Health sciences

  • 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

    Here, the authors explore the relationship between socioeconomic position (SEP) across the life course and inflammation in a multi-cohort study and show that educational attainment is most strongly related to inflammation, suggesting that socioeconomic disadvantage in young adulthood is independently associated with later life inflammation.

    • Eloïse Berger
    • , Raphaële Castagné
    • , Marc Chadeau-Hyam
    • , Murielle Bochud
    • , Angelo d’Errico
    • , Martina Gandini
    • , Maryam Karimi
    • , Mika Kivimäki
    • , Vittorio Krogh
    • , Michael Marmot
    • , Salvatore Panico
    • , Martin Preisig
    • , Fulvio Ricceri
    • , Carlotta Sacerdote
    • , Andrew Steptoe
    • , Silvia Stringhini
    • , Rosario Tumino
    • , Paolo Vineis
    • , Cyrille Delpierre
    •  & Michelle Kelly-Irving
  • 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

    Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are still unclear. Here the authors show that a SCFA, pentanoate, suppresses autoimmune inflammation in mouse models of colitis and multiple sclerosis via epigenetic modulation of immune cell metabolic and functional pathways.

    • Maik Luu
    • , Sabine Pautz
    • , Vanessa Kohl
    • , Rajeev Singh
    • , Rossana Romero
    • , Sébastien Lucas
    • , Jörg Hofmann
    • , Hartmann Raifer
    • , Niyati Vachharajani
    • , Lucia Campos Carrascosa
    • , Boris Lamp
    • , Andrea Nist
    • , Thorsten Stiewe
    • , Yoav Shaul
    • , Till Adhikary
    • , Mario M. Zaiss
    • , Matthias Lauth
    • , Ulrich Steinhoff
    •  & Alexander Visekruna
  • 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

    Negative selection removes deleterious genetic variation, and can influence genetic architectures and evolution of complex traits. Here, the authors analyze data from 25 UK Biobank diseases and complex traits, and quantify frequency-dependent genetic architectures which suggests actions of negative selection.

    • Armin P. Schoech
    • , Daniel M. Jordan
    • , Po-Ru Loh
    • , Steven Gazal
    • , Luke J. O’Connor
    • , Daniel J. Balick
    • , Pier F. Palamara
    • , Hilary K. Finucane
    • , Shamil R. Sunyaev
    •  & Alkes L. Price
  • 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

    Electroencephalography (EEG) allows the measurement of electrical signals associated with brain activity, but it is unclear if EEG can accurately measure subcortical activity. Here, the authors show that source dynamics, reconstructed from scalp EEG, correlate with activity recorded from human thalamus and nucleus accumbens.

    • Martin Seeber
    • , Lucia-Manuela Cantonas
    • , Mauritius Hoevels
    • , Thibaut Sesia
    • , Veerle Visser-Vandewalle
    •  & Christoph M. Michel
  • Article | | open

    Calcium signalling downstream of VEGF is essential for VEGF-induced angiogenesis. Here Savage et al. show that Transmembrane Protein 33 (TMEM33) is required for angiogenesis and the endothelial calcium response to VEGF, revealing a function for TMEM33 in multicellular organisms.

    • Aaron M. Savage
    • , Sathishkumar Kurusamy
    • , Yan Chen
    • , Zhen Jiang
    • , Karishma Chhabria
    • , Ryan B. MacDonald
    • , Hyejeong R. Kim
    • , Heather L. Wilson
    • , Fredericus J. M. van Eeden
    • , Angel L. Armesilla
    • , Timothy J. A. Chico
    •  & Robert N. Wilkinson
  • 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

    T cells express specific T cell receptors (TCR) to recognise antigens and initiate adaptive immune responses. Here the authors show, in a mouse model of autoimmune encephalomyelitis, that memory-like CD4 T cells expressing unrelated TCR can also infiltrate the spinal cord and contribute to autoimmunity.

    • Hong-Gyun Lee
    • , Jae-Ung Lee
    • , Do-Hyun Kim
    • , Sangho Lim
    • , Insoo Kang
    •  & Je-Min Choi
  • 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

    Ubiquitination may control protein stability or function. Here the authors show that an ubiquitination enzyme, Hectd3, ubiquitinates Stat3 and Malt1 to modulate their function but not degradation in T cells, and thereby promoting the differentiation of pathogenic Th17 cells and susceptibility to a mouse model of multiple sclerosis.

    • Jonathan J. Cho
    • , Zhiwei Xu
    • , Upasana Parthasarathy
    • , Theodore T. Drashansky
    • , Eric Y. Helm
    • , Ashley N. Zuniga
    • , Kyle J. Lorentsen
    • , Samira Mansouri
    • , Joshua Y. Cho
    • , Mariola J. Edelmann
    • , Duc M. Duong
    • , Torben Gehring
    • , Thomas Seeholzer
    • , Daniel Krappmann
    • , Mohammad N. Uddin
    • , Danielle Califano
    • , Rejean L. Wang
    • , Lei Jin
    • , Hongmin Li
    • , Dongwen Lv
    • , Daohong Zhou
    • , Liang Zhou
    •  & Dorina Avram
  • 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

    Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘innateness gradient’ that is associated with changes in proliferation and effector functions.

    • Maria Gutierrez-Arcelus
    • , Nikola Teslovich
    • , Alex R. Mola
    • , Rafael B. Polidoro
    • , Aparna Nathan
    • , Hyun Kim
    • , Susan Hannes
    • , Kamil Slowikowski
    • , Gerald F. M. Watts
    • , Ilya Korsunsky
    • , Michael B. Brenner
    • , Soumya Raychaudhuri
    •  & Patrick J. Brennan
  • 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

    Sex-stratified medicine is an important and understudied field. Here the authors investigate in a systematic study of the Danish population differences in incidence, risk, and several aspects of diagnoses between sexes and find differences across all areas of disease.

    • David Westergaard
    • , Pope Moseley
    • , Freja Karuna Hemmingsen Sørup
    • , Pierre Baldi
    •  & Søren Brunak
  • 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

    Corticosteroids are host-directed drugs that enhance survival of tuberculosis patients through unclear mechanisms. Here, Gräb et al. show that corticosteroids inhibit necrotic death of cells infected with Mycobacterium tuberculosis by facilitating MKP-1-dependent dephosphorylation of p38 MAPK.

    • Jessica Gräb
    • , Isabelle Suárez
    • , Edeltraud van Gumpel
    • , Sandra Winter
    • , Fynn Schreiber
    • , Anna Esser
    • , Christoph Hölscher
    • , Melanie Fritsch
    • , Marc Herb
    • , Michael Schramm
    • , Laurens Wachsmuth
    • , Christian Pallasch
    • , Manolis Pasparakis
    • , Hamid Kashkar
    •  & Jan Rybniker
  • Article | | open

    The diversity of fibroblasts contributing to wound healing is unclear. Here, the authors use single-cell RNA-sequencing to identify heterogeneity among murine fibroblasts in the wound and find that recruited myeloid cells contribute to adipocyte regeneration during healing.

    • Christian F. Guerrero-Juarez
    • , Priya H. Dedhia
    • , Suoqin Jin
    • , Rolando Ruiz-Vega
    • , Dennis Ma
    • , Yuchen Liu
    • , Kosuke Yamaga
    • , Olga Shestova
    • , Denise L. Gay
    • , Zaixin Yang
    • , Kai Kessenbrock
    • , Qing Nie
    • , Warren S. Pear
    • , George Cotsarelis
    •  & Maksim V. Plikus
  • 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

    High-throughput sequencing and analyzes of antibody repertoire provide important information on immune responses, but current methodologies are limited in sequence assembly precision and haplotype inference validity. Here the authors propose a new Bayesian haplotyping method, and attest its broad application with a large, multi-individual dataset.

    • Moriah Gidoni
    • , Omri Snir
    • , Ayelet Peres
    • , Pazit Polak
    • , Ida Lindeman
    • , Ivana Mikocziova
    • , Vikas Kumar Sarna
    • , Knut E. A. Lundin
    • , Christopher Clouser
    • , Francois Vigneault
    • , Andrew M. Collins
    • , Ludvig M. Sollid
    •  & Gur Yaari
  • Article | | open

    The pathways involved in exit from pluripotency in human embryonic stem cells are poorly understood. Here, the authors performed a CRISPR-based screen to identify genes that promote exit from naïve pluripotency and find a role for folliculin (FLCN) by regulating the mTOR and Wnt pathways.

    • J. Mathieu
    • , D. Detraux
    • , D. Kuppers
    • , Y. Wang
    • , C. Cavanaugh
    • , S. Sidhu
    • , S. Levy
    • , A. M. Robitaille
    • , A. Ferreccio
    • , T. Bottorff
    • , A. McAlister
    • , L. Somasundaram
    • , F. Artoni
    • , S. Battle
    • , R. D. Hawkins
    • , R. T. Moon
    • , C. B. Ware
    • , P. J. Paddison
    •  & H. Ruohola-Baker
  • Article | | open

    Diverse interactions between the nervous and immune systems have been shown, but specific mechanistic insights are still lacking. Here the authors show, using both mouse inflammation models and clinical correlation, that adrenergic nerve may ameliorate inflammation by inducing repulsive guidance molecule A signalling.

    • Andreas Körner
    • , Martin Schlegel
    • , Torsten Kaussen
    • , Verena Gudernatsch
    • , Georg Hansmann
    • , Timo Schumacher
    • , Martin Giera
    •  & Valbona Mirakaj
  • 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

    Transplantation of allogeneic bone marrow helps establish chimerism that may induce tolerance to tissue grafts. Here the authors show that a CD117-antibody-drug-conjugate helps precondition the recipients for inducing mixed chimerism and allo-tolerance without clear adverse effects or the need for chronic immune suppression.

    • Zhanzhuo Li
    • , Agnieszka Czechowicz
    • , Amelia Scheck
    • , Derrick J. Rossi
    •  & Philip M. Murphy
  • 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

    The use of pluripotent-stem cell derived organs for transplantation would be promising, if organs can be grown in a suitable host. Here, the authors use interspecific blastocyst complementation to generate a mouse pluripotent stem cell-derived kidney in anephric Sall1 mutant rats.

    • Teppei Goto
    • , Hiromasa Hara
    • , Makoto Sanbo
    • , Hideki Masaki
    • , Hideyuki Sato
    • , Tomoyuki Yamaguchi
    • , Shinichi Hochi
    • , Toshihiro Kobayashi
    • , Hiromitsu Nakauchi
    •  & Masumi Hirabayashi
  • Article | | open

    Host genetics modulates gut microbiota composition, which in turn affects host health, but little is known about the specific genes involved. Here, Berg et al. show that TGFβ/BMP immune signalling affects abundance and function of commensal Enterobacter species in C. elegans.

    • Maureen Berg
    • , David Monnin
    • , Juhyun Cho
    • , Lydia Nelson
    • , Alex Crits-Christoph
    •  & Michael Shapira
  • 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

    Mammalian joints have poor regenerative capacity following amputation. Here, the authors show that in mice, stimulation of the amputation wound with BMP2 and BMP9 stimulates regeneration of a synovial joint that includes bone, cartilage and a synovial cavity.

    • Ling Yu
    • , Lindsay A. Dawson
    • , Mingquan Yan
    • , Katherine Zimmel
    • , Yu-Lieh Lin
    • , Connor P. Dolan
    • , Manjong Han
    •  & Ken Muneoka