Diseases

  • 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

    Rap1 is a telomeric protein that is highly expressed in cancers. Here, the authors show that Rap1 interacts with several DNA repair proteins independent of its telomere function to enhance DNA repair and that its deficiency leads to accelerated tumorigenesis, but enhanced sensitivity to genotoxic stress.

    • Ekta Khattar
    • , Kyaw Ze Ya Maung
    • , Chen Li Chew
    • , Arkasubhra Ghosh
    • , Michelle Meng Huang Mok
    • , Pei Lee
    • , Jun Zhang
    • , Wei Hong Jeff Chor
    • , Gökhan Cildir
    • , Chelsia Qiuxia Wang
    • , Nur Khairiah Mohd-Ismail
    • , Desmond Wai Loon Chin
    • , Soo Chin Lee
    • , Henry Yang
    • , Yong-Jae Shin
    • , Do-Hyun Nam
    • , Liming Chen
    • , Alan Prem Kumar
    • , Lih Wen Deng
    • , Masahito Ikawa
    • , Jayantha Gunaratne
    • , Motomi Osato
    •  & Vinay Tergaonkar
  • Article
    | Open Access

    miRNA142-3p and Tet2 are separately known to regulate Treg. Here the authors show that miRNA142-3p targets Tet2 and by this opposes Treg differentiation in autoimmune diabetes.

    • Martin G. Scherm
    • , Isabelle Serr
    • , Adam M. Zahm
    • , Jonathan Schug
    • , Saverio Bellusci
    • , Rossella Manfredini
    • , Victoria K. Salb
    • , Katharina Gerlach
    • , Benno Weigmann
    • , Anette-Gabriele Ziegler
    • , Klaus H. Kaestner
    •  & Carolin Daniel
  • Article
    | Open Access

    Glioblastoma cells are known to be able to adapt easily to different environments. The authors study the dynamic adaptation of glioblastoma cells to the heterogenous brain tumor microenvironment, showing that tumor cells demonstrate varying plasticity of their transcriptomic profiles and an ability to survive new stimuli, in part, by propagating stochastic perturbations over their gene-regulatory network.

    • Orieta Celiku
    • , Mark R. Gilbert
    •  & Orit Lavi
  • Article
    | Open Access

    The authors report a co-occurrence of the U2AF1 S34F splicing factor mutation and ROS1 translocations in lung adenocarcinomas and profile effects of S34F on transcriptome-wide RNA binding. They further show that U2AF1 S34F enhances invasive potential and alters splicing of ROS1 fusion transcripts

    • Mohammad S. Esfahani
    • , Luke J. Lee
    • , Young-Jun Jeon
    • , Ryan A. Flynn
    • , Henning Stehr
    • , Angela B. Hui
    • , Noriko Ishisoko
    • , Eric Kildebeck
    • , Aaron M. Newman
    • , Scott V. Bratman
    • , Matthew H. Porteus
    • , Howard Y. Chang
    • , Ash A. Alizadeh
    •  & Maximilian Diehn
  • Article
    | Open Access

    The eye shows protective responses to noxious stimuli including cold. Here, the authors show that TRPV1, found co-expressed on TRPM8 + fibres in the cornea, is necessary for cold nociception in the eye.

    • Fengxian Li
    • , Weishan Yang
    • , Haowu Jiang
    • , Changxiong Guo
    • , Andrew J. W. Huang
    • , Hongzhen Hu
    •  & Qin Liu
  • Article
    | Open Access

    Primary cilia have been proposed to regulate glucose metabolism and insulin secretion in beta cells, but it is not known how. Here the authors show that primary cilia play a role in adult β-cell function via a mechanism involving endosomal EphA-processing.

    • Francesco Volta
    • , M. Julia Scerbo
    • , Anett Seelig
    • , Robert Wagner
    • , Nils O’Brien
    • , Felicia Gerst
    • , Andreas Fritsche
    • , Hans-Ulrich Häring
    • , Anja Zeigerer
    • , Susanne Ullrich
    •  & Jantje M. Gerdes
  • Article
    | Open Access

    Understanding the genomic features of dedifferentiated liposarcoma (DDLPS) is likely to uncover new options for management. Here, the authors reveal three prognostic groups, and highlight molecular markers associated with malignant transformation.

    • Makoto Hirata
    • , Naofumi Asano
    • , Kotoe Katayama
    • , Akihiko Yoshida
    • , Yusuke Tsuda
    • , Masaya Sekimizu
    • , Sachiyo Mitani
    • , Eisuke Kobayashi
    • , Motokiyo Komiyama
    • , Hiroyuki Fujimoto
    • , Takahiro Goto
    • , Yukihide Iwamoto
    • , Norifumi Naka
    • , Shintaro Iwata
    • , Yoshihiro Nishida
    • , Toru Hiruma
    • , Hiroaki Hiraga
    • , Hirotaka Kawano
    • , Toru Motoi
    • , Yoshinao Oda
    • , Daisuke Matsubara
    • , Masashi Fujita
    • , Tatsuhiro Shibata
    • , Hidewaki Nakagawa
    • , Robert Nakayama
    • , Tadashi Kondo
    • , Seiya Imoto
    • , Satoru Miyano
    • , Akira Kawai
    • , Rui Yamaguchi
    • , Hitoshi Ichikawa
    •  & Koichi Matsuda
  • Article
    | Open Access

    Lactobacillus associates with vaginal protection from HIV-1 infection. Here, the authors show that lactobacilli extracellular vesicles contain bacterial proteins and metabolites that inhibit HIV-1 infection in T cells and in human cervico-vaginal and tonsillar tissues ex vivo via altering viral Env proteins.

    • Rogers A. Ñahui Palomino
    • , Christophe Vanpouille
    • , Luca Laghi
    • , Carola Parolin
    • , Kamran Melikov
    • , Peter Backlund
    • , Beatrice Vitali
    •  & Leonid Margolis
  • Article
    | Open Access

    BRCA1 mutations located within the BRCT domain result in proteasomal degradation and sensitivity to PARP inhibitors (PARPi). Here, the authors report genetic rearrangements in the BRCA1 gene that generate a BRCT-less BRCA1 protein isoform, which avoids degradation and leads to PARPi resistance.

    • Yifan Wang
    • , Andrea J. Bernhardy
    • , Joseph Nacson
    • , John J. Krais
    • , Yin-Fei Tan
    • , Emmanuelle Nicolas
    • , Marc R. Radke
    • , Elizabeth Handorf
    • , Alba Llop-Guevara
    • , Judith Balmaña
    • , Elizabeth M. Swisher
    • , Violeta Serra
    • , Suraj Peri
    •  & Neil Johnson
  • Article
    | Open Access

    Gut microbiota alterations, including enrichment of flagellated bacteria, are associated with metabolic syndrome and chronic inflammatory diseases. Here, Tran et al. show, in mice, that elicitation of mucosal anti-flagellin antibodies protects against experimental colitis and ameliorates diet-induced obesity.

    • Hao Q. Tran
    • , Ruth E. Ley
    • , Andrew T. Gewirtz
    •  & Benoit Chassaing
  • Article
    | Open Access

    Effective precision medicine strategies rely on the ability to predict tumour behaviour based on molecular characteristics. Here, the authors build models to predict multiple distinct gene expression patterns using DNA copy number alterations

    • Youli Xia
    • , Cheng Fan
    • , Katherine A. Hoadley
    • , Joel S. Parker
    •  & Charles M. Perou
  • Article
    | Open Access

    PARG catalyzes the removal of poly(ADP-ribose) (PAR) from target proteins and executes critical functions in the DNA damage response. Here the authors provide structural and biological insight with small molecule PARG inhibitors and show that PARG inhibition sensitizes cells to ionizing radiation and kills cancer cells through replication fork defects.

    • Jerry H. Houl
    • , Zu Ye
    • , Chris A. Brosey
    • , Lakshitha P. F. Balapiti-Modarage
    • , Sarita Namjoshi
    • , Albino Bacolla
    • , Daniel Laverty
    • , Brian L. Walker
    • , Yasin Pourfarjam
    • , Leslie S. Warden
    • , Naga Babu Chinnam
    • , Davide Moiani
    • , Roderick A. Stegeman
    • , Mei-Kuang Chen
    • , Mien-Chie Hung
    • , Zachary D. Nagel
    • , Tom Ellenberger
    • , In-Kwon Kim
    • , Darin E. Jones
    • , Zamal Ahmed
    •  & John A. Tainer
  • 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

    The adipokine leptin modulates intestinal inflammation in mice. Here the authors describe a patient with inflammatory bowel disease and lipodystrophy, providing evidence that leptin aggravates intestinal inflammation with proinflammatory effects on leukocytes that are reversible by TNFα blockade.

    • Jörn F. Ziegler
    • , Chotima Böttcher
    • , Marilena Letizia
    • , Cansu Yerinde
    • , Hao Wu
    • , Inka Freise
    • , Yasmina Rodriguez-Sillke
    • , Ani K. Stoyanova
    • , Martin E. Kreis
    • , Patrick Asbach
    • , Desiree Kunkel
    • , Josef Priller
    • , Ioannis Anagnostopoulos
    • , Anja A. Kühl
    • , Konstanze Miehle
    • , Michael Stumvoll
    • , Florian Tran
    • , Broder Fredrich
    • , Michael Forster
    • , Andre Franke
    • , Christian Bojarski
    • , Rainer Glauben
    • , Britt-Sabina Löscher
    • , Britta Siegmund
    •  & Carl Weidinger
  • Article
    | Open Access

    Polymorphisms in LMO1 are associated with increased susceptibility to develop neuroblastoma. Here, the authors show that LMO1 directly induces the transcription factor ASCL1, which regulates the differentiation of neurons, demonstrating that ASCL1 is part of the adrenergic neuroblastoma core regulatory circuit.

    • Lu Wang
    • , Tze King Tan
    • , Adam D. Durbin
    • , Mark W. Zimmerman
    • , Brian J. Abraham
    • , Shi Hao Tan
    • , Phuong Cao Thi Ngoc
    • , Nina Weichert-Leahey
    • , Koshi Akahane
    • , Lee N. Lawton
    • , Jo Lynne Rokita
    • , John M. Maris
    • , Richard A. Young
    • , A. Thomas Look
    •  & Takaomi Sanda
  • 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

    The exact molecular mechanisms driving FUS-mediated toxicity remain unclear. Here, the authors demonstrate that muscleblind (Mbl) is a novel modifier of FUS-associated ALS, with knockdown of endogenous Mbl suppressing neuromuscular junction defects and motor dysfunctions associated with FUS expression in Drosophila, as well as restoring reduced SMN protein levels in mammalian neuronal and human iPSC-derived motor neurons.

    • Ian Casci
    • , Karthik Krishnamurthy
    • , Sukhleen Kour
    • , Vadreenath Tripathy
    • , Nandini Ramesh
    • , Eric N. Anderson
    • , Lara Marrone
    • , Rogan A. Grant
    • , Stacie Oliver
    • , Lauren Gochenaur
    • , Krishani Patel
    • , Jared Sterneckert
    • , Amanda M. Gleixner
    • , Christopher J. Donnelly
    • , Marc-David Ruepp
    • , Antonella M. Sini
    • , Emanuela Zuccaro
    • , Maria Pennuto
    • , Piera Pasinelli
    •  & Udai Bhan Pandey
  • 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

    The HLA-A*68:01 allele has been associated with severe influenza disease during the 2009 influenza pandemic. Here, the authors analyze influenza nucleoprotein specific HLA-A*68:01-restricted CD8+ T cells from human donors and show immunodominance of these cells in approximately 35% of HLA-A*68:01-expressing donors.

    • C. E. van de Sandt
    • , E. B. Clemens
    • , E. J. Grant
    • , L. C. Rowntree
    • , S. Sant
    • , H. Halim
    • , J. Crowe
    • , A. C. Cheng
    • , T. C. Kotsimbos
    • , M. Richards
    • , A. Miller
    • , S. Y. C. Tong
    • , J. Rossjohn
    • , T. H. O. Nguyen
    • , S. Gras
    • , W. Chen
    •  & K. Kedzierska
  • 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

    Intermediate transitions between epithelial and mesenchymal states are associated with tumor progression. Here using mass cytometry, Plevritis and colleagues develop a computational framework to resolve and map these trajectories in lung cancer cells and clinical specimens.

    • Loukia G. Karacosta
    • , Benedict Anchang
    • , Nikolaos Ignatiadis
    • , Samuel C. Kimmey
    • , Jalen A. Benson
    • , Joseph B. Shrager
    • , Robert Tibshirani
    • , Sean C. Bendall
    •  & Sylvia K. Plevritis
  • Article
    | Open Access

    Yamanaka factors can reprogram somatic and cancer cells into induced pluripotent stem cells. Here, the authors show that the induction of these factors in acute myeloid leukemia leads to apoptosis of leukemia cells in vivo, and this is through modulation of chromatin accessibility to apoptotic genes and accompanied by H3K9me3 dysregulation.

    • Yajie Wang
    • , Ting Lu
    • , Guohuan Sun
    • , Yawei Zheng
    • , Shangda Yang
    • , Hongyan Zhang
    • , Sha Hao
    • , Yanfeng Liu
    • , Shihui Ma
    • , Houyu Zhang
    • , Yongxin Ru
    • , Shaorong Gao
    • , Kuangyu Yen
    • , Hui Cheng
    •  & Tao Cheng
  • Article
    | Open Access

    Tobacco use is one of the major risk factors for Head and neck squamous cell carcinoma (HNSCC). Here, the authors report an immune-competent syngeneic mouse model that mimics human tobacco-related HNSCC, and develops tumors in the tongue, and report a high response rate to anti-CTLA-4 therapy.

    • Zhiyong Wang
    • , Victoria H. Wu
    • , Michael M. Allevato
    • , Mara Gilardi
    • , Yudou He
    • , Juan Luis Callejas-Valera
    • , Lynn Vitale-Cross
    • , Daniel Martin
    • , Panomwat Amornphimoltham
    • , James Mcdermott
    • , Bryan S. Yung
    • , Yusuke Goto
    • , Alfredo A. Molinolo
    • , Andrew B. Sharabi
    • , Ezra E. W. Cohen
    • , Qianming Chen
    • , J. Guy Lyons
    • , Ludmil B. Alexandrov
    •  & J. Silvio Gutkind
  • Article
    | Open Access

    Aurora-A kinase is frequently over-expressed in tumours. Here, the authors show that it modulates the activity of lactate dehydrogenase B, resulting in enhanced glycolysis, bio-synthesis and tumour growth.

    • Aoxing Cheng
    • , Peng Zhang
    • , Bo Wang
    • , Dongdong Yang
    • , Xiaotao Duan
    • , Yongliang Jiang
    • , Tian Xu
    • , Ya Jiang
    • , Jiahui Shi
    • , Chengtao Ding
    • , Gao Wu
    • , Zhihong Sang
    • , Qiang Wu
    • , Hua Wang
    • , Mian Wu
    • , Zhiyong Zhang
    • , Xin Pan
    • , Yue-yin Pan
    • , Ping Gao
    • , Huafeng Zhang
    • , Cong-zhao Zhou
    • , Jing Guo
    •  & Zhenye Yang
  • Article
    | Open Access

    Infection or chronic inflammation is a risk factor for childhood B-cell precursor acute lymphoblastic leukemia. Here, the authors show that the DNA editing enzyme AID is expressed in infected B cells but using genetic mouse models show that it does not contribute to leukemia pathogenesis.

    • Guillermo Rodríguez-Hernández
    • , Friederike V. Opitz
    • , Pilar Delgado
    • , Carolin Walter
    • , Ángel F. Álvarez-Prado
    • , Inés González-Herrero
    • , Franziska Auer
    • , Ute Fischer
    • , Stefan Janssen
    • , Christoph Bartenhagen
    • , Javier Raboso-Gallego
    • , Ana Casado-García
    • , Alberto Orfao
    • , Oscar Blanco
    • , Diego Alonso-López
    • , Javier De Las Rivas
    • , Sara González de Tena-Dávila
    • , Markus Müschen
    • , Martin Dugas
    • , Francisco Javier García Criado
    • , María Begoña García Cenador
    • , Carolina Vicente-Dueñas
    • , Julia Hauer
    • , Almudena R. Ramiro
    • , Isidro Sanchez-Garcia
    •  & Arndt Borkhardt
  • 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

    Mutations in LRRK2 and GBA1, which encodes glucocerebrosidase (GCase), are associated with Parkinson’s disease. Here the authors show that LRRK2 is a negative regulator of lysosomal GCase activity, using dopaminergic neurons derived from iPSCs from PD patients with LRRK2 mutations.

    • Daniel Ysselstein
    • , Maria Nguyen
    • , Tiffany J. Young
    • , Alex Severino
    • , Michael Schwake
    • , Kalpana Merchant
    •  & Dimitri Krainc
  • 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

    Climate affects dynamics of infectious diseases, but the impact on respiratory syncytial virus (RSV) epidemiology isn’t well understood. Here, Baker et al. model the influence of temperature, humidity and rainfall on RSV epidemiology in the USA and Mexico and predict impact of climate change on RSV dynamics.

    • Rachel E. Baker
    • , Ayesha S. Mahmud
    • , Caroline E. Wagner
    • , Wenchang Yang
    • , Virginia E. Pitzer
    • , Cecile Viboud
    • , Gabriel A. Vecchi
    • , C. Jessica E. Metcalf
    •  & Bryan T. Grenfell
  • Article
    | Open Access

    Avian influenza A virus (IAV) strains replicate poorly in mammalian hosts, but mechanisms underlying species restriction are incompletely understood. Here, Bogdanow et al. show that avian and mammalian adapted IAV strains have evolved different RNA structure features for regulation of M segment RNA splicing.

    • Boris Bogdanow
    • , Xi Wang
    • , Katrin Eichelbaum
    • , Anne Sadewasser
    • , Immanuel Husic
    • , Katharina Paki
    • , Matthias Budt
    • , Martha Hergeselle
    • , Barbara Vetter
    • , Jingyi Hou
    • , Wei Chen
    • , Lüder Wiebusch
    • , Irmtraud M. Meyer
    • , Thorsten Wolff
    •  & Matthias Selbach
  • Article
    | Open Access

    Urinary tract infections (UTIs) are associated with changes in the gut microbiome. Here, the authors evaluate the relationship between the gut microbiome and development of UTI in kidney transplant patients and show that uropathogenic gut abundance might represent a risk factor for development of bacteriuria and UTI.

    • Matthew Magruder
    • , Adam N. Sholi
    • , Catherine Gong
    • , Lisa Zhang
    • , Emmanuel Edusei
    • , Jennifer Huang
    • , Shady Albakry
    • , Michael J. Satlin
    • , Lars F. Westblade
    • , Carl Crawford
    • , Darshana M. Dadhania
    • , Michelle Lubetzky
    • , Ying Taur
    • , Eric Littman
    • , Lilan Ling
    • , Philip Burnham
    • , Iwijn De Vlaminck
    • , Eric Pamer
    • , Manikkam Suthanthiran
    •  & John Richard Lee
  • 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

    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

    Sequencing cancer genomes reveals low frequency novel somatic variants without known function. Here, the authors leverage statistical methodology from the fields of computational linguistics and ecology to highlight the potentially important signals harboured by these novel variants that are often dismissed.

    • Saptarshi Chakraborty
    • , Arshi Arora
    • , Colin B. Begg
    •  & Ronglai Shen
  • Article
    | Open Access

    In breast cancer, the immune infiltration of the tumour associates with clinical outcome. Here, the authors infer immune context based on gene expression data and identify a new independent subtype linked to pro-tumorigenic immune infiltration.

    • Xavier Tekpli
    • , Tonje Lien
    • , Andreas Hagen Røssevold
    • , Daniel Nebdal
    • , Elin Borgen
    • , Hege Oma Ohnstad
    • , Jon Amund Kyte
    • , Johan Vallon-Christersson
    • , Marie Fongaard
    • , Eldri Undlien Due
    • , Lisa Gregusson Svartdal
    • , My Anh Tu Sveli
    • , Øystein Garred
    • , Anne-Lise Børresen-Dale
    • , Ellen Schlichting
    • , Torill Sauer
    • , Jürgen Geisler
    • , Solveig Hofvind
    • , Tone F. Bathen
    • , Olav Engebråten
    • , Gry Aarum Geitvik
    • , Anita Langerød
    • , Rolf Kåresen
    • , Gunhild Mari Mælandsmo
    • , Ole Christian Lingjærde
    • , Helle Kristine Skjerven
    • , Daehoon Park
    • , Britt Fritzman
    • , Arnoldo Frigessi
    • , Kristine Kleivi Sahlberg
    • , Therese Sørlie
    • , Hege G. Russnes
    • , Bjørn Naume
    •  & Vessela N. Kristensen
  • Article
    | Open Access

    Here, the authors investigate the outcome of prevention services scale-up on HIV incidence in a South African large population-based HIV surveillance cohort with over a decade of follow-up and associate a 43% reduction in incidence to earlier male medical circumcision and increased levels of antiretroviral therapy coverage.

    • Alain Vandormael
    • , Adam Akullian
    • , Mark Siedner
    • , Tulio de Oliveira
    • , Till Bärnighausen
    •  & Frank Tanser
  • Article
    | Open Access

    LRIG1 is a tumour suppressor in several cancers. Here, the authors show that androgen receptor directly transactivates LRIG1 which then antagonises ERBB signalling and c-Myc expression to inhibit prostate tumorigenesis.

    • Qiuhui Li
    • , Bigang Liu
    • , Hsueh-Ping Chao
    • , Yibing Ji
    • , Yue Lu
    • , Rashid Mehmood
    • , Collene Jeter
    • , Taiping Chen
    • , John R. Moore
    • , Wenqian Li
    • , Can Liu
    • , Kiera Rycaj
    • , Amanda Tracz
    • , Jason Kirk
    • , Tammy Calhoun-Davis
    • , Jie Xiong
    • , Qu Deng
    • , Jiaoti Huang
    • , Barbara A. Foster
    • , Abhiram Gokhale
    • , Xin Chen
    •  & Dean G. Tang
  • Article
    | Open Access

    Oncogenic exosomes can circulate in the blood, but their selective removal has not been possible. Here the authors show that aptamer-functionalised mesoporous silica nanoparticles can find to a specific population of circulating exosomes and eliminate them via the hepatobiliary route.

    • Xiaodong Xie
    • , Huifang Nie
    • , Yu Zhou
    • , Shu Lian
    • , Hao Mei
    • , Yusheng Lu
    • , Haiyan Dong
    • , Fengqiao Li
    • , Tao Li
    • , Bifei Li
    • , Jie Wang
    • , Min Lin
    • , Chaihung Wang
    • , Jingwei Shao
    • , Yu Gao
    • , Jianming Chen
    • , Fangwei Xie
    •  & Lee Jia
  • Article
    | Open Access

    Pre-malignant cells harbouring oncogenic mutations can populate and spread throughout a tissue. Here, using a rainbow mouse system, the authors explore how clonal expansion in the mouse intestine might explain high levels of intra-tumoural heterogeneity observed in the disease.

    • Peter G. Boone
    • , Lauren K. Rochelle
    • , Joshua D. Ginzel
    • , Veronica Lubkov
    • , Wendy L. Roberts
    • , P. J. Nicholls
    • , Cheryl Bock
    • , Mei Lang Flowers
    • , Richard J. von Furstenberg
    • , Barry R. Stripp
    • , Pankaj Agarwal
    • , Alexander D. Borowsky
    • , Robert D. Cardiff
    • , Larry S. Barak
    • , Marc G. Caron
    • , H. Kim Lyerly
    •  & Joshua C. Snyder
  • Article
    | Open Access

    Gemcitabine is used to treat gallbaldder cancer but patient responses are variable. Here, the authors use a genome-wide CRISPR screen and identify the translational elongator protein ELP5 as a protein that is important for mediating gemcitabine-induced apoptosis.

    • Sunwang Xu
    • , Ming Zhan
    • , Cen Jiang
    • , Min He
    • , Linhua Yang
    • , Hui Shen
    • , Shuai Huang
    • , Xince Huang
    • , Ruirong Lin
    • , Yongheng Shi
    • , Qiang Liu
    • , Wei Chen
    • , Man Mohan
    •  & Jian Wang
  • Article
    | Open Access

    Higher organisms regulate cellular iron concentrations through Iron Regulatory Proteins (IRPs), which regulate specific messenger RNAs. Here Huynh et al. show that IRP1 requires a Glycogen Branching Enzyme for proper function, and that IRP1 has additional regulatory roles in cell nuclei.

    • Nhan Huynh
    • , Qiuxiang Ou
    • , Pendleton Cox
    • , Roland Lill
    •  & Kirst King-Jones
  • 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

    Histology data exists for many cancer samples and the ability to automatically image this data may provide prognostic information. Here, the authors generated an algorithm to measure tumour infiltrating lymphocytes in melanoma histology specimens and show that the ratio of these immune cells to tumour cells has prognostic value.

    • Balazs Acs
    • , Fahad Shabbir Ahmed
    • , Swati Gupta
    • , Pok Fai Wong
    • , Robyn D. Gartrell
    • , Jaya Sarin Pradhan
    • , Emanuelle M. Rizk
    • , Bonnie Gould Rothberg
    • , Yvonne M. Saenger
    •  & David L. Rimm
  • Article
    | Open Access

    One measurement of tuberculosis vaccine efficacy in clinical trials is prevention of disease, but different mechanisms can underlie disease prevention. Here, the authors develop a mathematical model that allows to identify mechanisms of action of a vaccine preventing TB disease.

    • Mario Tovar
    • , Sergio Arregui
    • , Dessislava Marinova
    • , Carlos Martín
    • , Joaquín Sanz
    •  & Yamir Moreno
  • Article
    | Open Access

    The genomic and immune landscape of pre-invasive lung adenocarcinoma is poorly understood. Here, the authors perform exome and transcriptome sequencing on precursor legions and invasive lung adenocarcinomas, identifying recurrently mutated genes in pre/minimally invasive cases, and arm level alteration events linked to immune infiltration.

    • Haiquan Chen
    • , Jian Carrot-Zhang
    • , Yue Zhao
    • , Haichuan Hu
    • , Samuel S. Freeman
    • , Su Yu
    • , Gavin Ha
    • , Alison M. Taylor
    • , Ashton C. Berger
    • , Lindsay Westlake
    • , Yuanting Zheng
    • , Jiyang Zhang
    • , Aruna Ramachandran
    • , Qiang Zheng
    • , Yunjian Pan
    • , Difan Zheng
    • , Shanbo Zheng
    • , Chao Cheng
    • , Muyu Kuang
    • , Xiaoyan Zhou
    • , Yang Zhang
    • , Hang Li
    • , Ting Ye
    • , Yuan Ma
    • , Zhendong Gao
    • , Xiaoting Tao
    • , Han Han
    • , Jun Shang
    • , Ying Yu
    • , Ding Bao
    • , Yechao Huang
    • , Xiangnan Li
    • , Yawei Zhang
    • , Jiaqing Xiang
    • , Yihua Sun
    • , Yuan Li
    • , Andrew D. Cherniack
    • , Joshua D. Campbell
    • , Leming Shi
    •  & Matthew Meyerson
  • Article
    | Open Access

    Acute Myeloid Leukemia (AML) develops following multiple mutations of differing impact. Here, the authors show that activating mutations of CSF3R co-operate with loss-of-function mutations of CEBPA to promote AML development through an enhancer-dependent mechanism.

    • Theodore P. Braun
    • , Mariam Okhovat
    • , Cody Coblentz
    • , Sarah A. Carratt
    • , Amy Foley
    • , Zachary Schonrock
    • , Brittany M. Smith
    • , Kimberly Nevonen
    • , Brett Davis
    • , Brianna Garcia
    • , Dorian LaTocha
    • , Benjamin R. Weeder
    • , Michal R. Grzadkowski
    • , Joey C. Estabrook
    • , Hannah G. Manning
    • , Kevin Watanabe-Smith
    • , Sophia Jeng
    • , Jenny L. Smith
    • , Amanda R. Leonti
    • , Rhonda E. Ries
    • , Shannon McWeeney
    • , Cristina Di Genua
    • , Roy Drissen
    • , Claus Nerlov
    • , Soheil Meshinchi
    • , Lucia Carbone
    • , Brian J. Druker
    •  & Julia E. Maxson
  • Article
    | Open Access

    Mechanisms of transcription of expanded G4C2 repeats in C9ORF72, associated with ALS/FTD, are not fully understood. Here authors use both Drosophila and C9ORF72 iPSC-derived neurons and identify AFF2/FMR2 as a regulator of poly(GR) toxicity by regulating expression of the expanded G4C2 repeats.

    • Yeliz Yuva-Aydemir
    • , Sandra Almeida
    • , Gopinath Krishnan
    • , Tania F. Gendron
    •  & Fen-Biao Gao