Health sciences

  • 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

    Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

    • David Michalovich
    • , Noelia Rodriguez-Perez
    • , Sylwia Smolinska
    • , Michal Pirozynski
    • , David Mayhew
    • , Sorif Uddin
    • , Stephanie Van Horn
    • , Milena Sokolowska
    • , Can Altunbulakli
    • , Andrzej Eljaszewicz
    • , Benoit Pugin
    • , Weronika Barcik
    • , Magdalena Kurnik-Lucka
    • , Ken A. Saunders
    • , Karen D. Simpson
    • , Peter Schmid-Grendelmeier
    • , Ruth Ferstl
    • , Remo Frei
    • , Noriane Sievi
    • , Malcolm Kohler
    • , Pawel Gajdanowicz
    • , Katrine B. Graversen
    • , Katrine Lindholm Bøgh
    • , Marek Jutel
    • , James R. Brown
    • , Cezmi A. Akdis
    • , Edith M. Hessel
    •  & Liam O’Mahony
  • 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

    The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

    • David M. Barry
    • , Elizabeth A. McMillan
    • , Balvir Kunar
    • , Raphael Lis
    • , Tuo Zhang
    • , Tyler Lu
    • , Edward Daniel
    • , Masataka Yokoyama
    • , Jesus M. Gomez-Salinero
    • , Angara Sureshbabu
    • , Ondine Cleaver
    • , Annarita Di Lorenzo
    • , Mary E. Choi
    • , Jenny Xiang
    • , David Redmond
    • , Sina Y. Rabbany
    • , Thangamani Muthukumar
    •  & Shahin Rafii
  • 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

    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

    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

    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

    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

    Sensory stimuli usually arrive simultaneously but the neural-circuit mechanisms that combine multiple streams of sensory information are incompletely understood. The authors here show that visual-auditory pairing drives plasticity in multi-modal neuron networks within the mouse visual cortex.

    • Thomas Knöpfel
    • , Yann Sweeney
    • , Carola I. Radulescu
    • , Nawal Zabouri
    • , Nazanin Doostdar
    • , Claudia Clopath
    •  & Samuel J. Barnes
  • 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

    Innate immune cells can be trained by some stimuli or pathogen exposures to be metabolically and epigenetically altered such that they have different responses to subsequent exposures. Here the authors show that low-dose LPS trained macrophages and BCG-trained macrophages have opposing effects on fibrosis and inflammation in the context of systemic sclerosis.

    • Mohamed Jeljeli
    • , Luiza Gama Coelho Riccio
    • , Ludivine Doridot
    • , Charlotte Chêne
    • , Carole Nicco
    • , Sandrine Chouzenoux
    • , Quentin Deletang
    • , Yannick Allanore
    • , Niloufar Kavian
    •  & Frédéric Batteux
  • 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

    Attention is known to enhance relevant information in our environment, yet its underlying neural computations remain unclear. Here, the authors provide evidence that the degree to which a neural population can normalize itself results in greater potential for attentional benefits.

    • Ilona M. Bloem
    •  & Sam Ling
  • 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

    Spinal pain is a major clinical problem. Here the authors show that osteoclasts create porous area of endplates of the vertebrae and sensory innervation of porous endplates by Netrin-1 release from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice.

    • Shuangfei Ni
    • , Zemin Ling
    • , Xiao Wang
    • , Yong Cao
    • , Tianding Wu
    • , Ruoxian Deng
    • , Janet L. Crane
    • , Richard Skolask
    • , Shadpour Demehril
    • , Gehua Zhen
    • , Amit Jain
    • , Panfeng Wu
    • , Dayu Pan
    • , Bo Hu
    • , Xiao Lyu
    • , Yusheng Li
    • , Hao Chen
    • , Huabin Qi
    • , Yun Guan
    • , Xinzhong Dong
    • , Mei Wan
    • , Xuenong Zou
    • , Hongbin Lu
    • , Jianzhong Hu
    •  & Xu Cao
  • 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

    Here, Nelson et al. use amplicon next-generation sequencing of two P. falciparum polymorphic gene regions to investigate the genetic similarity of parasite populations across time and space in a pediatric cohort in Kenya. They identify both micro- and macro-scale structuring of malaria parasites in this high-transmission setting, which could inform future intervention strategies.

    • Cody S. Nelson
    • , Kelsey M. Sumner
    • , Elizabeth Freedman
    • , Joseph W. Saelens
    • , Andrew A. Obala
    • , Judith N. Mangeni
    • , Steve M. Taylor
    •  & Wendy P. O’Meara
  • 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

    The visual word form area (VWFA) is a brain region associated with written language, but it has also been linked to visuospatial attention. Here, the authors reveal distinct structural and functional circuits linking VWFA with language and attention networks, and demonstrate that these circuits separately predict language and attention abilities.

    • Lang Chen
    • , Demian Wassermann
    • , Daniel A. Abrams
    • , John Kochalka
    • , Guillermo Gallardo-Diez
    •  & Vinod Menon
  • Article
    | Open Access

    Olfactory bulb neurogenesis raises the question of how persistent olfactory memories are retained while remaining flexible to encode new memories. Here, the authors show that new neurons can only support a single odor memory within their critical period of integration into the circuit.

    • Jérémy Forest
    • , Mélissa Moreno
    • , Matthias Cavelius
    • , Laura Chalençon
    • , Anne Ziessel
    • , Joëlle Sacquet
    • , Marion Richard
    • , Anne Didier
    •  & Nathalie Mandairon
  • 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

    Trypanosoma brucei relies on uptake and conversion of purines from the host, which constitutes a potential drug target. Here, Hulpia et al. combine structural elements from known trypanocidal nucleoside analogues and develop a potent trypanocide with curative activity in animal models of acute and late stage sleeping sickness.

    • Fabian Hulpia
    • , Dorien Mabille
    • , Gustavo D. Campagnaro
    • , Gabriela Schumann
    • , Louis Maes
    • , Isabel Roditi
    • , Anders Hofer
    • , Harry P. de Koning
    • , Guy Caljon
    •  & Serge Van Calenbergh
  • 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

    Help from CD4+ T cells is important to induce CD8+ T cell memory responses, but mechanistic insights are lacking. Here, the authors show, by transcriptomics and epigenetics, how CD4+ T cells help program memory CD8+ T cells for help-independent recall by antigens, as well as for innate-like recall responses by IL-12/IL-18 and promoting survival by IL-15.

    • Tomasz Ahrends
    • , Julia Busselaar
    • , Tesa M. Severson
    • , Nikolina Bąbała
    • , Evert de Vries
    • , Astrid Bovens
    • , Lodewyk Wessels
    • , Fred van Leeuwen
    •  & Jannie Borst
  • 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