Health sciences

  • 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

    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

    Focal adhesion kinase (FAK) is required for tumour angiogenesis and growth. Here, the authors show that deletion of pericyte FAK upregulates Gas6-Axl mediated Cyr61 production, which increases endothelial cell proliferation and angiogenesis, while elevating tissue factor production to enhance tumour cell proliferation.

    • Tanguy Lechertier
    • , Louise E. Reynolds
    • , Hyojin Kim
    • , Ana Rita Pedrosa
    • , Jesús Gómez-Escudero
    • , José M. Muñoz-Félix
    • , Silvia Batista
    • , Matthew Dukinfield
    • , Fevzi Demircioglu
    • , Ping Pui Wong
    • , Kylie P. Matchett
    • , Neil C. Henderson
    • , Gabriela D’Amico
    • , Maddy Parsons
    • , Catherine Harwood
    • , Pascal Meier
    •  & Kairbaan M. Hodivala-Dilke
  • 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

    The location and extent of intranasal oxytocin brain penetrance has not been shown. Here the authors show that oxytocin, administered intranasally, enters brain regions along the trajectories of the olfactory and trigeminal nerves and there, reaches biologically relevant concentrations.

    • M. R. Lee
    • , T. A. Shnitko
    • , S. W. Blue
    • , A. V. Kaucher
    • , A. J. Winchell
    • , D. W. Erikson
    • , K. A. Grant
    •  & L. Leggio
  • 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

    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

    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

    New anti-fibrotics aided by a better understanding of fibrotic cell subsets and their functions are needed. Here the authors perform single-cell RNA-seq and CyTOF on nodules from patients with Dupuytren’s disease to map subsets and the state of mesenchymal cells during pathogenic fibrogenesis.

    • Thomas B. Layton
    • , Lynn Williams
    • , Fiona McCann
    • , Mingjun Zhang
    • , Marco Fritszche
    • , Huw Colin-York
    • , Marisa Cabrita
    • , Michael T. H. Ng
    • , Marc Feldmann
    • , Stephen Samson
    • , Dominic Furniss
    • , Weilin Xie
    •  & Jagdeep Nanchahal
  • Article
    | Open Access

    Human norovirus pathogenesis is incompletely understood due to a lack of appropriate animal disease models. Here, Green et al. show norovirus replication in chromogranin A-positive enteroendocrine cells and other epithelial cells in tissue from a pediatric intestinal transplant recipient with severe gastroenteritis.

    • Kim Y. Green
    • , Stuart S. Kaufman
    • , Bianca M. Nagata
    • , Natthawan Chaimongkol
    • , Daniel Y. Kim
    • , Eric A. Levenson
    • , Christine M. Tin
    • , Allison Behrle Yardley
    • , Jordan A. Johnson
    • , Ana Beatriz F. Barletta
    • , Khalid M. Khan
    • , Nada A. Yazigi
    • , Sukanya Subramanian
    • , Sangeetha R. Moturi
    • , Thomas M. Fishbein
    • , Ian N. Moore
    •  & Stanislav V. Sosnovtsev
  • Article
    | Open Access

    Study of human heart failure is limited by access to human tissue. Here, the authors apply multi-omic screening in human ischaemic and dilated myocardial tissue and matched controls to determine molecular changes common and unique to each aetiology and to reveal differences between male and female hearts.

    • Mengbo Li
    • , Benjamin L. Parker
    • , Evangeline Pearson
    • , Benjamin Hunter
    • , Jacob Cao
    • , Yen Chin Koay
    • , Oneka Guneratne
    • , David E. James
    • , Jean Yang
    • , Sean Lal
    •  & John F. O’Sullivan
  • 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

    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

    Castration resistant prostate cancer patients treated with enzalutamide may develop resistance to the drug. Here, the authors report that monoamine oxidase-A expression is increased in these resistant tumors and that the antidepressants phenelzine/clorgyline can reverse such resistance to further suppress tumor growth

    • Keliang Wang
    • , Jie Luo
    • , Shuyuan Yeh
    • , Bosen You
    • , Jialin Meng
    • , Philip Chang
    • , Yuanjie Niu
    • , Gonghui Li
    • , Changxue Lu
    • , Yezi Zhu
    • , Emmanuel S. Antonarakis
    • , Jun Luo
    • , Chi-Ping Huang
    • , Wanhai Xu
    •  & Chawnshang Chang
  • 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

    Here the authors perform a gain-of-function screen and identify CDKN2C as a host factor for HBV replication, inducing cell cycle arrest and expression of HBV transcription enhancers. CDKN2C expression correlates with disease progression suggesting a potential role in HBV-induced liver disease.

    • Carla Eller
    • , Laura Heydmann
    • , Che C. Colpitts
    • , Houssein El Saghire
    • , Federica Piccioni
    • , Frank Jühling
    • , Karim Majzoub
    • , Caroline Pons
    • , Charlotte Bach
    • , Julie Lucifora
    • , Joachim Lupberger
    • , Michael Nassal
    • , Glenn S. Cowley
    • , Naoto Fujiwara
    • , Sen-Yung Hsieh
    • , Yujin Hoshida
    • , Emanuele Felli
    • , Patrick Pessaux
    • , Camille Sureau
    • , Catherine Schuster
    • , David E. Root
    • , Eloi R. Verrier
    •  & Thomas F. Baumert
  • Article
    | Open Access

    ARID1A, which is often mutated in human endometrial cancer, is a component of the SWI/SNF chromatin remodelling complex. Here, the authors show that Arid1a mutations in the mouse endometrium and primary human endometrial epithelial cells cause widespread reprogramming of gene transcription and result in a loss of response to TGFβ.

    • Yohan Suryo Rahmanto
    • , Wenjing Shen
    • , Xu Shi
    • , Xi Chen
    • , Yu Yu
    • , Zheng-Cheng Yu
    • , Tsutomu Miyamoto
    • , Meng-Horng Lee
    • , Vivek Singh
    • , Ryoichi Asaka
    • , Geoffrey Shimberg
    • , Michele I. Vitolo
    • , Stuart S. Martin
    • , Denis Wirtz
    • , Ronny Drapkin
    • , Jianhua Xuan
    • , Tian-Li Wang
    •  & Ie-Ming Shih
  • 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

    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

    Obesity and type 2 diabetes (T2D) are metabolic disorders characterized by insulin resistance in skeletal muscle. Here, the authors map skeletal muscle enhancer elements dynamically regulated after exposure to free fatty acid palmitate or inflammatory cytokine TNFα and identify target genes involved in metabolic dysfunction in skeletal muscle.

    • Kristine Williams
    • , Lars R. Ingerslev
    • , Jette Bork-Jensen
    • , Martin Wohlwend
    • , Ann Normann Hansen
    • , Lewin Small
    • , Rasmus Ribel-Madsen
    • , Arne Astrup
    • , Oluf Pedersen
    • , Johan Auwerx
    • , Christopher T. Workman
    • , Niels Grarup
    • , Torben Hansen
    •  & Romain Barrès
  • Article
    | Open Access

    Milk breastfeeding and prebiotic-supplemented formulas have varying effects on the infant gut microbiome. Here, in a randomized controlled clinical trial, the authors investigate the effects of a Lactobacillus paracasei-fermented formula on the immune defense mechanisms, microbiota and its metabolome in full term infants.

    • Paola Roggero
    • , Nadia Liotto
    • , Chiara Pozzi
    • , Daniele Braga
    • , Jacopo Troisi
    • , Camilla Menis
    • , Maria Lorella Giannì
    • , Roberto Berni Canani
    • , Lorella Paparo
    • , Rita Nocerino
    • , Andrea Budelli
    • , Fabio Mosca
    •  & Maria Rescigno
  • 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

    Defects in homologous recombination (HR) are found in some triple negative breast cancers, suggesting they may be sensitive to PARP inhibitors. In this phase II clinical trial of the PARP inhibitor rucaparib, changes in Ki67 levels did not correlate with markers of HR deficiency but HR deficiency was detected in 69% of tumours, indicating that PARP inhibitors may be a useful treatment.

    • Neha Chopra
    • , Holly Tovey
    • , Alex Pearson
    • , Ros Cutts
    • , Christy Toms
    • , Paula Proszek
    • , Michael Hubank
    • , Mitch Dowsett
    • , Andrew Dodson
    • , Frances Daley
    • , Divya Kriplani
    • , Heidi Gevensleben
    • , Helen Ruth Davies
    • , Andrea Degasperi
    • , Rebecca Roylance
    • , Stephen Chan
    • , Andrew Tutt
    • , Anthony Skene
    • , Abigail Evans
    • , Judith M. Bliss
    • , Serena Nik-Zainal
    •  & Nicholas C. Turner
  • Article
    | Open Access

    Mutations in the TRPV4 channel cause inherited neurodegeneration syndromes, but the molecular mechanisms are unknown. Here the authors reveal that TRPV4 activation causes dose-dependent, CaMKII-mediated neuronal dysfunction and axonal degeneration via disruption of mitochondrial axonal transport.

    • Brian M. Woolums
    • , Brett A. McCray
    • , Hyun Sung
    • , Masashi Tabuchi
    • , Jeremy M. Sullivan
    • , Kendra Takle Ruppell
    • , Yunpeng Yang
    • , Catherine Mamah
    • , William H. Aisenberg
    • , Pamela C. Saavedra-Rivera
    • , Bryan S. Larin
    • , Alexander R. Lau
    • , Douglas N. Robinson
    • , Yang Xiang
    • , Mark N. Wu
    • , Charlotte J. Sumner
    •  & Thomas E. Lloyd
  • Article
    | Open Access

    Adrenal aldosterone production is regulated by plasma angiotensin and potassium levels. Here the authors report that the neuropeptide substance P stimulates aldosterone production via neurokinin type 1 receptors (NK1R), and report a proof-of-concept placebo controlled clinical trial showing that a NK1R antagonist decreases aldosterone levels.

    • Julien Wils
    • , Céline Duparc
    • , Anne-Françoise Cailleux
    • , Antoine-Guy Lopez
    • , Caroline Guiheneuf
    • , Isabelle Boutelet
    • , Hadrien-Gaël Boyer
    • , Christophe Dubessy
    • , Saloua Cherifi
    • , Bruno Cauliez
    • , Françoise Gobet
    • , Guillaume Defortescu
    • , Jean-François Ménard
    • , Estelle Louiset
    •  & Hervé Lefebvre
  • 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

    Gut microbiome has been linked to cavernous angioma (CA), a common vascular disease, but the role in humans remains unclear. Here, the authors combine 16S rRNA sequencing and shotgun metagenomics to profile the microbiome in a large cohort of human subjects with and without CA, and among subjects with different CA clinical features.

    • Sean P. Polster
    • , Anukriti Sharma
    • , Ceylan Tanes
    • , Alan T. Tang
    • , Patricia Mericko
    • , Ying Cao
    • , Julián Carrión-Penagos
    • , Romuald Girard
    • , Janne Koskimäki
    • , Dongdong Zhang
    • , Agnieszka Stadnik
    • , Sharbel G. Romanos
    • , Seán B. Lyne
    • , Robert Shenkar
    • , Kimberly Yan
    • , Cornelia Lee
    • , Amy Akers
    • , Leslie Morrison
    • , Myranda Robinson
    • , Atif Zafar
    • , Kyle Bittinger
    • , Helen Kim
    • , Jack A. Gilbert
    • , Mark L. Kahn
    • , Le Shen
    •  & Issam A. Awad
  • Article
    | Open Access

    Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.

    • Nicola Whiffin
    • , Konrad J. Karczewski
    • , Xiaolei Zhang
    • , Sonia Chothani
    • , Miriam J. Smith
    • , D. Gareth Evans
    • , Angharad M. Roberts
    • , Nicholas M. Quaife
    • , Sebastian Schafer
    • , Owen Rackham
    • , Jessica Alföldi
    • , Anne H. O’Donnell-Luria
    • , Laurent C. Francioli
    • , Irina M. Armean
    • , Eric Banks
    • , Louis Bergelson
    • , Kristian Cibulskis
    • , Ryan L. Collins
    • , Kristen M. Connolly
    • , Miguel Covarrubias
    • , Beryl Cummings
    • , Mark J. Daly
    • , Stacey Donnelly
    • , Yossi Farjoun
    • , Steven Ferriera
    • , Stacey Gabriel
    • , Laura D. Gauthier
    • , Jeff Gentry
    • , Namrata Gupta
    • , Thibault Jeandet
    • , Diane Kaplan
    • , Kristen M. Laricchia
    • , Christopher Llanwarne
    • , Eric V. Minikel
    • , Ruchi Munshi
    • , Benjamin M. Neale
    • , Sam Novod
    • , Nikelle Petrillo
    • , Timothy Poterba
    • , David Roazen
    • , Valentin Ruano-Rubio
    • , Andrea Saltzman
    • , Kaitlin E. Samocha
    • , Molly Schleicher
    • , Cotton Seed
    • , Matthew Solomonson
    • , Jose Soto
    • , Grace Tiao
    • , Kathleen Tibbetts
    • , Charlotte Tolonen
    • , Christopher Vittal
    • , Gordon Wade
    • , Arcturus Wang
    • , Qingbo Wang
    • , Nicholas A. Watts
    • , Ben Weisburd
    • , Carlos A. Aguilar Salinas
    • , Tariq Ahmad
    • , Christine M. Albert
    • , Diego Ardissino
    • , Gil Atzmon
    • , John Barnard
    • , Laurent Beaugerie
    • , Emelia J. Benjamin
    • , Michael Boehnke
    • , Lori L. Bonnycastle
    • , Erwin P. Bottinger
    • , Donald W. Bowden
    • , Matthew J. Bown
    • , John C. Chambers
    • , Juliana C. Chan
    • , Daniel Chasman
    • , Judy Cho
    • , Mina K. Chung
    • , Bruce Cohen
    • , Adolfo Correa
    • , Dana Dabelea
    • , Mark J. Daly
    • , Dawood Darbar
    • , Ravindranath Duggirala
    • , Josée Dupuis
    • , Patrick T. Ellinor
    • , Roberto Elosua
    • , Jeanette Erdmann
    • , Tõnu Esko
    • , Martti Färkkilä
    • , Jose Florez
    • , Andre Franke
    • , Gad Getz
    • , Benjamin Glaser
    • , Stephen J. Glatt
    • , David Goldstein
    • , Clicerio Gonzalez
    • , Leif Groop
    • , Christopher Haiman
    • , Craig Hanis
    • , Matthew Harms
    • , Mikko Hiltunen
    • , Matti M. Holi
    • , Christina M. Hultman
    • , Mikko Kallela
    • , Jaakko Kaprio
    • , Sekar Kathiresan
    • , Bong-Jo Kim
    • , Young Jin Kim
    • , George Kirov
    • , Jaspal Kooner
    • , Seppo Koskinen
    • , Harlan M. Krumholz
    • , Subra Kugathasan
    • , Soo Heon Kwak
    • , Markku Laakso
    • , Terho Lehtimäki
    • , Ruth J. F. Loos
    • , Steven A. Lubitz
    • , Ronald C. W. Ma
    • , Jaume Marrugat
    • , Kari M. Mattila
    • , Steven McCarroll
    • , Mark I. McCarthy
    • , Dermot McGovern
    • , Ruth McPherson
    • , James B. Meigs
    • , Olle Melander
    • , Andres Metspalu
    • , Benjamin M. Neale
    • , Peter M. Nilsson
    • , Michael C. O’Donovan
    • , Dost Ongur
    • , Lorena Orozco
    • , Michael J. Owen
    • , Colin N. A. Palmer
    • , Aarno Palotie
    • , Kyong Soo Park
    • , Carlos Pato
    • , Ann E. Pulver
    • , Nazneen Rahman
    • , Anne M. Remes
    • , John D. Rioux
    • , Samuli Ripatti
    • , Dan M. Roden
    • , Danish Saleheen
    • , Veikko Salomaa
    • , Nilesh J. Samani
    • , Jeremiah Scharf
    • , Heribert Schunkert
    • , Moore B. Shoemaker
    • , Pamela Sklar
    • , Hilkka Soininen
    • , Harry Sokol
    • , Tim Spector
    • , Patrick F. Sullivan
    • , Jaana Suvisaari
    • , E. Shyong Tai
    • , Yik Ying Teo
    • , Tuomi Tiinamaija
    • , Ming Tsuang
    • , Dan Turner
    • , Teresa Tusie-Luna
    • , Erkki Vartiainen
    • , Hugh Watkins
    • , Rinse K. Weersma
    • , Maija Wessman
    • , James G. Wilson
    • , Ramnik J. Xavier
    • , Stuart A. Cook
    • , Paul J. R. Barton
    • , Daniel G. MacArthur
    •  & James S. Ware
  • Review Article
    | Open Access

    Between 2014 and 2023, 100,000 UK Biobank participants are undergoing brain, heart and abdominal MRI, as well as DXA and carotid ultrasound scans. In this review, authors provide a detailed overview of the rationale for the collection of these imaging data, the procedures of data collection and management, and the future directions of the UK biobank imaging enhancement.

    • Thomas J. Littlejohns
    • , Jo Holliday
    • , Lorna M. Gibson
    • , Steve Garratt
    • , Niels Oesingmann
    • , Fidel Alfaro-Almagro
    • , Jimmy D. Bell
    • , Chris Boultwood
    • , Rory Collins
    • , Megan C. Conroy
    • , Nicola Crabtree
    • , Nicola Doherty
    • , Alejandro F. Frangi
    • , Nicholas C. Harvey
    • , Paul Leeson
    • , Karla L. Miller
    • , Stefan Neubauer
    • , Steffen E. Petersen
    • , Jonathan Sellors
    • , Simon Sheard
    • , Stephen M. Smith
    • , Cathie L. M. Sudlow
    • , Paul M. Matthews
    •  & Naomi E. Allen
  • Article
    | Open Access

    Ultrasensitive methods for detection of biomarkers for infectious disease are needed for diagnosing, monitoring and targeting treatment. Here the authors develop a digital assay for inflammatory markers, bacterial DNA and antibotic-resistance genes and apply it to characterise asthma patients and predict mortality from septic shock.

    • M. Fatih Abasıyanık
    • , Krysta Wolfe
    • , Hoang Van Phan
    • , Jing Lin
    • , Bharathi Laxman
    • , Steven R. White
    • , Philip A. Verhoef
    • , Gökhan M. Mutlu
    • , Bhakti Patel
    •  & Savaş Tay
  • 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

    Poly-functional helper T cells can have a stronger effect than mono-functional T cells, but whether the response is qualitatively different is not clear. Here the authors show that a population of IL-17+IL-22+, but not single IL-22+, CD4+ T cells are induced by TGF-β, enriched in patients with colorectal cancer (CRC) and drive CRC progression in mice.

    • Laura Garcia Perez
    • , Jan Kempski
    • , Heather M. McGee
    • , Penelope Pelzcar
    • , Theodora Agalioti
    • , Anastasios Giannou
    • , Leonie Konczalla
    • , Leonie Brockmann
    • , Ramez Wahib
    • , Hao Xu
    • , Maria Carolina Amezcua Vesely
    • , Shiwa Soukou
    • , Babett Steglich
    • , Tanja Bedke
    • , Carolin Manthey
    • , Oliver Seiz
    • , Björn-Philipp Diercks
    • , Stylianos Gnafakis
    • , Andreas H. Guse
    • , Daniel Perez
    • , Jakob R. Izbicki
    • , Nicola Gagliani
    • , Richard A. Flavell
    •  & Samuel Huber
  • Article
    | Open Access

    Many germline variants are found in the BRCA2 gene, some of which pre-dispose women to breast and ovarian cancer. Here, the authors develop a method to determine the functional significance of BRCA2 variants and show that it is comparable to the IARC system of classifying variants.

    • Masachika Ikegami
    • , Shinji Kohsaka
    • , Toshihide Ueno
    • , Yukihide Momozawa
    • , Satoshi Inoue
    • , Kenji Tamura
    • , Akihiko Shimomura
    • , Noriko Hosoya
    • , Hiroshi Kobayashi
    • , Sakae Tanaka
    •  & Hiroyuki Mano
  • 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

    How cardiomyocytes mature and what regulates this is unclear. Here, the authors use single-cell analysis to examine how the population of murine cardiac fibroblasts changes during development and affects maturation of cardiomyocytes.

    • Yin Wang
    • , Fang Yao
    • , Lipeng Wang
    • , Zheng Li
    • , Zongna Ren
    • , Dandan Li
    • , Mingzhi Zhang
    • , Leng Han
    • , Shi-qiang Wang
    • , Bingying Zhou
    •  & Li Wang
  • Article
    | Open Access

    The cytokine IFNα is expressed in the islets of individuals with type 1 diabetes and contributes to local inflammation and destruction of beta cells. Here, the authors provide a global multiomics view of IFNα-induced changes in human beta cells at the level of chromatin, mRNA and protein expression.

    • Maikel L. Colli
    • , Mireia Ramos-Rodríguez
    • , Ernesto S. Nakayasu
    • , Maria I. Alvelos
    • , Miguel Lopes
    • , Jessica L. E. Hill
    • , Jean-Valery Turatsinze
    • , Alexandra Coomans de Brachène
    • , Mark A. Russell
    • , Helena Raurell-Vila
    • , Angela Castela
    • , Jonàs Juan-Mateu
    • , Bobbie-Jo M. Webb-Robertson
    • , Lars Krogvold
    • , Knut Dahl-Jorgensen
    • , Lorella Marselli
    • , Piero Marchetti
    • , Sarah J. Richardson
    • , Noel G. Morgan
    • , Thomas O. Metz
    • , Lorenzo Pasquali
    •  & Décio L. Eizirik
  • 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

    Dysregulation of N6-Methyladenosine (m6A) is associated with cancer progression. Here, authors show that m6A methylation of pyruvate dehydrogenase kinase 4 (PDK4) positively regulates its mRNA stability and translation, and consequently affects glycolysis in cancer cells

    • Zihan Li
    • , Yanxi Peng
    • , Jiexin Li
    • , Zhuojia Chen
    • , Feng Chen
    • , Jian Tu
    • , Shuibin Lin
    •  & Hongsheng Wang
  • 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

    Disease stress-induced cardiac hypertrophy is a major mechanism of pathological cardiac remodeling. Here, the authors unveil a previously unrecognized role of a FoxO1–Dio2 signaling axis in maladaptive, afterload-induced cardiac hypertrophy and intracellular thyroid hormone homeostasis.

    • Anwarul Ferdous
    • , Zhao V. Wang
    • , Yuxuan Luo
    • , Dan L. Li
    • , Xiang Luo
    • , Gabriele G. Schiattarella
    • , Francisco Altamirano
    • , Herman I. May
    • , Pavan K. Battiprolu
    • , Annie Nguyen
    • , Beverly A. Rothermel
    • , Sergio Lavandero
    • , Thomas G. Gillette
    •  & Joseph A. Hill
  • 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

    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

    Electronic Health Records (EHR) are subject to noise, biases and missing data. Here, the authors present MixEHR, a multi-view Bayesian framework related to collaborative filtering and latent topic models for EHR data integration and modeling.

    • Yue Li
    • , Pratheeksha Nair
    • , Xing Han Lu
    • , Zhi Wen
    • , Yuening Wang
    • , Amir Ardalan Kalantari Dehaghi
    • , Yan Miao
    • , Weiqi Liu
    • , Tamas Ordog
    • , Joanna M. Biernacka
    • , Euijung Ryu
    • , Janet E. Olson
    • , Mark A. Frye
    • , Aihua Liu
    • , Liming Guo
    • , Ariane Marelli
    • , Yuri Ahuja
    • , Jose Davila-Velderrain
    •  & Manolis Kellis
  • Article
    | Open Access

    On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

    • Ioanna Ntalla
    • , Lu-Chen Weng
    • , James H. Cartwright
    • , Amelia Weber Hall
    • , Gardar Sveinbjornsson
    • , Nathan R. Tucker
    • , Seung Hoan Choi
    • , Mark D. Chaffin
    • , Carolina Roselli
    • , Michael R. Barnes
    • , Borbala Mifsud
    • , Helen R. Warren
    • , Caroline Hayward
    • , Jonathan Marten
    • , James J. Cranley
    • , Maria Pina Concas
    • , Paolo Gasparini
    • , Thibaud Boutin
    • , Ivana Kolcic
    • , Ozren Polasek
    • , Igor Rudan
    • , Nathalia M. Araujo
    • , Maria Fernanda Lima-Costa
    • , Antonio Luiz P. Ribeiro
    • , Renan P. Souza
    • , Eduardo Tarazona-Santos
    • , Vilmantas Giedraitis
    • , Erik Ingelsson
    • , Anubha Mahajan
    • , Andrew P. Morris
    • , Fabiola Del Greco M
    • , Luisa Foco
    • , Martin Gögele
    • , Andrew A. Hicks
    • , James P. Cook
    • , Lars Lind
    • , Cecilia M. Lindgren
    • , Johan Sundström
    • , Christopher P. Nelson
    • , Muhammad B. Riaz
    • , Nilesh J. Samani
    • , Gianfranco Sinagra
    • , Sheila Ulivi
    • , Mika Kähönen
    • , Pashupati P. Mishra
    • , Nina Mononen
    • , Kjell Nikus
    • , Mark J. Caulfield
    • , Anna Dominiczak
    • , Sandosh Padmanabhan
    • , May E. Montasser
    • , Jeff R. O’Connell
    • , Kathleen Ryan
    • , Alan R. Shuldiner
    • , Stefanie Aeschbacher
    • , David Conen
    • , Lorenz Risch
    • , Sébastien Thériault
    • , Nina Hutri-Kähönen
    • , Terho Lehtimäki
    • , Leo-Pekka Lyytikäinen
    • , Olli T. Raitakari
    • , Catriona L. K. Barnes
    • , Harry Campbell
    • , Peter K. Joshi
    • , James F. Wilson
    • , Aaron Isaacs
    • , Jan A. Kors
    • , Cornelia M. van Duijn
    • , Paul L. Huang
    • , Vilmundur Gudnason
    • , Tamara B. Harris
    • , Lenore J. Launer
    • , Albert V. Smith
    • , Erwin P. Bottinger
    • , Ruth J. F. Loos
    • , Girish N. Nadkarni
    • , Michael H. Preuss
    • , Adolfo Correa
    • , Hao Mei
    • , James Wilson
    • , Thomas Meitinger
    • , Martina Müller-Nurasyid
    • , Annette Peters
    • , Melanie Waldenberger
    • , Massimo Mangino
    • , Timothy D. Spector
    • , Michiel Rienstra
    • , Yordi J. van de Vegte
    • , Pim van der Harst
    • , Niek Verweij
    • , Stefan Kääb
    • , Katharina Schramm
    • , Moritz F. Sinner
    • , Konstantin Strauch
    • , Michael J. Cutler
    • , Diane Fatkin
    • , Barry London
    • , Morten Olesen
    • , Dan M. Roden
    • , M. Benjamin Shoemaker
    • , J. Gustav Smith
    • , Mary L. Biggs
    • , Joshua C. Bis
    • , Jennifer A. Brody
    • , Bruce M. Psaty
    • , Kenneth Rice
    • , Nona Sotoodehnia
    • , Alessandro De Grandi
    • , Christian Fuchsberger
    • , Cristian Pattaro
    • , Peter P. Pramstaller
    • , Ian Ford
    • , J. Wouter Jukema
    • , Peter W. Macfarlane
    • , Stella Trompet
    • , Marcus Dörr
    • , Stephan B. Felix
    • , Uwe Völker
    • , Stefan Weiss
    • , Aki S. Havulinna
    • , Antti Jula
    • , Katri Sääksjärvi
    • , Veikko Salomaa
    • , Xiuqing Guo
    • , Susan R. Heckbert
    • , Henry J. Lin
    • , Jerome I. Rotter
    • , Kent D. Taylor
    • , Jie Yao
    • , Renée de Mutsert
    • , Arie C. Maan
    • , Dennis O. Mook-Kanamori
    • , Raymond Noordam
    • , Francesco Cucca
    • , Jun Ding
    • , Edward G. Lakatta
    • , Yong Qian
    • , Kirill V. Tarasov
    • , Daniel Levy
    • , Honghuang Lin
    • , Christopher H. Newton-Cheh
    • , Kathryn L. Lunetta
    • , Alison D. Murray
    • , David J. Porteous
    • , Blair H. Smith
    • , Bruno H. Stricker
    • , André Uitterlinden
    • , Marten E. van den Berg
    • , Jeffrey Haessler
    • , Rebecca D. Jackson
    • , Charles Kooperberg
    • , Ulrike Peters
    • , Alexander P. Reiner
    • , Eric A. Whitsel
    • , Alvaro Alonso
    • , Dan E. Arking
    • , Eric Boerwinkle
    • , Georg B. Ehret
    • , Elsayed Z. Soliman
    • , Christy L. Avery
    • , Stephanie M. Gogarten
    • , Kathleen F. Kerr
    • , Cathy C. Laurie
    • , Amanda A. Seyerle
    • , Adrienne Stilp
    • , Solmaz Assa
    • , M. Abdullah Said
    • , M. Yldau van der Ende
    • , Pier D. Lambiase
    • , Michele Orini
    • , Julia Ramirez
    • , Stefan Van Duijvenboden
    • , David O. Arnar
    • , Daniel F. Gudbjartsson
    • , Hilma Holm
    • , Patrick Sulem
    • , Gudmar Thorleifsson
    • , Rosa B. Thorolfsdottir
    • , Unnur Thorsteinsdottir
    • , Emelia J. Benjamin
    • , Andrew Tinker
    • , Kari Stefansson
    • , Patrick T. Ellinor
    • , Yalda Jamshidi
    • , Steven A. Lubitz
    •  & Patricia B. Munroe
  • 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