker
    • , Glenda M. Halliday
    • , Marina Bennati
    • , Woojin S. Kim
    • , Seung-Jae Lee
    •  & Markus Zweckstetter
  • Article
    | Open Access

    CRISPR-Cas systems have well characterized, modular structures. Here the authors use that architecture to design a Cas12a library of 560 synthetic chimeras, with altered PAM preferences and specificities.

    • R. M. Liu
    • , L. L. Liang
    • , E. Freed
    • , H. Chang
    • , E. Oh
    • , Z. Y. Liu
    • , A. Garst
    • , C. A. Eckert
    •  & R. T. Gill
  • Article
    | Open Access

    Thermal characterization of biological tissues can traditionally provide either large fields of view or high resolution. By the development of super-resolution infrared photo-thermal imaging, the authors reconstruct temperature-based maps of absorptive centers in millimeter-sized biological samples.

    • M. Bouzin
    • , M. Marini
    • , A. Zeynali
    • , M. Borzenkov
    • , L. Sironi
    • , L. D’Alfonso
    • , F. Mingozzi
    • , F. Granucci
    • , P. Pallavicini
    • , G. Chirico
    •  & M. Collini
  • Article
    | Open Access

    Many approaches exist to process data from individual imaging modalities, but integrating them is challenging. The authors develop an automated resource that enables co-registered network- and tract-level analysis of macroscopic in-vivo imaging and microscopic imaging of cleared tissue.

    • Maged Goubran
    • , Christoph Leuze
    • , Brian Hsueh
    • , Markus Aswendt
    • , Li Ye
    • , Qiyuan Tian
    • , Michelle Y. Cheng
    • , Ailey Crow
    • , Gary K. Steinberg
    • , Jennifer A. McNab
    • , Karl Deisseroth
    •  & Michael Zeineh
  • Article
    | Open Access

    The conformational heterogeneity of RNA molecules makes their structure determination by X-ray crystallography and NMR challenging. Here the authors show that RNA structures can be solved by cryo-EM and present the structures of a 40 kDa SAM-IV riboswitch in the apo form and bound to its ligand S-adenosylmethionine.

    • Kaiming Zhang
    • , Shanshan Li
    • , Kalli Kappel
    • , Grigore Pintilie
    • , Zhaoming Su
    • , Tung-Chung Mou
    • , Michael F. Schmid
    • , Rhiju Das
    •  & Wah Chiu
  • Article
    | Open Access

    The activation mechanism of integrin αVβ8 differs from other integrins. Combining X-ray crystallography, hydrogen deuterium exchange mass spectrometry and mutation, the authors reveal structural features responsible for these differences and provide insights into how typical integrins are regulated.

    • Jianchuan Wang
    • , Yang Su
    • , Roxana E. Iacob
    • , John R. Engen
    •  & Timothy A. Springer
  • Article
    | Open Access

    Many cancer cells have increased glucose consumption compared to normal cells, a feature that can be exploited therapeutically. Here, the authors carry out a chemical screen and identify compounds that selectively blocks glucose metabolism in non-small-cell lung cancer cell lines.

    • Chiara Ghezzi
    • , Alicia Wong
    • , Bao Ying Chen
    • , Bernard Ribalet
    • , Robert Damoiseaux
    •  & Peter M. Clark
  • Article
    | Open Access

    Inducible genome editing systems often suffer from leakiness or reduced activity. Here the authors develop CRISPR-Switch, a Cre recombinase ON/OFF-controlled sgRNA cassette that allows consecutive editing of two loci.

    • Krzysztof Chylinski
    • , Maria Hubmann
    • , Ruth E. Hanna
    • , Connor Yanchus
    • , Georg Michlits
    • , Esther C. H. Uijttewaal
    • , John Doench
    • , Daniel Schramek
    •  & Ulrich Elling
  • Article
    | Open Access

    Anaplastic lymphoma kinase (ALK) inhibitors are currently being considered in neuroblastoma (NB), but its acquired resistance is reported in non-small cell lung cancers. Here, the authors have found PIM1 overexpression decreases sensitivity to ALK inhibitors in NB and combined ALK and PIM1 inhibition enhances anti-tumour efficacy in vitro and in PDX models.

    • Ricky M. Trigg
    • , Liam C. Lee
    • , Nina Prokoph
    • , Leila Jahangiri
    • , C. Patrick Reynolds
    • , G. A. Amos Burke
    • , Nicola A. Probst
    • , Miaojun Han
    • , Jamie D. Matthews
    • , Hong Kai Lim
    • , Eleanor Manners
    • , Sonia Martinez
    • , Joaquin Pastor
    • , Carmen Blanco-Aparicio
    • , Olaf Merkel
    • , Ines Garces de los Fayos Alonso
    • , Petra Kodajova
    • , Simone Tangermann
    • , Sandra Högler
    • , Ji Luo
    • , Lukas Kenner
    •  & Suzanne D. Turner
  • Article
    | Open Access

    t-SNE is widely used for dimensionality reduction and visualization of high-dimensional single-cell data. Here, the authors introduce a protocol to help avoid common shortcomings of t-SNE, for example, enabling preservation of the global structure of the data.

    • Dmitry Kobak
    •  & Philipp Berens
  • Article
    | Open Access

    DNA ligases catalyze the joining of DNA strands to complete DNA replication, recombination and repair transactions. Here the authors present X-ray structures and kinetic analyses of LIG1 complexes with undamaged and oxidatively damaged DNA that unveil determinants of LIG1 substrate recognition and enzymatic fidelity.

    • Percy P. Tumbale
    • , Thomas J. Jurkiw
    • , Matthew J. Schellenberg
    • , Amanda A. Riccio
    • , Patrick J O’Brien
    •  & R. Scott Williams