Diseases

  • Article | | open

    SIRPa is most commonly known as a phagocytosis inhibitory receptor expressed by myeloid cells. Here the authors show SIRPa is expressed on a subset of CD8+ T cells with higher proliferative and effector activity during the chronic phase of the immune response to viral infection.

    • Lara M. Myers
    • , Michal Caspi Tal
    • , Laughing Bear Torrez Dulgeroff
    • , Aaron B. Carmody
    • , Ronald J. Messer
    • , Gunsagar Gulati
    • , Ying Ying Yiu
    • , Matthew M. Staron
    • , Cesar Lopez Angel
    • , Rahul Sinha
    • , Maxim Markovic
    • , Edward A. Pham
    • , Benjamin Fram
    • , Aijaz Ahmed
    • , Aaron M. Newman
    • , Jeffrey S. Glenn
    • , Mark M. Davis
    • , Susan M. Kaech
    • , Irving L. Weissman
    •  & Kim J. Hasenkrug
  • Article | | open

    Triple negative breast cancers (TNBC) disseminate and metastasise, but the clonal relationship of metastases to primary tumours is poorly understood. Here, the authors use cellular barcoding of TNBC patient-derived xenografts and track the fate of barcoded clones in primary tumours and their metastases, including after resection or chemotherapy.

    • D. Merino
    • , T. S. Weber
    • , A. Serrano
    • , F. Vaillant
    • , K. Liu
    • , B. Pal
    • , L. Di Stefano
    • , J. Schreuder
    • , D. Lin
    • , Y. Chen
    • , M. L. Asselin-Labat
    • , T. N. Schumacher
    • , D. Cameron
    • , G. K. Smyth
    • , A. T. Papenfuss
    • , G. J. Lindeman
    • , J. E. Visvader
    •  & S. H. Naik
  • Article | | open

    FXR1P is a RNA binding protein involved in muscle development. Here, the authors show that mutations in FXR1 exon 15, which is alternatively spliced in muscle, cause multi-minicore myopathy in humans and in mouse models.

    • María Cristina Estañ
    • , Elisa Fernández-Núñez
    • , Maha S. Zaki
    • , María Isabel Esteban
    • , Sandra Donkervoort
    • , Cynthia Hawkins
    • , José A. Caparros-Martin
    • , Dimah Saade
    • , Ying Hu
    • , Véronique Bolduc
    • , Katherine Ru-Yui Chao
    • , Julián Nevado
    • , Ana Lamuedra
    • , Raquel Largo
    • , Gabriel Herrero-Beaumont
    • , Javier Regadera
    • , Concepción Hernandez-Chico
    • , Eduardo F. Tizzano
    • , Victor Martinez-Glez
    • , Jaime J. Carvajal
    • , Ruiting Zong
    • , David L. Nelson
    • , Ghada A. Otaify
    • , Samia Temtamy
    • , Mona Aglan
    • , Mahmoud Issa
    • , Carsten G. Bönnemann
    • , Pablo Lapunzina
    • , Grace Yoon
    •  & Victor L. Ruiz-Perez
  • Article | | open

    Radiomics—the quantification of features within tumor images—has shown prognostic potential in cancer. Here, the authors use a machine learning approach to develop a radiomic-based small set of descriptors to predict ovarian cancer patient survival based on CT scans acquired pre-operatively in 364 patients.

    • Haonan Lu
    • , Mubarik Arshad
    • , Andrew Thornton
    • , Giacomo Avesani
    • , Paula Cunnea
    • , Ed Curry
    • , Fahdi Kanavati
    • , Jack Liang
    • , Katherine Nixon
    • , Sophie T. Williams
    • , Mona Ali Hassan
    • , David D. L. Bowtell
    • , Hani Gabra
    • , Christina Fotopoulou
    • , Andrea Rockall
    •  & Eric O. Aboagye
  • Article | | open

    Infection of a cell with influenza B virus (IBV) often results in cell death and the role of surviving cells in pathogenesis is unclear. Here, Dumm et al. generate a recombinant IBV that activates a host-cell reporter to permanently label infected cells, and show that surviving cells are important to preserve epithelial barrier function.

    • Rebekah E. Dumm
    • , Jessica K. Fiege
    • , Barbara M. Waring
    • , Chay T. Kuo
    • , Ryan A. Langlois
    •  & Nicholas S. Heaton
  • Article | | open

    The fusion peptide (FP) of HIV envelope (Env) is critical in the cell entry process. Here, Kumar et al. present crystal structures of B41 SOSIP.664 Env trimer and show the dynamic nature of the FP and proximal region, which likely relates to conformational rearrangements required for membrane fusion.

    • Sonu Kumar
    • , Anita Sarkar
    • , Pavel Pugach
    • , Rogier W. Sanders
    • , John P. Moore
    • , Andrew B. Ward
    •  & Ian A. Wilson
  • Article | | open

    Phospholipase C β (PLCβ) exhibits immuno-modulatory functions but its role in antiviral innate responses is unclear. Here, the authors provide evidence that PLCβ2 down regulates enterovirus-induced pro-inflammatory responses via inhibition of TAK1 activation, and suggest PLC as a potential therapeutic target.

    • Lin Wang
    • , Yilong Zhou
    • , Zijuan Chen
    • , Lei Sun
    • , Juehui Wu
    • , Haohao Li
    • , Feng Liu
    • , Fei Wang
    • , Chunfu Yang
    • , Juhao Yang
    • , Qibin Leng
    • , Qingli Zhang
    • , Ajing Xu
    • , Lisong Shen
    • , Jinqiao Sun
    • , Dianqing Wu
    • , Caiyun Fang
    • , Haojie Lu
    • , Dapeng Yan
    •  & Baoxue Ge
  • Article | | open

    Whether the Wnt enhanceosome’ components BCL9/9l can affect intestinal homeostasis and tumorigenesis is still unclear. Using conditional Bcl9/9l KO mice, the authors of this study show that the BCL9/9l complex is required for intestinal stem cells to drive tissue regeneration and that loss of BCL9/9l suppresses Wnt-driven transformation.

    • David M. Gay
    • , Rachel A. Ridgway
    • , Miryam Müeller
    • , Michael C. Hodder
    • , Ann Hedley
    • , William Clark
    • , Joshua D. Leach
    • , Rene Jackstadt
    • , Colin Nixon
    • , David J. Huels
    • , Andrew D. Campbell
    • , Thomas G. Bird
    •  & Owen J. Sansom
  • Article | | open

    BCL9 and Pygo are components of Wnt enhanceosome, which facilitates β-catenin-dependent transcription. Here, the authors show that deletion of Bcl9 and Pygo suppresses tumorigenesis and extends disease free survival in two different colorectal cancer models, suggesting a strategy for drugging β-catenin signalling in this cancer.

    • Juliusz Mieszczanek
    • , Laurens M. van Tienen
    • , Ashraf E. K. Ibrahim
    • , Douglas J. Winton
    •  & Mariann Bienz
  • Article | | open

    How HIV reservoirs are shaped over time on antiviral therapy is poorly understood. Here, the authors analyze the dynamics of the HIV reservoir by longitudinal proviral sequencing revealing that HIV reservoir expression can contribute to its clearance and paradoxically even to its persistence.

    • Marilia Rita Pinzone
    • , D. Jake VanBelzen
    • , Sam Weissman
    • , Maria Paola Bertuccio
    • , LaMont Cannon
    • , Emmanuele Venanzi-Rullo
    • , Stephen Migueles
    • , R. Brad Jones
    • , Talia Mota
    • , Sarah B. Joseph
    • , Kevin Groen
    • , Alexander O. Pasternak
    • , Wei-Ting Hwang
    • , Brad Sherman
    • , Anastasios Vourekas
    • , Giuseppe Nunnari
    •  & Una O’Doherty
  • Article | | open

    Targeting histone acetylation modulators (HAMPs) is a promising avenue of drug discovery in cancer research. Here, the authors integrate multi-dimensional genomic profiles to systematically investigate recurrent genomic alterations in HAMPs, identifying potential therapeutic targets for precision epigenetic treatment.

    • Zhongyi Hu
    • , Junzhi Zhou
    • , Junjie Jiang
    • , Jiao Yuan
    • , Youyou Zhang
    • , Xuepeng Wei
    • , Nicki Loo
    • , Yueying Wang
    • , Yutian Pan
    • , Tianli Zhang
    • , Xiaomin Zhong
    • , Meixiao Long
    • , Kathleen T. Montone
    • , Janos L. Tanyi
    • , Yi Fan
    • , Tian-Li Wang
    • , Ie-Ming Shih
    • , Xiaowen Hu
    •  & Lin Zhang
  • Article | | open

    Quaternary contacts mediated by an extended heavy-chain framework region 3 (FR3) have been shown to improve binding to HIV envelope and virus neutralization for a few antibodies. Here, Liu et al. engraft such an FR3 loop onto several potent broadly neutralizing antibodies, resulting in improved neutralization activity and pharmacokinetics.

    • Qingbo Liu
    • , Yen-Ting Lai
    • , Peng Zhang
    • , Mark K. Louder
    • , Amarendra Pegu
    • , Reda Rawi
    • , Mangaiarkarasi Asokan
    • , Xuejun Chen
    • , Chen-Hsiang Shen
    • , Gwo-Yu Chuang
    • , Eun Sung Yang
    • , Huiyi Miao
    • , Yuge Wang
    • , Anthony S. Fauci
    • , Peter D. Kwong
    • , John R. Mascola
    •  & Paolo Lusso
  • Article | | open

    Bladder cancer is one of the most common and highly vascularized cancers. Here the authors perform a whole-genome analysis in urothelial bladder carcinomas and identify recurrent genetic alterations in a set of angiogenesis genes, facilitating the understanding of molecular mechanisms underlying pathological angiogenesis in this type of cancer.

    • Song Wu
    • , Tong Ou
    • , Nianzeng Xing
    • , Jiang Lu
    • , Shengqing Wan
    • , Changxi Wang
    • , Xi Zhang
    • , Feiya Yang
    • , Yi Huang
    •  & Zhiming Cai
  • Article | | open

    Valyl-tRNA synthetase (VARS) charges valyl-tRNA with the amino acid valine, required for translation. Here, the authors describe a progressive epileptic encephalopathy in individuals from five families carrying biallelic mutations in the VARS gene that leave the enzyme activity partially intact.

    • Jennifer Friedman
    • , Desiree E. Smith
    • , Mahmoud Y. Issa
    • , Valentina Stanley
    • , Rengang Wang
    • , Marisa I. Mendes
    • , Meredith S. Wright
    • , Kristen Wigby
    • , Amber Hildreth
    • , John R. Crawford
    • , Alanna E. Koehler
    • , Shimul Chowdhury
    • , Shareef Nahas
    • , Liting Zhai
    • , Zhiwen Xu
    • , Wing-Sze Lo
    • , Kiely N. James
    • , Damir Musaev
    • , Andrea Accogli
    • , Kether Guerrero
    • , Luan T. Tran
    • , Tarek E. I. Omar
    • , Tawfeg Ben-Omran
    • , David Dimmock
    • , Stephen F. Kingsmore
    • , Gajja S. Salomons
    • , Maha S. Zaki
    • , Geneviève Bernard
    •  & Joseph G. Gleeson
  • Article | | open

    Type-2 innate lymphoid cells (ILC2s) are an immune population secreting Th2 cytokines playing a role in the regulation of adipose metabolic homeostasis. Here the authors show that engagement of GITR, a member of the TNF superfamily, in activated ILC2s is protective against insulin resistance in both a preventive and a therapeutic manner in the context of obesity.

    • Lauriane Galle-Treger
    • , Ishwarya Sankaranarayanan
    • , Benjamin P. Hurrell
    • , Emily Howard
    • , Richard Lo
    • , Hadi Maazi
    • , Gavin Lewis
    • , Homayon Banie
    • , Alan L. Epstein
    • , Peisheng Hu
    • , Virender K. Rehan
    • , Frank D. Gilliland
    • , Hooman Allayee
    • , Pejman Soroosh
    • , Arlene H. Sharpe
    •  & Omid Akbari
  • Article | | open

    tRNAs are linked with their cognate amino acid by aminoacyl tRNA synthetases (ARS). Here, the authors report a developmental encephalopathy associated with biallelic VARS variants (valyl-tRNA synthetase) that lead to loss of function, as determined by several in vitro assays and a vars knockout zebrafish model.

    • Aleksandra Siekierska
    • , Hannah Stamberger
    • , Tine Deconinck
    • , Stephanie N. Oprescu
    • , Michèle Partoens
    • , Yifan Zhang
    • , Jo Sourbron
    • , Elias Adriaenssens
    • , Patrick Mullen
    • , Patrick Wiencek
    • , Katia Hardies
    • , Jeong-Soo Lee
    • , Hoi-Khoanh Giong
    • , Felix Distelmaier
    • , Orly Elpeleg
    • , Katherine L. Helbig
    • , Joseph Hersh
    • , Sedat Isikay
    • , Elizabeth Jordan
    • , Ender Karaca
    • , Angela Kecskes
    • , James R. Lupski
    • , Reka Kovacs-Nagy
    • , Patrick May
    • , Vinodh Narayanan
    • , Manuela Pendziwiat
    • , Keri Ramsey
    • , Sampathkumar Rangasamy
    • , Deepali N. Shinde
    • , Ronen Spiegel
    • , Vincent Timmerman
    • , Sarah von Spiczak
    • , Ingo Helbig
    • , Chris Balak
    • , Newell Belnap
    • , Ana Claasen
    • , Amanda Courtright
    • , Matt de Both
    • , Matthew J. Huentelman
    • , Marcus Naymik
    • , Ryan Richholt
    • , Ashley L. Siniard
    • , Szabolcs Szelinger
    • , David W. Craig
    • , Isabelle Schrauwen
    • , Zaid Afawi
    • , Rudi Balling
    • , Stéphanie Baulac
    • , Nina Barišić
    • , Hande S. Caglayan
    • , Dana Craiu
    • , Rosa Guerrero-López
    • , Renzo Guerrini
    • , Helle Hjalgrim
    • , Johanna Jähn
    • , Karl Martin Klein
    • , Eric Leguern
    • , Johannes R. Lemke
    • , Holger Lerche
    • , Carla Marini
    • , Rikke S. Møller
    • , Hiltrud Muhle
    • , Felix Rosenow
    • , Jose Serratosa
    • , Arvid Suls
    • , Ulrich Stephani
    • , Katalin Štěrbová
    • , Pasquale Striano
    • , Federico Zara
    • , Sarah Weckhuysen
    • , Christopher Francklyn
    • , Anthony Antonellis
    • , Peter de Witte
    •  & Peter De Jonghe
  • Article | | open

    Loss of PIK3R1 in ovarian cancer is a common event, which provides opportunities for therapeutic intervention. Here, the authors show that the STAT3 and AKT signaling pathways are activated upon PIK3R1 loss and that, in mice, inhibitors of these pathways could block tumorigenesis.

    • Xinran Li
    • , Victor C. Y. Mak
    • , Yuan Zhou
    • , Chao Wang
    • , Esther S. Y. Wong
    • , Rakesh Sharma
    • , Yiling Lu
    • , Annie N. Y. Cheung
    • , Gordon B. Mills
    •  & Lydia W. T. Cheung
  • Article | | open

    The mechanistic target of rapamycin (TOR) functions as an energy sensor and contributes to the control of glucose homeostasis. Here, the authors show that mTOR in the upper small intestine regulates hepatic glucose production and is required for the glucose lowering effect of metformin.

    • T. M. Zaved Waise
    • , Mozhgan Rasti
    • , Frank A. Duca
    • , Song-Yang Zhang
    • , Paige V. Bauer
    • , Christopher J. Rhodes
    •  & Tony K. T. Lam
  • Article | | open

    The brain primarily uses glucose to generate energy, but the relationship of neuronal activity to glucose utilization is not necessarily a simple linear one. Here, the authors introduce relative power (rPWR) and relative cost (rCST) as new metrics to quantify how brain activity relates to glucose consumption.

    • Ehsan Shokri-Kojori
    • , Dardo Tomasi
    • , Babak Alipanahi
    • , Corinde E. Wiers
    • , Gene-Jack Wang
    •  & Nora D. Volkow
  • Article | | open

    Cancer cells respond differently to inhibitors of Poly (ADP-ribose) polymerase. Here the authors reveal that ovarian cancer cells with higher cellular NADP+ levels are more sensitive to clinically relevant PARP1 inhibitors and show that NADP+ act as an endogenous inhibitor of PARP enzymes.

    • Chunjing Bian
    • , Chao Zhang
    • , Tao Luo
    • , Aditi Vyas
    • , Shih-Hsun Chen
    • , Chao Liu
    • , Muzaffer Ahmad Kassab
    • , Ying Yang
    • , Mei Kong
    •  & Xiaochun Yu
  • Article | | open

    Reduction in food intake elicits neuroendocrine adaptations to counterregulate the negative energy balance, e.g. via reduction in leptin levels. Here, the authors identify an additional starvation signal, growth hormone (GH). Blocking GH receptor attenuates the fall of whole body energy expenditure during food deprivation in mice.

    • Isadora C. Furigo
    • , Pryscila D. S. Teixeira
    • , Gabriel O. de Souza
    • , Gisele C. L. Couto
    • , Guadalupe García Romero
    • , Mario Perelló
    • , Renata Frazão
    • , Lucila L. Elias
    • , Martin Metzger
    • , Edward O. List
    • , John J. Kopchick
    •  & Donato J. Jr
  • Article | | open

    We know a large number of risk SNPs for schizophrenia, but little about how these SNPs contribute to the disorder. Here, the authors use functional genomics to identify risk SNPs that disrupt transcription factor binding and validate the regulatory effects of the transcription factor binding-disrupting SNPs.

    • Yongxia Huo
    • , Shiwu Li
    • , Jiewei Liu
    • , Xiaoyan Li
    •  & Xiong-Jian Luo
  • Article | | open

    When examining the evolution of treatment resistance in breast cancer, perceived genomic changes may be due to clonal evolution or heterogeneous tumors. Here, the authors show that apparent clonal change can in fact be due to pre-treatment heterogeneity, and samples from at least two regions are necessary to detect treatment-induced clonal shifts

    • Jennifer L. Caswell-Jin
    • , Katherine McNamara
    • , Johannes G. Reiter
    • , Ruping Sun
    • , Zheng Hu
    • , Zhicheng Ma
    • , Jie Ding
    • , Carlos J. Suarez
    • , Susanne Tilk
    • , Akshara Raghavendra
    • , Victoria Forte
    • , Suet-Feung Chin
    • , Helen Bardwell
    • , Elena Provenzano
    • , Carlos Caldas
    • , Julie Lang
    • , Robert West
    • , Debu Tripathy
    • , Michael F. Press
    •  & Christina Curtis
  • Article | | open

    MicroRNA miR-500a-5p has been linked to oncogenesis but its role in colorectal cancer (CRC) is largely unknown. Here, the authors investigate the role of miR-500a-5p in CRC in vitro and in vivo models and find that miR-500a-5p acts as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis.

    • Weimei Tang
    • , Weijie Zhou
    • , Li Xiang
    • , Xiaosheng Wu
    • , Pei Zhang
    • , Jing Wang
    • , Guangnan Liu
    • , Wenjing Zhang
    • , Ying Peng
    • , Xiaoting Huang
    • , Jianqun Cai
    • , Yang Bai
    • , Lan Bai
    • , Wei Zhu
    • , Hongxiang Gu
    • , Jing Xiong
    • , Chen Ye
    • , Aimin Li
    • , Side Liu
    •  & Jide Wang
  • Article | | open

    Somatic mutations within antibody framework regions (FWR) can alter structural flexibility, but their role in maturation of broadly neutralizing antibodies (bnAbs) is unclear. Here the authors show how FWR mutations impact interdomain conformational flexibility and paratope plasticity during bnAb development.

    • Rory Henderson
    • , Brian E. Watts
    • , Hieu N. Ergin
    • , Kara Anasti
    • , Robert Parks
    • , Shi-Mao Xia
    • , Ashley Trama
    • , Hua-Xin Liao
    • , Kevin O. Saunders
    • , Mattia Bonsignori
    • , Kevin Wiehe
    • , Barton F. Haynes
    •  & S. Munir Alam
  • Article | | open

    Capicua (CIC) is a tumour suppressor in oligodendroglioma. Here, the authors show that ERK activation mediates CIC regulation via ubiquitination and degradation by PJA1 and a degradation resistant form of CIC enhances efficacy of ERK inhibition in glioblastoma.

    • Severa Bunda
    • , Pardeep Heir
    • , Julie Metcalf
    • , Annie Si Cong Li
    • , Sameer Agnihotri
    • , Stefan Pusch
    • , Mamatjan Yasin
    • , Mira Li
    • , Kelly Burrell
    • , Sheila Mansouri
    • , Olivia Singh
    • , Mark Wilson
    • , Amir Alamsahebpour
    • , Romina Nejad
    • , Bethany Choi
    • , David Kim
    • , Andreas von Deimling
    • , Gelareh Zadeh
    •  & Kenneth Aldape
  • Article | | open

    Insulin-related gene (Insig) negatively regulates hepatic fatty acid synthesis, a process involved in development of non-alcoholic fatty liver disease (NAFLD). Here, the authors show that AMPK activation by metformin promotes Insig phosphorylation, stabilizing it and inhibiting lipogenic gene expression. This is protective against steatosis in diabetic mice.

    • Yamei Han
    • , Zhimin Hu
    • , Aoyuan Cui
    • , Zhengshuai Liu
    • , Fengguang Ma
    • , Yaqian Xue
    • , Yuxiao Liu
    • , Feifei Zhang
    • , Zehua Zhao
    • , Yanyan Yu
    • , Jing Gao
    • , Chun Wei
    • , Jingya Li
    • , Jing Fang
    • , Jia Li
    • , Jian-Gao Fan
    • , Bao-Liang Song
    •  & Yu Li
  • Article | | open

    PTEN is a lipid phosphatase that functions as a dose-dependent tumor suppressor through the PI3K/AKT pathway. Here the authors describe a signaling feedback mechanism where PTEN stability is regulated through transcriptional upregulation of X-linked ubiquitin-specific protease 11 (USP11) via the PI3K/FOXO pathway.

    • Mi Kyung Park
    • , Yixin Yao
    • , Weiya Xia
    • , Stephanie Rebecca Setijono
    • , Jae Hwan Kim
    • , Isabelle K. Vila
    • , Hui-Hsuan Chiu
    • , Yun Wu
    • , Enrique González Billalabeitia
    • , Min Gyu Lee
    • , Robert G. Kalb
    • , Mien-Chie Hung
    • , Pier Paolo Pandolfi
    • , Su Jung Song
    •  & Min Sup Song
  • Article | | open

    Lifestyle factors such as smoking and exercise contribute to the health of the brain during aging, but previous studies have focused on the effects of single lifestyle variables. Here, the authors examine the combined and individual effects of four lifestyle variables on brain structure and function.

    • Nora Bittner
    • , Christiane Jockwitz
    • , Thomas W. Mühleisen
    • , Felix Hoffstaedter
    • , Simon B. Eickhoff
    • , Susanne Moebus
    • , Ute J. Bayen
    • , Sven Cichon
    • , Karl Zilles
    • , Katrin Amunts
    •  & Svenja Caspers
  • Article | | open

    Elevated MYC levels can sensitize tumor cells to apoptosis. In this study, the authors demonstrate that AMPK activation and BCL-2/BCL-XL inhibition have a synergistic effect on apoptosis, and that together with anti PD-1 therapy they can suppress Myc-driven mammary tumor growth.

    • Heidi M. Haikala
    • , Johanna M. Anttila
    • , Elsa Marques
    • , Tiina Raatikainen
    • , Mette Ilander
    • , Henna Hakanen
    • , Hanna Ala-Hongisto
    • , Mariel Savelius
    • , Diego Balboa
    • , Bjoern Von Eyss
    • , Vilja Eskelinen
    • , Pauliina Munne
    • , Anni I. Nieminen
    • , Timo Otonkoski
    • , Julia Schüler
    • , Teemu D. Laajala
    • , Tero Aittokallio
    • , Harri Sihto
    • , Johanna Mattson
    • , Päivi Heikkilä
    • , Marjut Leidenius
    • , Heikki Joensuu
    • , Satu Mustjoki
    • , Panu Kovanen
    • , Martin Eilers
    • , Joel D. Leverson
    •  & Juha Klefström
  • Article | | open

    Nuclear envelopathies are a group of diseases caused by genetic mutations in essential nuclear envelope genes. Here, the authors report a nuclear envelopathy with a homozygous nonsense variant in TOR1AIP1 which leads to changes in the nuclear morphology including large nuclear-spanning channels in patients’ fibroblasts.

    • Boris Fichtman
    • , Fadia Zagairy
    • , Nitzan Biran
    • , Yiftah Barsheshet
    • , Elena Chervinsky
    • , Ziva Ben Neriah
    • , Avraham Shaag
    • , Michael Assa
    • , Orly Elpeleg
    • , Amnon Harel
    •  & Ronen Spiegel
  • Article | | open

    Antibodies against Plasmodium falciparum merozoites that fix complement can inhibit blood-stage replication. Here, Reiling et al. show that complement-fixing antibodies strongly correlate with protective immunity in children, identify the merozoite targets, and predict antigen combinations that should result in strong protection.

    • Linda Reiling
    • , Michelle J. Boyle
    • , Michael T. White
    • , Danny W. Wilson
    • , Gaoqian Feng
    • , Rupert Weaver
    • , D. Herbert Opi
    • , Kristina E. M. Persson
    • , Jack S. Richards
    • , Peter M. Siba
    • , Freya J. I. Fowkes
    • , Eizo Takashima
    • , Takafumi Tsuboi
    • , Ivo Mueller
    •  & James G. Beeson
  • Article | | open

    Non-small cell lung cancers with inactivating SMARCA4 mutations are currently undruggable. Here, the authors show that the absence of SMARCA4/2 reduces chromatin accessibility at the CCND1 locus, leading to a subsequent reduction in cyclin D1 expression, which promotes vulnerability of these cancers to CDK4/6 inhibition.

    • Yibo Xue
    • , Brian Meehan
    • , Zheng Fu
    • , Xue Qing D. Wang
    • , Pierre Olivier Fiset
    • , Ralf Rieker
    • , Cameron Levins
    • , Tim Kong
    • , Xianbing Zhu
    • , Geneviève Morin
    • , Lashanda Skerritt
    • , Esther Herpel
    • , Sriram Venneti
    • , Daniel Martinez
    • , Alexander R. Judkins
    • , Sungmi Jung
    • , Sophie Camilleri-Broet
    • , Anne V. Gonzalez
    • , Marie-Christine Guiot
    • , William W. Lockwood
    • , Jonathan D. Spicer
    • , Abbas Agaimy
    • , William A. Pastor
    • , Josée Dostie
    • , Janusz Rak
    • , William D. Foulkes
    •  & Sidong Huang
  • Article | | open

    Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is driven by SMARCA4 loss. Here the authors demonstrate that SCCOHT cells are highly sensitive to CDK4/6 inhibition and provide mechanistic insights, whereby this druggable vulnerability is driven by cyclin D1 deficiency induced by SMARCA4 loss.

    • Yibo Xue
    • , Brian Meehan
    • , Elizabeth Macdonald
    • , Sriram Venneti
    • , Xue Qing D. Wang
    • , Leora Witkowski
    • , Petar Jelinic
    • , Tim Kong
    • , Daniel Martinez
    • , Geneviève Morin
    • , Michelle Firlit
    • , Atefeh Abedini
    • , Radia M. Johnson
    • , Regina Cencic
    • , Jay Patibandla
    • , Hongbo Chen
    • , Andreas I. Papadakis
    • , Aurelie Auguste
    • , Iris de Rink
    • , Ron M. Kerkhoven
    • , Nicholas Bertos
    • , Walter H. Gotlieb
    • , Blaise A. Clarke
    • , Alexandra Leary
    • , Michael Witcher
    • , Marie-Christine Guiot
    • , Jerry Pelletier
    • , Josée Dostie
    • , Morag Park
    • , Alexander R. Judkins
    • , Ralf Hass
    • , Douglas A. Levine
    • , Janusz Rak
    • , Barbara Vanderhyden
    • , William D. Foulkes
    •  & Sidong Huang
  • Article | | open

    The immunosuppressive tumor environment and the lack of functional anti-tumor immunity are major limiting factors in immunotherapy. Here the authors show that human and mouse tumors are infiltrated by virus-specific memory T cells, which can be harnessed by viral peptides to induce local and systemic anti-tumor immunity and synergize with checkpoint blockade.

    • Pamela C. Rosato
    • , Sathi Wijeyesinghe
    • , J. Michael Stolley
    • , Christine E. Nelson
    • , Rachel L. Davis
    • , Luke S. Manlove
    • , Christopher A. Pennell
    • , Bruce R. Blazar
    • , Clark C. Chen
    • , Melissa A. Geller
    • , Vaiva Vezys
    •  & David Masopust
  • Article | | open

    Midbrain dopamine (mDA) neurons are significantly associated with Parkinson’s disease and yet there is no systematic molecular classification of these heterogenous group of cells. Here authors use single cell RNA sequencing of isolated mouse neurons expressing the transcription factor Pitx3 (broad mDA neuronal marker) to identify and characterize seven neuron subgroups divided in two major branches of developing Pitx3-expressing neurons.

    • Katarína Tiklová
    • , Åsa K. Björklund
    • , Laura Lahti
    • , Alessandro Fiorenzano
    • , Sara Nolbrant
    • , Linda Gillberg
    • , Nikolaos Volakakis
    • , Chika Yokota
    • , Markus M. Hilscher
    • , Thomas Hauling
    • , Fredrik Holmström
    • , Eliza Joodmardi
    • , Mats Nilsson
    • , Malin Parmar
    •  & Thomas Perlmann
  • Article | | open

    The use of sodium-glucose transport protein 2 (SGLT2) inhibitors for the treatment of diabetes has been associated with euglycemic ketoacidosis and increased glucose production and glucagon secretion. Here Perry et al. show that these effects rely on both insulinopenia and dehydration, and thus suggest ways to manage the side effects associated with the use of SGLT2 inhibitors.

    • Rachel J. Perry
    • , Aviva Rabin-Court
    • , Joongyu D. Song
    • , Rebecca L. Cardone
    • , Yongliang Wang
    • , Richard G. Kibbey
    •  & Gerald I. Shulman
  • Article | | open

    CD47 is a promising new target in cancer immunotherapy and recently the pro-phagocytic signal SLAMF7 has been shown to have a crucial role in phagocytosis induced by CD47-blocking antibody in hematological tumors. In this study, the authors demonstrate that SLAMF7 expressed by cancer cells is not required for phagocytosis suggesting that, in contrast to CD47 expression, SLAMF7 should not be used as selection criterion for CD47-targeted therapy.

    • Yuan He
    • , Renee Bouwstra
    • , Valerie R. Wiersma
    • , Mathilde de Jong
    • , Harm Jan Lourens
    • , Rudolf Fehrmann
    • , Marco de Bruyn
    • , Emanuele Ammatuna
    • , Gerwin Huls
    • , Tom van Meerten
    •  & Edwin Bremer
  • Article | | open

    Individuals show large variability in their capacity to lose weight and maintain this weight. Here, the authors perform GWAS in two weight loss intervention cohorts and identify two genetic loci associated with weight loss that are taken forward for Bayesian fine-mapping and functional assessment in flies.

    • Armand Valsesia
    • , Qiao-Ping Wang
    • , Nele Gheldof
    • , Jérôme Carayol
    • , Hélène Ruffieux
    • , Teleri Clark
    • , Victoria Shenton
    • , Lisa J. Oyston
    • , Gregory Lefebvre
    • , Sylviane Metairon
    • , Christian Chabert
    • , Ondine Walter
    • , Polina Mironova
    • , Paulina Lau
    • , Patrick Descombes
    • , Nathalie Viguerie
    • , Dominique Langin
    • , Mary-Ellen Harper
    • , Arne Astrup
    • , Wim H. Saris
    • , Robert Dent
    • , Greg G. Neely
    •  & Jörg Hager
  • Article | | open

    Adeno-associated viral vectors (AAV) are being developed for gene therapy of skeletal muscle, but it is a challenge to achieve robust gene expression. Here, the authors identify muscle-specific cisregulatory elements that lead to a substantial increase in micro-dystrophin and follistatin expression, resulting in a safe and sustainable rescue of the dystrophic phenotype in mouse models.

    • S. Sarcar
    • , W. Tulalamba
    • , M. Y. Rincon
    • , J. Tipanee
    • , H. Q. Pham
    • , H. Evens
    • , D. Boon
    • , E. Samara-Kuko
    • , M. Keyaerts
    • , M. Loperfido
    • , E. Berardi
    • , S. Jarmin
    • , P. In’t Veld
    • , G. Dickson
    • , T. Lahoutte
    • , M. Sampaolesi
    • , P. De Bleser
    • , T. VandenDriessche
    •  & M. K. Chuah
  • Article | | open

    Host-parasite interactions during the exoerythrocytic stage of Plasmodium infection remains poorly understood. Using dual RNA-Seq, the authors show that human mucosal immunity protein mucin-13 is upregulated during Plasmodium hepatic-stage infection and marks infected cells independent of tested Plasmodium species.

    • Gregory M. LaMonte
    • , Pamela Orjuela-Sanchez
    • , Jaeson Calla
    • , Lawrence T. Wang
    • , Shangzhong Li
    • , Justine Swann
    • , Annie N. Cowell
    • , Bing Yu Zou
    • , Alyaa M. Abdel-Haleem Mohamed
    • , Zaira Hellen Villa Galarce
    • , Marta Moreno
    • , Carlos Tong Rios
    • , Joseph M. Vinetz
    • , Nathan Lewis
    •  & Elizabeth A. Winzeler
  • Article | | open

    Metabolic pathways are increasingly recognized as crucial determinants of T cell function. Here the authors show that the balance between IFNγ and IL-10 production in human CD4 T cells is modulated by the cholesterol biosynthetic pathway.

    • Esperanza Perucha
    • , Rossella Melchiotti
    • , Jack A Bibby
    • , Wing Wu
    • , Klaus Stensgaard Frederiksen
    • , Ceri A. Roberts
    • , Zoe Hall
    • , Gaelle LeFriec
    • , Kevin A. Robertson
    • , Paul Lavender
    • , Jens Gammeltoft Gerwien
    • , Leonie S. Taams
    • , Julian L. Griffin
    • , Emanuele de Rinaldis
    • , Lisa G. M. van Baarsen
    • , Claudia Kemper
    • , Peter Ghazal
    •  & Andrew P. Cope
  • Article | | open

    Seasonal malaria chemoprevention provides substantial benefit for young children, but resistance to used drugs will likely develop. Here, Chotsiri et al. evaluate the use of dihydroartemisinin-piperaquine as a regimen in 179 children, and population-based simulations suggest that small children would benefit from a higher and extended dosage.

    • Palang Chotsiri
    • , Issaka Zongo
    • , Paul Milligan
    • , Yves Daniel Compaore
    • , Anyirékun Fabrice Somé
    • , Daniel Chandramohan
    • , Warunee Hanpithakpong
    • , François Nosten
    • , Brian Greenwood
    • , Philip J. Rosenthal
    • , Nicholas J. White
    • , Jean-Bosco Ouédraogo
    •  & Joel Tarning
  • Article | | open

    Organs from donors with transmissible viral infections, such as hepatitis C virus (HCV), are not offered for transplantation due to a high risk of transmission. Here, Galasso et al. develop a method for treatment of HCV-infected human donor lungs that is safe and prevents HCV transmission in the pig model.

    • Marcos Galasso
    • , Jordan J. Feld
    • , Yui Watanabe
    • , Mauricio Pipkin
    • , Cara Summers
    • , Aadil Ali
    • , Robert Qaqish
    • , Manyin Chen
    • , Rafaela V. P. Ribeiro
    • , Khaled Ramadan
    • , Layla Pires
    • , Vanderlei S. Bagnato
    • , Cristina Kurachi
    • , Vera Cherepanov
    • , Gray Moonen
    • , Anajara Gazzalle
    • , Thomas K. Waddell
    • , Mingyao Liu
    • , Shaf Keshavjee
    • , Brian C. Wilson
    • , Atul Humar
    •  & Marcelo Cypel
  • Article | | open

    Blocking the PD-1 pathway was shown to be effective in amyloid beta mouse models, yet little is known about its therapeutic potential in models of tauopathy. The authors show here that blocking PD-L1, a PD-1 ligand, is similarly effective, and that both treatments reversed cognitive deficiencies, and modified disease pathology not only in an animal model of AD, but also in the DM-hTAU mouse tauopathy model, through a mechanism that involves monocyte-derived macrophages.

    • Neta Rosenzweig
    • , Raz Dvir-Szternfeld
    • , Afroditi Tsitsou-Kampeli
    • , Hadas Keren-Shaul
    • , Hila Ben-Yehuda
    • , Pierre Weill-Raynal
    • , Liora Cahalon
    • , Alex Kertser
    • , Kuti Baruch
    • , Ido Amit
    • , Assaf Weiner
    •  & Michal Schwartz
  • Article | | open

    Obesity is associated with altered N-acylethanolamine levels (NAE). Here the authors show that deletion of the gene encoding N-acylphosphatidylethanolamine phospholipase D, a key enzyme for NAE synthesis, in intestinal cells of mice leads to the development of obesity and hepatic steatosis via a mechanism involving the gut-brain axis.

    • Amandine Everard
    • , Hubert Plovier
    • , Marialetizia Rastelli
    • , Matthias Van Hul
    • , Alice de Wouters d’Oplinter
    • , Lucie Geurts
    • , Céline Druart
    • , Sylvie Robine
    • , Nathalie M. Delzenne
    • , Giulio G. Muccioli
    • , Willem M. de Vos
    • , Serge Luquet
    • , Nicolas Flamand
    • , Vincenzo Di Marzo
    •  & Patrice D. Cani
  • Article | | open

    Fibrinogen-like protein 2 (FGL2) mediates immune suppression in glioblastoma (GBM). Here, the authors show that FGL-2 expressed by GBM cancer cells acts by suppressing the differentiation of CD103+ DC cells required to activate the anti-tumor CD8+ T cell response via blocking GM-CSF signalling at NFKB, STAT1/5 and p38 level.

    • Jun Yan
    • , Qingnan Zhao
    • , Konrad Gabrusiewicz
    • , Ling-Yuan Kong
    • , Xueqing Xia
    • , Jian Wang
    • , Martina Ott
    • , Jingda Xu
    • , R. Eric Davis
    • , Longfei Huo
    • , Ganesh Rao
    • , Shao-Cong Sun
    • , Stephanie S. Watowich
    • , Amy B. Heimberger
    •  & Shulin Li
  • Article | | open

    The delivery of single therapeutic microRNAs in brain cancers is challenging. Here, the authors engineer three neuronal microRNAs (miR-124, 128 and 137) into a cluster that, targeting oncogenic chromatin repressors, increases survival of GBM-bearing mice when combined with chemotherapy.

    • Vivek Bhaskaran
    • , Michal O. Nowicki
    • , Mahmoud Idriss
    • , Miguel A. Jimenez
    • , Gianmarco Lugli
    • , Josie L. Hayes
    • , Ahmad Bakur Mahmoud
    • , Rachel E. Zane
    • , Carmela Passaro
    • , Keith L. Ligon
    • , Daphne Haas-Kogan
    • , Agnieszka Bronisz
    • , Jakub Godlewski
    • , Sean E. Lawler
    • , E. Antonio Chiocca
    •  & Pierpaolo Peruzzi