Diseases

  • Article
    | Open Access

    In Parkinson’s disease (PD) the monomeric protein alpha-synuclein (aSyn) misfolds and aggregates into insoluble fibrils. Here the authors use NMR measurements and hydrogen–deuterium exchange mass spectrometry and find that the more solvent exposed the N-terminus of aSyn is, the more aggregation prone its conformation becomes, and further show how PD mutations and post translational modifications influence the extent of the N-terminus solvent exposure.

    • Amberley D. Stephens
    • , Maria Zacharopoulou
    • , Rani Moons
    • , Giuliana Fusco
    • , Neeleema Seetaloo
    • , Anass Chiki
    • , Philippa J. Woodhams
    • , Ioanna Mela
    • , Hilal A. Lashuel
    • , Jonathan J. Phillips
    • , Alfonso De Simone
    • , Frank Sobott
    •  & Gabriele S. Kaminski Schierle
  • Article
    | Open Access

    Anorexia nervosa is an eating disorder characterized by fear of gaining weight that can lead to serious complications. Here the authors show that inhibition of SIRT1 is protective against the onset and progression of anorectic behavior in an activity-based anorexia model, suggesting SIRT1 could be a potential therapeutic target.

    • Timothy M. Robinette
    • , Justin W. Nicholatos
    • , Adam B. Francisco
    • , Kayla E. Brooks
    • , Rachel Y. Diao
    • , Sandro Sorbi
    • , Valdo Ricca
    • , Benedetta Nacmias
    • , Miguel A. Brieño-Enríquez
    •  & Sergiy Libert
  • Article
    | Open Access

    Uropathogenic E. coli can adhere to vaginal epithelial cells preceding urinary tract infection (UTI). Here, Brannon et al. show that urinary E. coli isolates can not only adhere to, but also invade vaginal cells in mouse UTI models and in clinical samples obtained from women with recurrent UTI.

    • John R. Brannon
    • , Taryn L. Dunigan
    • , Connor J. Beebout
    • , Tamia Ross
    • , Michelle A. Wiebe
    • , William S. Reynolds
    •  & Maria Hadjifrangiskou
  • Article
    | Open Access

    Fibroblast contributions to lung fibrosis and in particular their crosstalk with immune cells in the lung are incompletely understood. Here, the authors show an overall immune suppressive environment transcriptionally controlled and maintained by fibroblasts in lung fibrosis with possible therapeutic implications.

    • Lu Cui
    • , Shih-Yu Chen
    • , Tristan Lerbs
    • , Jin-Wook Lee
    • , Pablo Domizi
    • , Sydney Gordon
    • , Yong-hun Kim
    • , Garry Nolan
    • , Paola Betancur
    •  & Gerlinde Wernig
  • Article
    | Open Access

    Mutations that affect Treg cell function can cause lethal autoimmunity, but whether correcting these mutations can reverse established disease is unclear. Here, the authors correct Treg cell-specific Brg1 mutation in a minor fraction of Treg cells, which supercharges these cells to rescue mice from otherwise fatal IPEX-like autoimmunity.

    • Yongqin Li
    • , Yuxin Chen
    • , Shaoshuai Mao
    • , Ravinder Kaundal
    • , Zhengyu Jing
    • , Qin Chen
    • , Xinxin Wang
    • , Jing Xia
    • , Dahai Liu
    • , Jianlong Sun
    • , Haopeng Wang
    •  & Tian Chi
  • Article
    | Open Access

    Oxidative stress is involved in several diseases and is a target for intervention. Here, the authors report on the synthesis of ultrasmall copper-based nanozymes as reactive oxygen species scavengers and demonstrate improved treatment outcomes in acute liver and kidney injury and wound healing in vivo.

    • Tengfei Liu
    • , Bowen Xiao
    • , Fei Xiang
    • , Jianglin Tan
    • , Zhuo Chen
    • , Xiaorong Zhang
    • , Chengzhou Wu
    • , Zhengwei Mao
    • , Gaoxing Luo
    • , Xiaoyuan Chen
    •  & Jun Deng
  • Article
    | Open Access

    Here, the authors implement a mathematical model that describes how Baloxavir antiviral-induced inhibition of influenza virus replication in infected individuals affects the spread of the virus during epidemics, suggesting that both the scaling up and acceleration of treatment would avert substantial influenza morbidity and mortality every year.

    • Zhanwei Du
    • , Ciara Nugent
    • , Alison P. Galvani
    • , Robert M. Krug
    •  & Lauren Ancel Meyers
  • Article
    | Open Access

    Alport syndrome is a progressive inherited nephritis accompanied by sensorineural loss of hearing and ocular abnormalities, for which there is currently no effective therapy. Here, the authors develop an exon-skipping therapy using an antisense-oligonucleotide and show it is effective in mouse models.

    • Tomohiko Yamamura
    • , Tomoko Horinouchi
    • , Tomomi Adachi
    • , Maki Terakawa
    • , Yutaka Takaoka
    • , Kohei Omachi
    • , Minoru Takasato
    • , Kiyosumi Takaishi
    • , Takao Shoji
    • , Yoshiyuki Onishi
    • , Yoshito Kanazawa
    • , Makoto Koizumi
    • , Yasuko Tomono
    • , Aki Sugano
    • , Akemi Shono
    • , Shogo Minamikawa
    • , China Nagano
    • , Nana Sakakibara
    • , Shinya Ishiko
    • , Yuya Aoto
    • , Misato Kamura
    • , Yutaka Harita
    • , Kenichiro Miura
    • , Shoichiro Kanda
    • , Naoya Morisada
    • , Rini Rossanti
    • , Ming Juan Ye
    • , Yoshimi Nozu
    • , Masafumi Matsuo
    • , Hirofumi Kai
    • , Kazumoto Iijima
    •  & Kandai Nozu
  • Article
    | Open Access

    The common ABCG2 variant Q141K contributes to hyperuricemia and gout risk. Here, using a human interventional study and a new orthologous mouse model, the authors report a tissue specific pathobiology of the Q141K variant, and support a significant role for ABCG2 in urate excretion in both the kidney and intestine.

    • Kazi Mirajul Hoque
    • , Eryn E. Dixon
    • , Raychel M. Lewis
    • , Jordyn Allan
    • , Gregory D. Gamble
    • , Amanda J. Phipps-Green
    • , Victoria L. Halperin Kuhns
    • , Anne M. Horne
    • , Lisa K. Stamp
    • , Tony R. Merriman
    • , Nicola Dalbeth
    •  & Owen M. Woodward
  • Article
    | Open Access

    Fragile X Mental Retardation Protein regulates synaptic plasticity and its loss results in Fragile X Syndrome. Here, the authors show that the FMRP(1-297)-tat peptide can permeate the BBB, restore protein translation and mossy fiber LTP, and reduce elevated levels of activity in Fmr1 KO mice.

    • Xiaoqin Zhan
    • , Hadhimulya Asmara
    • , Ning Cheng
    • , Giriraj Sahu
    • , Eduardo Sanchez
    • , Fang-Xiong Zhang
    • , Gerald W. Zamponi
    • , Jong M. Rho
    •  & Ray W. Turner
  • Article
    | Open Access

    Nebulin-based nemaline myopathy is a heterogenous disease with unclear pathological mechanisms. Here, the authors generate a mouse model that mimics the most common genetic cause of the disease and demonstrate that muscle weakness in this model is associated with twisted actin filaments and altered tropomyosin and troponin behaviour.

    • Johan Lindqvist
    • , Weikang Ma
    • , Frank Li
    • , Yaeren Hernandez
    • , Justin Kolb
    • , Balazs Kiss
    • , Paola Tonino
    • , Robbert van der Pijl
    • , Esmat Karimi
    • , Henry Gong
    • , Josh Strom
    • , Zaynab Hourani
    • , John E. Smith III
    • , Coen Ottenheijm
    • , Thomas Irving
    •  & Henk Granzier
  • Article
    | Open Access

    Injury of corpus cavernosa results in erectile dysfunction, and repair leading to restoration of function is difficult. Here the authors construct 3D printed hydrogel constructs seeded with HIF-1α-expressing muscle derived stem cells to restore corpus function in a rabbit model.

    • Geng An
    • , Feixiang Guo
    • , Xuemin Liu
    • , Zhifang Wang
    • , Ye Zhu
    • , Yong Fan
    • , Chengkai Xuan
    • , Yan Li
    • , Hongkai Wu
    • , Xuetao Shi
    •  & Chuanbin Mao
  • Article
    | Open Access

    Drugs for filariases are under development and clinical trial simulators could help to inform the design of clinical trials. Here, Walker et al. use an individual-based onchocerciasis transmission model to project trial outcomes of a hypothetical macrofilaricidal drug, resolving key design choices.

    • Martin Walker
    • , Jonathan I. D. Hamley
    • , Philip Milton
    • , Frédéric Monnot
    • , Belén Pedrique
    •  & Maria-Gloria Basáñez
  • Article
    | Open Access

    Whole-genome sequencing (WGS) can support drug resistance surveillance, but is rare in low- and middle-income countries. Here, the authors integrate WGS within the national antimicrobial resistance surveillance program in the Philippines and conduct a retrospective sequencing survey to characterize bacterial populations and dissect resistance phenotypes.

    • Silvia Argimón
    • , Melissa A. L. Masim
    • , June M. Gayeta
    • , Marietta L. Lagrada
    • , Polle K. V. Macaranas
    • , Victoria Cohen
    • , Marilyn T. Limas
    • , Holly O. Espiritu
    • , Janziel C. Palarca
    • , Jeremiah Chilam
    • , Manuel C. Jamoralin Jr.
    • , Alfred S. Villamin
    • , Janice B. Borlasa
    • , Agnettah M. Olorosa
    • , Lara F. T. Hernandez
    • , Karis D. Boehme
    • , Benjamin Jeffrey
    • , Khalil Abudahab
    • , Charmian M. Hufano
    • , Sonia B. Sia
    • , John Stelling
    • , Matthew T. G. Holden
    • , David M. Aanensen
    •  & Celia C. Carlos
  • Article
    | Open Access

    α-Syn in CSF is a biomarker of neurodegenerative diseases; however, the detection of clinically relevant species is difficult. Here, the authors create a nanobody biosensor that reveals the presence of α-Syn in cells, which allow the detection of transmittable forms of α-Syn present in human CSF.

    • Christoph Gerdes
    • , Natalia Waal
    • , Thomas Offner
    • , Eugenio F. Fornasiero
    • , Nora Wender
    • , Hannes Verbarg
    • , Ivan Manzini
    • , Claudia Trenkwalder
    • , Brit Mollenhauer
    • , Timo Strohäker
    • , Markus Zweckstetter
    • , Stefan Becker
    • , Silvio O. Rizzoli
    • , Fitnat Buket Basmanav
    •  & Felipe Opazo
  • Article
    | Open Access

    Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. Here, the authors show that microglia-specific deletion of TSPO and chemical inhibition of TSPO prevent neuroinflammation and vascular damage in a mouse model of AMD.

    • Anne Wolf
    • , Marc Herb
    • , Michael Schramm
    •  & Thomas Langmann
  • Article
    | Open Access

    Here, the authors sample air and surfaces in hospital rooms of COVID-19 patients, detect SARS-CoV-2 RNA in air samples of two of three tested airborne infection isolation rooms, and find surface contamination in 66.7% of tested rooms during the first week of illness and 20% beyond the first week of illness.

    • Po Ying Chia
    • , Kristen Kelli Coleman
    • , Yian Kim Tan
    • , Sean Wei Xiang Ong
    • , Marcus Gum
    • , Sok Kiang Lau
    • , Xiao Fang Lim
    • , Ai Sim Lim
    • , Stephanie Sutjipto
    • , Pei Hua Lee
    • , Than The Son
    • , Barnaby Edward Young
    • , Donald K. Milton
    • , Gregory C. Gray
    • , Stephan Schuster
    • , Timothy Barkham
    • , Partha Pratim De
    • , Shawn Vasoo
    • , Monica Chan
    • , Brenda Sze Peng Ang
    • , Boon Huan Tan
    • , Yee-Sin Leo
    • , Oon-Tek Ng
    • , Michelle Su Yen Wong
    • , Kalisvar Marimuthu
    • , David Chien Lye
    • , Poh Lian Lim
    • , Cheng Chuan Lee
    • , Li Min Ling
    • , Lawrence Lee
    • , Tau Hong Lee
    • , Chen Seong Wong
    • , Sapna Sadarangani
    • , Ray Junhao Lin
    • , Deborah Hee Ling Ng
    • , Mucheli Sadasiv
    • , Tsin Wen Yeo
    • , Chiaw Yee Choy
    • , Glorijoy Shi En Tan
    • , Frederico Dimatatac
    • , Isais Florante Santos
    • , Chi Jong Go
    • , Yu Kit Chan
    • , Jun Yang Tay
    • , Jackie Yu-Ling Tan
    • , Nihar Pandit
    • , Benjamin Choon Heng Ho
    • , Shehara Mendis
    • , Yuan Yi Constance Chen
    • , Mohammad Yazid Abdad
    •  & Daniela Moses
  • Article
    | Open Access

    Sensory hypersensitivity is common in autism spectrum disorders. Using functional MRI, psychophysics, and computational modeling, Schallmo et al. show that differences in visual motion perception in ASD are accompanied by weaker neural suppression in visual cortex.

    • Michael-Paul Schallmo
    • , Tamar Kolodny
    • , Alexander M. Kale
    • , Rachel Millin
    • , Anastasia V. Flevaris
    • , Richard A. E. Edden
    • , Jennifer Gerdts
    • , Raphael A. Bernier
    •  & Scott O. Murray
  • Article
    | Open Access

    The relationship between histopathology, gene expression, and biochemical and mechanical properties of wounds is largely unknown. Here, the authors show that activin A alters wound healing at multiple levels by promoting pro-fibrotic gene expression and matrix deposition, thereby affecting biomechanical properties of skin wounds.

    • Mateusz S. Wietecha
    • , Marco Pensalfini
    • , Michael Cangkrama
    • , Bettina Müller
    • , Juyoung Jin
    • , Jürgen Brinckmann
    • , Edoardo Mazza
    •  & Sabine Werner
  • Article
    | Open Access

    Semantic dementia patients present with a core semantic impairment and variations of language, behavioural and face recognition abilities. Here, the authors build a unified multidimensional model to capture all these graded symptoms and map them to the variations in the patients’ frontotemporal atrophy.

    • Junhua Ding
    • , Keliang Chen
    • , Haoming Liu
    • , Lin Huang
    • , Yan Chen
    • , Yingru Lv
    • , Qing Yang
    • , Qihao Guo
    • , Zaizhu Han
    •  & Matthew. A. Lambon Ralph
  • Article
    | Open Access

    Current machine learning classifiers have been applied to whole-genome sequencing data to identify determinants of antimicrobial resistance, but they lack interpretability. Here the authors present a metabolic machine learning classifier that uses flux balance analysis to estimate the biochemical effects of alleles.

    • Erol S. Kavvas
    • , Laurence Yang
    • , Jonathan M. Monk
    • , David Heckmann
    •  & Bernhard O. Palsson
  • Article
    | Open Access

    During the progression of type 2 diabetes, insulin-producing β-cells can lose their identity and become reprogrammed into other cell types. Here the authors show that murine diabetic β-cells require the protein Raptor for maintaining β-cell health and preventing them from turning into α-cells, independent of Raptor’s involvement in regulating blood sugar levels.

    • Qinglei Yin
    • , Qicheng Ni
    • , Yichen Wang
    • , Hongli Zhang
    • , Wenyi Li
    • , Aifang Nie
    • , Shu Wang
    • , Yanyun Gu
    • , Qidi Wang
    •  & Guang Ning
  • Article
    | Open Access

    Here, the authors report the results of a randomized, placebo controlled trial of children with acute gastroenteritis who were treated with a probiotic and find no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or clearance of viral nucleic acid from stool specimens.

    • Stephen B. Freedman
    • , Jianling Xie
    • , Alberto Nettel-Aguirre
    • , Xiao-Li Pang
    • , Linda Chui
    • , Sarah Williamson-Urquhart
    • , David Schnadower
    • , Suzanne Schuh
    • , Philip M. Sherman
    • , Bonita E. Lee
    • , Serge Gouin
    • , Ken J. Farion
    • , Naveen Poonai
    • , Katrina F. Hurley
    • , Yuanyuan Qiu
    • , Binal Ghandi
    • , Colin Lloyd
    • , Yaron Finkelstein
    • , Stephen B. Freedman
    • , Jianling Xie
    • , Alberto Nettel-Aguirre
    • , Xiao-Li Pang
    • , Linda Chui
    • , Sarah Williamson-Urquhart
    • , David Schnadower
    • , Suzanne Schuh
    • , Philip M. Sherman
    • , Bonita Lee
    • , Serge Gouin
    • , Ken J. Farion
    • , Naveen Poonai
    • , Katrina F. Hurley
    • , Yuanyuan Qiu
    • , Binal Ghandi
    • , Colin Lloyd
    • , Yaron Finkelstein
    • , Andrew R. Willan
    • , Ron Goeree
    • , David W. Johnson
    • , Karen Black
    •  & Marc H. Gorelick
  • Article
    | Open Access

    Influenza A virus (IAV) infection can be exacerbated by bacterial co-infections but the effect of IAV on the upper respiratory tract (URT) microbiome remains unclear. Here, the authors compare the dynamics of the UTR microbiome in IAV-infected ferrets and humans, finding similar trends at the ecosystem and individual taxon level in both hosts.

    • Drishti Kaul
    • , Raveen Rathnasinghe
    • , Marcela Ferres
    • , Gene S. Tan
    • , Aldo Barrera
    • , Brett E. Pickett
    • , Barbara A. Methe
    • , Suman Das
    • , Isolda Budnik
    • , Rebecca A. Halpin
    • , David Wentworth
    • , Mirco Schmolke
    • , Ignacio Mena
    • , Randy A. Albrecht
    • , Indresh Singh
    • , Karen E. Nelson
    • , Adolfo García-Sastre
    • , Chris L. Dupont
    •  & Rafael A. Medina
  • Article
    | Open Access

    Potential changes in the seasonality of temperature-attributable mortality due to climate warming have been poorly investigated. Here, the authors show that the projected decrease in the number of moderate and extreme cold days will not contribute to a further reduction of cold-attributable deaths.

    • Hicham Achebak
    • , Daniel Devolder
    • , Vijendra Ingole
    •  & Joan Ballester
  • Article
    | Open Access

    Chronic pain usually induces anxiety. Here, the authors report that vmPFC nNOS-expressing neurons are activated by excitatory inputs from pPVT during chronic pain and subsequently induce anxiety-like behaviors in mice through promoting AMPAR trafficking.

    • Hai-Ying Liang
    • , Zhi-Jin Chen
    • , Hui Xiao
    • , Yu-Hui Lin
    • , Ying-Yi Hu
    • , Lei Chang
    • , Hai-Yin Wu
    • , Peng Wang
    • , Wei Lu
    • , Dong-Ya Zhu
    •  & Chun-Xia Luo
  • Article
    | Open Access

    Following ischemic insult, neovascularization and vascular remodelling play an essential part in the repair of brain damage. Here the authors show that neutrophil extracellular traps serve a detrimental role in the regeneration process, limiting the functional recovery of the brain post injury.

    • Lijing Kang
    • , Huilin Yu
    • , Xing Yang
    • , Yuanbo Zhu
    • , Xiaofei Bai
    • , Ranran Wang
    • , Yongliang Cao
    • , Haochen Xu
    • , Haiyu Luo
    • , Lu Lu
    • , Mei-Juan Shi
    • , Yujing Tian
    • , Wenying Fan
    •  & Bing-Qiao Zhao
  • Article
    | Open Access

    Sterol O-acyltransferase 1 (SOAT1, also named ACAT1) is an endoplasmic reticulum resident enzyme which catalyzes the esterification of cholesterol to generate cholesteryl esters. Here, authors report cryo-EM structures of human SOAT1 which reveal the binding site of the competitive inhibitor CI-976.

    • Chengcheng Guan
    • , Yange Niu
    • , Si-Cong Chen
    • , Yunlu Kang
    • , Jing-Xiang Wu
    • , Koji Nishi
    • , Catherine C. Y. Chang
    • , Ta-Yuan Chang
    • , Tuoping Luo
    •  & Lei Chen
  • Article
    | Open Access

    There are no reliable tests for placental insufficiency, which can lead to fetal growth restriction and stillbirth. Here the authors demonstrate that low levels of circulating SPINT1 are associated to low birthweight, and several ultrasound and neonatal anthropomorphic indicators of placental insufficiency.

    • Tu’uhevaha J. Kaitu’u-Lino
    • , Teresa M. MacDonald
    • , Ping Cannon
    • , Tuong-Vi Nguyen
    • , Richard J. Hiscock
    • , Nick Haan
    • , Jenny E. Myers
    • , Roxanne Hastie
    • , Kirsten M. Dane
    • , Anna L. Middleton
    • , Intissar Bittar
    • , Amanda N. Sferruzzi-Perri
    • , Natasha Pritchard
    • , Alesia Harper
    • , Natalie J. Hannan
    • , Valerie Kyritsis
    • , Nick Crinis
    • , Lisa Hui
    • , Susan P. Walker
    •  & Stephen Tong
  • Article
    | Open Access

    Obesity is a global pandemic with limited treatment options. Here, the authors show evidence in mice that the mitochondrial uncoupler BAM15 effectively induces fat loss without affecting food intake or compromising lean body mass.

    • Stephanie J. Alexopoulos
    • , Sing-Young Chen
    • , Amanda E. Brandon
    • , Joseph M. Salamoun
    • , Frances L. Byrne
    • , Christopher J. Garcia
    • , Martina Beretta
    • , Ellen M. Olzomer
    • , Divya P. Shah
    • , Ashleigh M. Philp
    • , Stefan R. Hargett
    • , Robert T. Lawrence
    • , Brendan Lee
    • , James Sligar
    • , Pascal Carrive
    • , Simon P. Tucker
    • , Andrew Philp
    • , Carolin Lackner
    • , Nigel Turner
    • , Gregory J. Cooney
    • , Webster L. Santos
    •  & Kyle L. Hoehn
  • Article
    | Open Access

    Progressive fibrosis is a driver of morbidity and mortality in many chronic liver diseases, but the underlying mechanisms are incompletely understood. Here, the authors show that mitochondria-derived damage-associated molecular patterns are released from injured hepatocytes and can trigger fibrogenic activation of hepatic stellate cells.

    • Ping An
    • , Lin-Lin Wei
    • , Shuangshuang Zhao
    • , Deanna Y. Sverdlov
    • , Kahini A. Vaid
    • , Makoto Miyamoto
    • , Kaori Kuramitsu
    • , Michelle Lai
    •  & Yury V. Popov
  • Article
    | Open Access

    Fasting diets are emerging as an approach to delay tumor progression and improve cancer therapies. Here, the authors show that the combination of fasting-mimicking diet with vitamin C decreases tumor development and increases chemotherapy efficacy in KRAS-mutant cancer.

    • Maira Di Tano
    • , Franca Raucci
    • , Claudio Vernieri
    • , Irene Caffa
    • , Roberta Buono
    • , Maura Fanti
    • , Sebastian Brandhorst
    • , Giuseppe Curigliano
    • , Alessio Nencioni
    • , Filippo de Braud
    •  & Valter D. Longo
  • Article
    | Open Access

    Recombinant T-cells receptors can redirect naïve T cells but often have low or uneven expression. Here, the authors model mutations in TCR constant domains to increase T cell receptor expression, assembly, and stability and generate bispecific molecules.

    • Karen Froning
    • , Jack Maguire
    • , Arlene Sereno
    • , Flora Huang
    • , Shawn Chang
    • , Kenneth Weichert
    • , Anton J. Frommelt
    • , Jessica Dong
    • , Xiufeng Wu
    • , Heather Austin
    • , Elaine M. Conner
    • , Jonathan R. Fitchett
    • , Aik Roy Heng
    • , Deepa Balasubramaniam
    • , Mark T. Hilgers
    • , Brian Kuhlman
    •  & Stephen J. Demarest
  • Article
    | Open Access

    Depression is correlated with many brain-related traits. Here, Shen et al. perform phenome-wide association studies of a depression polygenic risk score (PRS) and find associations with 51 behavioural and 26 neuroimaging traits which are further followed up on using Mendelian randomization and mediation analyses.

    • Xueyi Shen
    • , David M. Howard
    • , Mark J. Adams
    • , W. David Hill
    • , Toni-Kim Clarke
    • , Mark J. Adams
    • , Toni-Kim Clarke
    • , Andrew M. McIntosh
    • , Ian J. Deary
    • , Naomi R. Wray
    • , Stephan Ripke
    • , Manuel Mattheisen
    • , Maciej Trzaskowski
    • , Enda M. Byrne
    • , Abdel Abdellaoui
    • , Esben Agerbo
    • , Tracy M. Air
    • , Till F. M. Andlauer
    • , Silviu-Alin Bacanu
    • , Marie Bækvad-Hansen
    • , Aartjan T. F. Beekman
    • , Tim B. Bigdeli
    • , Elisabeth B. Binder
    • , Julien Bryois
    • , Henriette N. Buttenschøn
    • , Jonas Bybjerg-Grauholm
    • , Na Cai
    • , Enrique Castelao
    • , Jane Hvarregaard Christensen
    • , Jonathan R. I. Coleman
    • , Lucía Colodro-Conde
    • , Baptiste Couvy-Duchesne
    • , Nick Craddock
    • , Gregory E. Crawford
    • , Gail Davies
    • , Franziska Degenhardt
    • , Eske M. Derks
    • , Nese Direk
    • , Conor V. Dolan
    • , Erin C. Dunn
    • , Thalia C. Eley
    • , Valentina Escott-Price
    • , Farnush Farhadi Hassan Kiadeh
    • , Hilary K. Finucane
    • , Jerome C. Foo
    • , Andreas J. Forstner
    • , Josef Frank
    • , Héléna A. Gaspar
    • , Michael Gill
    • , Fernando S. Goes
    • , Scott D. Gordon
    • , Jakob Grove
    • , Lynsey S. Hall
    • , Christine Søholm Hansen
    • , Thomas F. Hansen
    • , Stefan Herms
    • , Ian B. Hickie
    • , Per Hoffmann
    • , Georg Homuth
    • , Carsten Horn
    • , Jouke-Jan Hottenga
    • , David M. Hougaard
    • , David M. Howard
    • , Marcus Ising
    • , Rick Jansen
    • , Ian Jones
    • , Lisa A. Jones
    • , Eric Jorgenson
    • , James A. Knowles
    • , Isaac S. Kohane
    • , Julia Kraft
    • , Warren W. Kretzschmar
    • , Zoltán Kutalik
    • , Yihan Li
    • , Penelope A. Lind
    • , Donald J. MacIntyre
    • , Dean F. MacKinnon
    • , Robert M. Maier
    • , Wolfgang Maier
    • , Jonathan Marchini
    • , Hamdi Mbarek
    • , Patrick McGrath
    • , Peter McGuffin
    • , Sarah E. Medland
    • , Divya Mehta
    • , Christel M. Middeldorp
    • , Evelin Mihailov
    • , Yuri Milaneschi
    • , Lili Milani
    • , Francis M. Mondimore
    • , Grant W. Montgomery
    • , Sara Mostafavi
    • , Niamh Mullins
    • , Matthias Nauck
    • , Bernard Ng
    • , Michel G. Nivard
    • , Dale R. Nyholt
    • , Paul F. O’Reilly
    • , Hogni Oskarsson
    • , Michael J. Owen
    • , Jodie N. Painter
    • , Carsten Bøcker Pedersen
    • , Marianne Giørtz Pedersen
    • , Roseann E. Peterson
    • , Erik Pettersson
    • , Wouter J. Peyrot
    • , Giorgio Pistis
    • , Danielle Posthuma
    • , Jorge A. Quiroz
    • , Per Qvist
    • , John P. Rice
    • , Brien P. Riley
    • , Margarita Rivera
    • , Saira Saeed Mirza
    • , Robert Schoevers
    • , Eva C. Schulte
    • , Ling Shen
    • , Jianxin Shi
    • , Stanley I. Shyn
    • , Engilbert Sigurdsson
    • , Grant C. B. Sinnamon
    • , Johannes H. Smit
    • , Daniel J. Smith
    • , Hreinn Stefansson
    • , Stacy Steinberg
    • , Fabian Streit
    • , Jana Strohmaier
    • , Katherine E. Tansey
    • , Henning Teismann
    • , Alexander Teumer
    • , Wesley Thompson
    • , Pippa A. Thomson
    • , Thorgeir E. Thorgeirsson
    • , Matthew Traylor
    • , Jens Treutlein
    • , Vassily Trubetskoy
    • , Andrés G. Uitterlinden
    • , Daniel Umbricht
    • , Sandra Van der Auwera
    • , Albert M. van Hemert
    • , Alexander Viktorin
    • , Peter M. Visscher
    • , Yunpeng Wang
    • , Bradley T. Webb
    • , Shantel Marie Weinsheimer
    • , Jürgen Wellmann
    • , Gonneke Willemsen
    • , Stephanie H. Witt
    • , Yang Wu
    • , Hualin S. Xi
    • , Jian Yang
    • , Futao Zhang
    • , Volker Arolt
    • , Bernhard T. Baune
    • , Klaus Berger
    • , Dorret I. Boomsma
    • , Sven Cichon
    • , Udo Dannlowski
    • , E. J. C. de Geus
    • , J. Raymond DePaulo
    • , Enrico Domenici
    • , Katharina Domschke
    • , Tõnu Esko
    • , Hans J. Grabe
    • , Steven P. Hamilton
    • , Caroline Hayward
    • , Andrew C. Heath
    • , Kenneth S. Kendler
    • , Stefan Kloiber
    • , Glyn Lewis
    • , Qingqin S. Li
    • , Susanne Lucae
    • , Pamela A. F. Madden
    • , Patrik K. Magnusson
    • , Nicholas G. Martin
    • , Andres Metspalu
    • , Ole Mors
    • , Preben Bo Mortensen
    • , Bertram Müller-Myhsok
    • , Merete Nordentoft
    • , Markus M. Nöthen
    • , Michael C. O’Donovan
    • , Sara A. Paciga
    • , Nancy L. Pedersen
    • , Brenda W. J. H. Penninx
    • , Roy H. Perlis
    • , David J. Porteous
    • , James B. Potash
    • , Martin Preisig
    • , Marcella Rietschel
    • , Catherine Schaefer
    • , Thomas G. Schulze
    • , Jordan W. Smoller
    • , Kari Stefansson
    • , Henning Tiemeier
    • , Rudolf Uher
    • , Henry Völzke
    • , Myrna M. Weissman
    • , Thomas Werge
    • , Cathryn M. Lewis
    • , Douglas F. Levinson
    • , Gerome Breen
    • , Anders D. Børglum
    • , Patrick F. Sullivan
    • , Ian J. Deary
    • , Heather C. Whalley
    •  & Andrew M. McIntosh
  • Article
    | Open Access

    Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1α. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1α induction.

    • Katrin Fischer
    • , Anna Fenzl
    • , Dianxin Liu
    • , Kenneth A. Dyar
    • , Maximilian Kleinert
    • , Markus Brielmeier
    • , Christoffer Clemmensen
    • , Anna Fedl
    • , Brian Finan
    • , Andre Gessner
    • , Martin Jastroch
    • , Jianfeng Huang
    • , Susanne Keipert
    • , Martin Klingenspor
    • , Jens C. Brüning
    • , Manfred Kneilling
    • , Florian C. Maier
    • , Ahmed E. Othman
    • , Bernd J. Pichler
    • , Ines Pramme-Steinwachs
    • , Stephan Sachs
    • , Angelika Scheideler
    • , Wolfgang M. Thaiss
    • , Henriette Uhlenhaut
    • , Siegfried Ussar
    • , Stephen C. Woods
    • , Julia Zorn
    • , Kerstin Stemmer
    • , Sheila Collins
    • , Maria Diaz-Meco
    • , Jorge Moscat
    • , Matthias H. Tschöp
    •  & Timo D. Müller
  • Article
    | Open Access

    Adipose tissue expansion occurs via enlargement of adipocytes as well as the generation of new fat cells, the latter being associated with more favorable metabolic outcomes. Here, the authors show that activation of adipocyte Piezo1 results in release of FGF1 and stimulates the differentiation of adipocyte precursor cells.

    • ShengPeng Wang
    • , Shuang Cao
    • , Malika Arhatte
    • , Dahui Li
    • , Yue Shi
    • , Sabrina Kurz
    • , Jiong Hu
    • , Lei Wang
    • , Jingchen Shao
    • , Ann Atzberger
    • , Zheng Wang
    • , Changhe Wang
    • , Weijin Zang
    • , Ingrid Fleming
    • , Nina Wettschureck
    • , Eric Honoré
    •  & Stefan Offermanns
  • Article
    | Open Access

    Runx2 is essential for tuning the generation of bone from skeletal stem cells (SSCs). Here, the authors demonstrate that the CK2/HAUSP pathway stabilizes RUNX2 protein thereby regulating the commitment of SSCs to osteoprogenitors as well as their subsequent maturation, and that inhibition of this pathway can block heterotopic ossification.

    • Jung-Min Kim
    • , Yeon-Suk Yang
    • , Kwang Hwan Park
    • , Xianpeng Ge
    • , Ren Xu
    • , Na Li
    • , Minkyung Song
    • , Hyunho Chun
    • , Seoyeon Bok
    • , Julia F. Charles
    • , Odile Filhol-Cochet
    • , Brigitte Boldyreff
    • , Teresa Dinter
    • , Paul B. Yu
    • , Ning Kon
    • , Wei Gu
    • , Takeshi Takarada
    • , Matthew B. Greenblatt
    •  & Jae-Hyuck Shim
  • Article
    | Open Access

    Chronic graft versus host disease (cGvHD) is a major cause of morbidity and mortality in allogeneic bone marrow transplantation. Here the authors identify a recurrent activating mTOR mutation in expanded donor T-cell clones of 3 cGvHD patients, which suggests somatic mutations may contribute to GvHD pathogenesis and opens avenues to targeted therapies.

    • Daehong Kim
    • , Giljun Park
    • , Jani Huuhtanen
    • , Sofie Lundgren
    • , Rajiv K. Khajuria
    • , Ana M. Hurtado
    • , Cecilia Muñoz-Calleja
    • , Laura Cardeñoso
    • , Valle Gómez-García de Soria
    • , Tzu Hua Chen-Liang
    • , Samuli Eldfors
    • , Pekka Ellonen
    • , Sari Hannula
    • , Matti Kankainen
    • , Oscar Bruck
    • , Anna Kreutzman
    • , Urpu Salmenniemi
    • , Tapio Lönnberg
    • , Andrés Jerez
    • , Maija Itälä-Remes
    • , Mikko Myllymäki
    • , Mikko A. I. Keränen
    •  & Satu Mustjoki
  • Article
    | Open Access

    Infiltration of immune cells to the pancreatic islets precedes clinical symptoms of type 1 diabetes, and lack of methods to detect this insulitis impedes early interventions. Here the authors report a contrast enhanced ultrasound method that can detect early insulitis in mouse models of type 1 diabetes, based on increased microvascular permeability.

    • David G. Ramirez
    • , Eric Abenojar
    • , Christopher Hernandez
    • , David S. Lorberbaum
    • , Lucine A. Papazian
    • , Samantha Passman
    • , Vinh Pham
    • , Agata A. Exner
    •  & Richard K. P. Benninger
  • Article
    | Open Access

    Mircobial symbionts of mosquitoes can affect transmission of human pathogens. Here, Herren et al. identify a microsporidian symbiont in Anopheles gambiae that impairs transmission without affecting mosquito fecundity or survival.

    • Jeremy K. Herren
    • , Lilian Mbaisi
    • , Enock Mararo
    • , Edward E. Makhulu
    • , Victor A. Mobegi
    • , Hellen Butungi
    • , Maria Vittoria Mancini
    • , Joseph W. Oundo
    • , Evan T. Teal
    • , Silvain Pinaud
    • , Mara K. N. Lawniczak
    • , Jordan Jabara
    • , Godfrey Nattoh
    •  & Steven P. Sinkins
  • Article
    | Open Access

    RNA viruses can be detected by immune cell pattern recognition receptors, such as RLRs, resulting in MAVS-TBK1-IRF3 signalling and production of antiviral type 1 interferons. Here the authors show that macrophage TRAF3-interacting protein 3 regulates this signalling pathway by interacting with TRAF3 and TBK1 to suppress interferon responses.

    • Meng Deng
    • , Jason W. Tam
    • , Lufei Wang
    • , Kaixin Liang
    • , Sirui Li
    • , Lu Zhang
    • , Haitao Guo
    • , Xiaobo Luo
    • , Yang Zhang
    • , Alex Petrucelli
    • , Beckley K. Davis
    • , Brian J. Conti
    • , W. June Brickey
    • , Ching-Chang Ko
    • , Yu L. Lei
    • , Shaocong Sun
    •  & Jenny P. -Y. Ting
  • Article
    | Open Access

    Molecular mechanisms linking myocardial insulin resistance to diabetic cardiomyopathy are incompletely understood. Here the authors show that myocardial insulin resistance impairs a PKB-SPEG-SERCA2a signaling axis, which contributes to the development of diabetic cardiomyopathy.

    • Chao Quan
    • , Qian Du
    • , Min Li
    • , Ruizhen Wang
    • , Qian Ouyang
    • , Shu Su
    • , Sangsang Zhu
    • , Qiaoli Chen
    • , Yang Sheng
    • , Liang Chen
    • , Hong Wang
    • , David G. Campbell
    • , Carol MacKintosh
    • , Zhongzhou Yang
    • , Kunfu Ouyang
    • , Hong Yu Wang
    •  & Shuai Chen
  • Article
    | Open Access

    Developing noninvasive diagnostic biomarkers for lupus nephritis (LN) diagnosis is an important clinical goal. Here the authors identify urinary proteins correlated with active LN and disease severity, which differ across ethnicities but collectively outperform the current clinical method.

    • Samantha Stanley
    • , Kamala Vanarsa
    • , Samar Soliman
    • , Deena Habazi
    • , Claudia Pedroza
    • , Gabriel Gidley
    • , Ting Zhang
    • , Shree Mohan
    • , Evan Der
    • , Hemant Suryawanshi
    • , Thomas Tuschl
    • , Jill Buyon
    • , Chaim Putterman
    • , Chi Chiu Mok
    • , Michelle Petri
    • , Ramesh Saxena
    •  & Chandra Mohan
  • Article
    | Open Access

    The mechanisms underlying cardiac inflammation in diabetic cardiomyopathy are incompletely understood. Here the authors show that advanced glycation end products bind to the TLR4 co-receptor MD2 initiating pro-inflammatory pathways.

    • Yi Wang
    • , Wu Luo
    • , Jibo Han
    • , Zia A. Khan
    • , Qilu Fang
    • , Yiyi Jin
    • , Xuemei Chen
    • , Yali Zhang
    • , Meihong Wang
    • , Jianchang Qian
    • , Weijian Huang
    • , Hazel Lum
    • , Gaojun Wu
    •  & Guang Liang
  • Article
    | Open Access

    The genome of the malaria parasite Plasmodium falciparum contains a record of past evolutionary forces. Here, using 2537 parasite sequences from the Democratic Republic of the Congo, the authors demonstrate how drug pressure and human movement have shaped the present-day parasite population.

    • Robert Verity
    • , Ozkan Aydemir
    • , Nicholas F. Brazeau
    • , Oliver J. Watson
    • , Nicholas J. Hathaway
    • , Melchior Kashamuka Mwandagalirwa
    • , Patrick W. Marsh
    • , Kyaw Thwai
    • , Travis Fulton
    • , Madeline Denton
    • , Andrew P. Morgan
    • , Jonathan B. Parr
    • , Patrick K. Tumwebaze
    • , Melissa Conrad
    • , Philip J. Rosenthal
    • , Deus S. Ishengoma
    • , Jeremiah Ngondi
    • , Julie Gutman
    • , Modest Mulenga
    • , Douglas E. Norris
    • , William J. Moss
    • , Benedicta A. Mensah
    • , James L. Myers-Hansen
    • , Anita Ghansah
    • , Antoinette K. Tshefu
    • , Azra C. Ghani
    • , Steven R. Meshnick
    • , Jeffrey A. Bailey
    •  & Jonathan J. Juliano
  • Article
    | Open Access

    Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications with limited treatment options. Here the authors show that dysregulation of bile acids increases risk for PTB in pregnant women while restoring bile acid homeostasis delays or prevents PTB in the mouse models.

    • Sangmin You
    • , Ai-Min Cui
    • , Syed F. Hashmi
    • , Xinmu Zhang
    • , Christina Nadolny
    • , Yuan Chen
    • , Qiwen Chen
    • , Xin Bush
    • , Zachary Hurd
    • , Winifer Ali
    • , Gang Qin
    •  & Ruitang Deng
  • Article
    | Open Access

    The blood–cerebrospinal fluid barrier (BCSFB) is an important interface for brain homeostasis. Here the authors describe a non-invasive MRI technique for the quantitative assessment of BCSFB function.

    • P. G. Evans
    • , M. Sokolska
    • , A. Alves
    • , I. F. Harrison
    • , Y. Ohene
    • , P. Nahavandi
    • , O. Ismail
    • , E. Miranda
    • , M. F. Lythgoe
    • , D. L. Thomas
    •  & J. A. Wells
  • Article
    | Open Access

    SARS-CoV-2 uses ACE2 as the entry receptor. Here, the authors show that an ACE2-Ig fusion protein inhibits entry of virus pseudotyped with the SARS-CoV-2 spike protein, show differential binding kinetics of SARS-CoV and SARSCoV-2 spike proteins to ACE2, and determine pharmakocinetic parameters of ACE2-Ig in mice.

    • Changhai Lei
    • , Kewen Qian
    • , Tian Li
    • , Sheng Zhang
    • , Wenyan Fu
    • , Min Ding
    •  & Shi Hu
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Here, the authors show that deficiency of the E3 ubiqutin-protein ligase Nedd4-2 in airway epithelial cells causes IPF-like disease in adult mice. This model may aid studies of the pathogenesis and therapy of IPF.

    • Julia Duerr
    • , Dominik H. W. Leitz
    • , Magdalena Szczygiel
    • , Dmytro Dvornikov
    • , Simon G. Fraumann
    • , Clemens Kreutz
    • , Piotr K. Zadora
    • , Ayça Seyhan Agircan
    • , Philip Konietzke
    • , Theresa A. Engelmann
    • , Jan Hegermann
    • , Surafel Mulugeta
    • , Hiroshi Kawabe
    • , Lars Knudsen
    • , Matthias Ochs
    • , Daniela Rotin
    • , Thomas Muley
    • , Michael Kreuter
    • , Felix J. F. Herth
    • , Mark O. Wielpütz
    • , Michael F. Beers
    • , Ursula Klingmüller
    •  & Marcus A. Mall