Medical research

  • 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

    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

    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

    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

    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

    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

    Impact of pneumococcal conjugate vaccines (PCV) in controlling carriage needs to be evaluated to inform vaccine policy. Here, Swarthout et al. show in a prospective rolling cross-sectional study in Malawi a high residual prevalence of vaccine-serotype S. pneumoniae 7 years after PCV introduction.

    • Todd D. Swarthout
    • , Claudio Fronterre
    • , José Lourenço
    • , Uri Obolski
    • , Andrea Gori
    • , Naor Bar-Zeev
    • , Dean Everett
    • , Arox W. Kamng’ona
    • , Thandie S. Mwalukomo
    • , Andrew A. Mataya
    • , Charles Mwansambo
    • , Marjory Banda
    • , Sunetra Gupta
    • , Peter Diggle
    • , Neil French
    •  & Robert S. Heyderman
  • Article
    | Open Access

    Mutations in PTEN have been associated with various human disease, including autism spectrum disorder (ASD) and cancer. Here, the authors assess the function of 106 PTEN variants in yeast, invertebrate models and cell culture and report that PTEN variants generally decrease protein stability.

    • Kathryn L. Post
    • , Manuel Belmadani
    • , Payel Ganguly
    • , Fabian Meili
    • , Riki Dingwall
    • , Troy A. McDiarmid
    • , Warren M. Meyers
    • , Caitlin Herrington
    • , Barry P. Young
    • , Daniel B. Callaghan
    • , Sanja Rogic
    • , Matthew Edwards
    • , Ana Niciforovic
    • , Alessandro Cau
    • , Catharine H. Rankin
    • , Timothy P. O’Connor
    • , Shernaz X. Bamji
    • , Christopher J. R. Loewen
    • , Douglas W. Allan
    • , Paul Pavlidis
    •  & Kurt Haas
  • Article
    | Open Access

    Multidrug resistance of the opportunistic pathogen Stenotrophomonas maltophilia is an increasing problem. Here, analyzing strains from 22 countries, the authors show that the S. maltophilia complex is divided into 23 monophyletic lineages and find evidence for intra-hospital transmission.

    • Matthias I. Gröschel
    • , Conor J. Meehan
    • , Ivan Barilar
    • , Margo Diricks
    • , Aitor Gonzaga
    • , Matthias Steglich
    • , Oscar Conchillo-Solé
    • , Isabell-Christin Scherer
    • , Uwe Mamat
    • , Christian F. Luz
    • , Katrien De Bruyne
    • , Christian Utpatel
    • , Daniel Yero
    • , Isidre Gibert
    • , Xavier Daura
    • , Stefanie Kampmeier
    • , Nurdyana Abdul Rahman
    • , Michael Kresken
    • , Tjip S. van der Werf
    • , Ifey Alio
    • , Wolfgang R. Streit
    • , Kai Zhou
    • , Thomas Schwartz
    • , John W. A. Rossen
    • , Maha R. Farhat
    • , Ulrich E. Schaible
    • , Ulrich Nübel
    • , Jan Rupp
    • , Joerg Steinmann
    • , Stefan Niemann
    •  & Thomas A. Kohl
  • Article
    | Open Access

    Epidemiological studies have shown an association between sedentary behaviours and cardiovascular disease risk. Here, van de Vegte et al. perform GWAS for self-reported sedentary behaviours (TV watching, computer use, driving) and Mendelian randomization analyses to explore potential causal relationships with coronary artery disease.

    • Yordi J. van de Vegte
    • , M. Abdullah Said
    • , Michiel Rienstra
    • , Pim van der Harst
    •  & Niek Verweij
  • Article
    | Open Access

    Currently a cell-resolution map of the human cornea can only be obtained in the clinic with a confocal microscope in contact with the eye. Here the authors develop a full-field/spectral-domain OCT microscope (FF/SD OCT) to enable cell-level detail of the entire ocular surface, as well as blood flow and tear dynamics.

    • Viacheslav Mazlin
    • , Peng Xiao
    • , Jules Scholler
    • , Kristina Irsch
    • , Kate Grieve
    • , Mathias Fink
    •  & A. Claude Boccara
  • Article
    | Open Access

    Sex differences in the immune response to vaccines and infections have been well described in children and adults. Here the authors describe, in a cohort of 177 HIV-infected infants, innate immune sex differences in fetal life that increase female susceptibility to intrauterine HIV infection and increase the chances of subsequent HIV remission in infected males.

    • Emily Adland
    • , Jane Millar
    • , Nomonde Bengu
    • , Maximilian Muenchhoff
    • , Rowena Fillis
    • , Kenneth Sprenger
    • , Vuyokasi Ntlantsana
    • , Julia Roider
    • , Vinicius Vieira
    • , Katya Govender
    • , John Adamson
    • , Nelisiwe Nxele
    • , Christina Ochsenbauer
    • , John Kappes
    • , Luisa Mori
    • , Jeroen van Lobenstein
    • , Yeney Graza
    • , Kogielambal Chinniah
    • , Constant Kapongo
    • , Roopesh Bhoola
    • , Malini Krishna
    • , Philippa C. Matthews
    • , Ruth Penya Poderos
    • , Marta Colomer Lluch
    • , Maria C. Puertas
    • , Julia G. Prado
    • , Neil McKerrow
    • , Moherndran Archary
    • , Thumbi Ndung’u
    • , Andreas Groll
    • , Pieter Jooste
    • , Javier Martinez-Picado
    • , Marcus Altfeld
    •  & Philip Goulder
  • Article
    | Open Access

    Non-human primate models are important for the development of high quality vision restoration therapies for blindness. Here, the authors demonstrate restoration of light responses in foveal retinal ganglion cells of the living macaque following optogenetic gene therapy.

    • Juliette E. McGregor
    • , Tyler Godat
    • , Kamal R. Dhakal
    • , Keith Parkins
    • , Jennifer M. Strazzeri
    • , Brittany A. Bateman
    • , William S. Fischer
    • , David R. Williams
    •  & William H. Merigan
  • Article
    | Open Access

    Around half of the heritability underpinning familial high-grade serous ovarian carcinoma remains unidentified. Here, the authors show that extremely rare protein encoding loss-of-function variants, with a high degree of genetic heterogeneity, may account for some of this missing heritability.

    • Deepak N. Subramanian
    • , Magnus Zethoven
    • , Simone McInerny
    • , James A. Morgan
    • , Simone M. Rowley
    • , Jue Er Amanda Lee
    • , Na Li
    • , Kylie L. Gorringe
    • , Paul A. James
    •  & Ian G. Campbell
  • Article
    | Open Access

    Whilst pigmentation has been used to identify retinal pigment epithelial (RPE) cells, surface markers for these cells remain unclear. Here, the authors define surface markers for the RPE including CD140b, which help produce hPSC-derived RPE cells at a large scale following a robust, direct and scalable monolayer differentiation protocol.

    • Alvaro Plaza Reyes
    • , Sandra Petrus-Reurer
    • , Sara Padrell Sánchez
    • , Pankaj Kumar
    • , Iyadh Douagi
    • , Hammurabi Bartuma
    • , Monica Aronsson
    • , Sofie Westman
    • , Emma Lardner
    • , Helder André
    • , Anna Falk
    • , Emeline F. Nandrot
    • , Anders Kvanta
    •  & Fredrik Lanner
  • Article
    | Open Access

    Incidence of food allergy in westernized populations is associated with low abundance of Prevotella. Here, the authors analyse the microbiome of a mother-infant prebirth cohort and find that maternal carriage, but not infant carriage, of P. copri during pregnancy predicts the absence of food allergy in the offspring.

    • Peter J. Vuillermin
    • , Martin O’Hely
    • , Fiona Collier
    • , Katrina J. Allen
    • , Mimi L. K. Tang
    • , Leonard C. Harrison
    • , John B. Carlin
    • , Richard Saffery
    • , Sarath Ranganathan
    • , Peter D. Sly
    • , Lawrence Gray
    • , John Molloy
    • , Angela Pezic
    • , Michael Conlon
    • , David Topping
    • , Karen Nelson
    • , Charles R. Mackay
    • , Laurence Macia
    • , Jennifer Koplin
    • , Samantha L. Dawson
    • , Margarita Moreno-Betancur
    • , Anne-Louise Ponsonby
    • , Sanjay Vashee
    • , Manolito Torralba
    • , Andres Gomez
    • , Terrence Dwyer
    • , David Burgner
    • , Michael Forrester
    • , Christos Symeonides
    •  & Esther Bandala Sanchez
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis is associated with increased abundance of Staphylococcus and Streptococcus in the lungs. Here, the authors identify a Staphylococcus nepalensis-derived peptide, named corisin, to induce apoptosis of lung epithelial cells and exacerbation of pulmonary fibrosis in mice.

    • Corina N. D’Alessandro-Gabazza
    • , Tetsu Kobayashi
    • , Taro Yasuma
    • , Masaaki Toda
    • , Heejin Kim
    • , Hajime Fujimoto
    • , Osamu Hataji
    • , Atsuro Takeshita
    • , Kota Nishihama
    • , Tomohito Okano
    • , Yuko Okano
    • , Yoichi Nishii
    • , Atsushi Tomaru
    • , Kentaro Fujiwara
    • , Valeria Fridman D’Alessandro
    • , Ahmed M. Abdel-Hamid
    • , Yudong Ren
    • , Gabriel V. Pereira
    • , Christy L. Wright
    • , Alvaro Hernandez
    • , Christopher J. Fields
    • , Peter M. Yau
    • , Shujie Wang
    • , Akira Mizoguchi
    • , Masayuki Fukumura
    • , Junpei Ohtsuka
    • , Tetsuya Nosaka
    • , Kensuke Kataoka
    • , Yasuhiro Kondoh
    • , Jing Wu
    • , Hirokazu Kawagishi
    • , Yutaka Yano
    • , Roderick I. Mackie
    • , Isaac Cann
    •  & Esteban C. Gabazza
  • Article
    | Open Access

    Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.

    • Ben Hollis
    • , Felix R. Day
    • , Alexander S. Busch
    • , Deborah J. Thompson
    • , Ana Luiza G. Soares
    • , Paul R. H. J. Timmers
    • , Alex Kwong
    • , Doug F. Easton
    • , Peter K. Joshi
    • , Nicholas J. Timpson
    • , Rosalind A. Eeles
    • , Brian E. Henderson
    • , Christopher A. Haiman
    • , Zsofia Kote-Jarai
    • , Fredrick R. Schumacher
    • , Ali Amin Al Olama
    • , Sara Benlloch
    • , Kenneth Muir
    • , Sonja I. Berndt
    • , David V. Conti
    • , Fredrik Wiklund
    • , Stephen Chanock
    • , Susan Gapstur
    • , Victoria L. Stevens
    • , Catherine M. Tangen
    • , Jyotsna Batra
    • , Judith Clements
    • , Wayne Tilley
    • , Gail P. Risbridger
    • , Judith Clements
    • , Lisa Horvath
    • , Renea Taylor
    • , Vanessa Hayes
    • , Lisa Butler
    • , Trina Yeadon
    • , Allison Eckert
    • , Pamela Saunders
    • , Anne-Maree Haynes
    • , Melissa Papargiris
    • , Srilakshmi Srinivasan
    • , Mary-Anne Kedda
    • , Leire Moya
    • , Jyotsna Batra
    • , Henrik Gronberg
    • , Nora Pashayan
    • , Johanna Schleutker
    • , Demetrius Albanes
    • , Alicja Wolk
    • , Catharine West
    • , Lorelei Mucci
    • , Géraldine Cancel-Tassin
    • , Stella Koutros
    • , Karina Dalsgaard Sorensen
    • , Eli Marie Grindedal
    • , David E. Neal
    • , Freddie C. Hamdy
    • , Jenny L. Donovan
    • , Ruth C. Travis
    • , Robert J. Hamilton
    • , Sue Ann Ingles
    • , Barry S. Rosenstein
    • , Yong-Jie Lu
    • , Graham G. Giles
    • , Adam S. Kibel
    • , Ana Vega
    • , Manolis Kogevinas
    • , Kathryn L. Penney
    • , Jong Y. Park
    • , Janet L. Stanford
    • , Cezary Cybulski
    • , Børge G. Nordestgaard
    • , Hermann Brenner
    • , Christiane Maier
    • , Jeri Kim
    • , Esther M. John
    • , Manuel R. Teixeira
    • , Susan L. Neuhausen
    • , Kim De Ruyck
    • , Azad Razack
    • , Lisa F. Newcomb
    • , Davor Lessel
    • , Radka Kaneva
    • , Nawaid Usmani
    • , Frank Claessens
    • , Paul A. Townsend
    • , Manuela Gago-Dominguez
    • , Monique J. Roobol
    • , Florence Menegaux
    • , Kay-Tee Khaw
    • , Lisa Cannon-Albright
    • , Hardev Pandha
    • , Stephen N. Thibodeau
    • , Michelle Agee
    • , Babak Alipanahi
    • , Adam Auton
    • , Robert K. Bell
    • , Katarzyna Bryc
    • , Sarah L. Elson
    • , Pierre Fontanillas
    • , Nicholas A. Furlotte
    • , David A. Hinds
    • , Karen E. Huber
    • , Aaron Kleinman
    • , Nadia K. Litterman
    • , Matthew H. McIntyre
    • , Joanna L. Mountain
    • , Elizabeth S. Noblin
    • , Carrie A. M. Northover
    • , Steven J. Pitts
    • , J. Fah Sathirapongsasuti
    • , Olga V. Sazonova
    • , Janie F. Shelton
    • , Suyash Shringarpure
    • , Chao Tian
    • , Joyce Y. Tung
    • , Vladimir Vacic
    • , Catherine H. Wilson
    • , Ken K. Ong
    •  & John R. B. Perry
  • Article
    | Open Access

    Inherited alterations of the 8q24 genomic locus are linked to cancer etiology. Here, the authors investigate hereditary prostate cancer to reveal ancestral risk-altering haplotypes, the sentinel genetic variants optimally predicting risk, and causal mutation candidates.

    • William D. Dupont
    • , Joan P. Breyer
    • , W. Dale Plummer
    • , Sam S. Chang
    • , Michael S. Cookson
    • , Joseph A. Smith
    • , Elizabeth Blue
    • , Michael Bamshad
    • , Jessica Chong
    • , Deborah Nickerson
    • , Elizabeth E. Blue
    • , Michael J. Bamshad
    •  & Jeffrey R. Smith
  • Article
    | Open Access

    The serotonin transporter (SERT) terminates serotonin signaling and its activity is modulated by antidepressants. Here authors reveal the mechanistic details underlying the coupling between the two binding sites in SERT and a high-affinity ligand for the allosteric site.

    • Per Plenge
    • , Ara M. Abramyan
    • , Gunnar Sørensen
    • , Arne Mørk
    • , Pia Weikop
    • , Ulrik Gether
    • , Benny Bang-Andersen
    • , Lei Shi
    •  & Claus J. Loland
  • Article
    | Open Access

    A Phase I/II trial previously revealed variable anti-tumor efficacy of the PARP inhibitor niraparib in combination with the PD-1 inhibitor pembrolizumab in platinum-resistant ovarian cancer patients. Here, the authors perform an integrated genomic and immunomics analysis of tumor samples from the same patients and find potential predictive biomarkers of response to such combination therapy.

    • Anniina Färkkilä
    • , Doga C. Gulhan
    • , Julia Casado
    • , Connor A. Jacobson
    • , Huy Nguyen
    • , Bose Kochupurakkal
    • , Zoltan Maliga
    • , Clarence Yapp
    • , Yu-An Chen
    • , Denis Schapiro
    • , Yinghui Zhou
    • , Julie R. Graham
    • , Bruce J. Dezube
    • , Pamela Munster
    • , Sandro Santagata
    • , Elizabeth Garcia
    • , Scott Rodig
    • , Ana Lako
    • , Dipanjan Chowdhury
    • , Geoffrey I. Shapiro
    • , Ursula A. Matulonis
    • , Peter J. Park
    • , Sampsa Hautaniemi
    • , Peter K. Sorger
    • , Elizabeth M. Swisher
    • , Alan D. D’Andrea
    •  & Panagiotis A. Konstantinopoulos
  • Article
    | Open Access

    Mechanisms regulating the formation of pre-metastatic niches remain poorly understood. Here, the authors show that ITGBL1-containing extracellular vesicles derived from primary colorectal cancer cells activate the production of inflammatory cytokines by resident fibroblasts in distant organs, promoting metastatic cancer growth.

    • Qing Ji
    • , Lihong Zhou
    • , Hua Sui
    • , Liu Yang
    • , Xinnan Wu
    • , Qing Song
    • , Ru Jia
    • , Ruixiao Li
    • , Jian Sun
    • , Ziyuan Wang
    • , Ningning Liu
    • , Yuanyuan Feng
    • , Xiaoting Sun
    • , Gang Cai
    • , Yu Feng
    • , Jianfeng Cai
    • , Yihai Cao
    • , Guoxiang Cai
    • , Yan Wang
    •  & Qi Li
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease and adult lung spheroid cells have been shown to promote regeneration in animal models of IPF. Here the authors show that the secretome and exosomes of lung spheroid cells is effective as inhalation treatment in rodent models of lung injury and fibrosis and superior to the counterparts derived from mesenchymal stem cells.

    • Phuong-Uyen C. Dinh
    • , Dipti Paudel
    • , Hayden Brochu
    • , Kristen D. Popowski
    • , M. Cyndell Gracieux
    • , Jhon Cores
    • , Ke Huang
    • , M. Taylor Hensley
    • , Erin Harrell
    • , Adam C. Vandergriff
    • , Arianna K. George
    • , Raina T. Barrio
    • , Shiqi Hu
    • , Tyler A. Allen
    • , Kevin Blackburn
    • , Thomas G. Caranasos
    • , Xinxia Peng
    • , Lauren V. Schnabel
    • , Kenneth B. Adler
    • , Leonard J. Lobo
    • , Michael B. Goshe
    •  & Ke Cheng
  • Article
    | Open Access

    Food allergy is triggered by IgE, but some individuals are not allergic to peanuts despite making peanut-specific IgE, and are considered peanut-tolerant. Here, the authors identify differences in blood immune cell composition of peanut-allergic and tolerant infants using mass cytometry, which may help uncover the mechanism of allergic tolerance.

    • Melanie R. Neeland
    • , Sandra Andorf
    • , Monali Manohar
    • , Diane Dunham
    • , Shu-Chen Lyu
    • , Thanh D. Dang
    • , Rachel L. Peters
    • , Kirsten P. Perrett
    • , Mimi L. K. Tang
    • , Richard Saffery
    • , Jennifer J. Koplin
    •  & Kari C. Nadeau
  • Article
    | Open Access

    Changes in the pulmonary membrane, caused by bacterial infection, form part of the pathology of pneumonia. Here, the authors report on a graphene-based oxygen sensor which is used along with X-ray diffraction and AFM to measure the structural changes and changes in oxygen permeability of pulmonary membranes associated with bacterial pneumonia.

    • Mijung Kim
    • , Marilyn Porras-Gomez
    •  & Cecilia Leal
  • Article
    | Open Access

    In Mendelian randomization (MR) studies, one typically selects SNPs as instrumental variables that do not directly affect the outcome to avoid violation of MR assumptions. Here, Cho et al. present a framework, MR-TRYX, that leverages knowledge of such outliers of horizontal pleiotropy to identify putative causal relationships between exposure and outcome.

    • Yoonsu Cho
    • , Philip C. Haycock
    • , Eleanor Sanderson
    • , Tom R. Gaunt
    • , Jie Zheng
    • , Andrew P. Morris
    • , George Davey Smith
    •  & Gibran Hemani
  • Article
    | Open Access

    HIV prevalence varies throughout Africa, but the contribution of migration remains unclear. Using population-based data from ~22,000 persons, Grabowski et al. show that HIV-positive migrants selectively migrate to high prevalence areas and that out-migrants from these areas geographically disperse.

    • Mary Kate Grabowski
    • , Justin Lessler
    • , Jeremiah Bazaale
    • , Dorean Nabukalu
    • , Justine Nankinga
    • , Betty Nantume
    • , Joseph Ssekasanvu
    • , Steven J. Reynolds
    • , Robert Ssekubugu
    • , Fred Nalugoda
    • , Godfrey Kigozi
    • , Joseph Kagaayi
    • , John S. Santelli
    • , Caitlin Kennedy
    • , Maria J. Wawer
    • , David Serwadda
    • , Larry W. Chang
    •  & Ronald H. Gray
  • Article
    | Open Access

    HIV incidence among sex workers remains high in many settings. Here, the authors utilize individual-level data across ten countries in sub-Saharan Africa and suggest that increasingly punitive and non-protective laws are associated with HIV, and that stigmas and sex work laws may operate jointly in increasing HIV risk.

    • Carrie E. Lyons
    • , Sheree R. Schwartz
    • , Sarah M. Murray
    • , Kate Shannon
    • , Daouda Diouf
    • , Tampose Mothopeng
    • , Seni Kouanda
    • , Anato Simplice
    • , Abo Kouame
    • , Zandile Mnisi
    • , Ubald Tamoufe
    • , Nancy Phaswana-Mafuya
    • , Bai Cham
    • , Fatou M. Drame
    • , Mamadú Aliu Djaló
    •  & Stefan Baral
  • Article
    | Open Access

    Reconstructive microsurgery is limited by the precision that human hands can achieve. Here, the authors demonstrate in a randomized clinical pilot trial the feasibility of robot-assisted supermicrosurgery using a dedicated microsurgical robot for the completion of lymphatico-venous anastomosis in the treatment of breast cancer-related lymphedema

    • Tom J. M. van Mulken
    • , Rutger M. Schols
    • , Andrea M. J. Scharmga
    • , Bjorn Winkens
    • , Raimondo Cau
    • , Ferry B. F. Schoenmakers
    • , Shan S. Qiu
    • , René R. W. J. van der Hulst
    • , Xavier H. A. Keuter
    • , Thomas M. A. S. Lauwers
    • , Andrzej A. Piatkowski
    • , Juliette E. Hommes
    • , Dionne S. Deibel
    • , Jessie E. M. Budo
    • , Jai Scheerhoorn
    •  & Maud E. P. Rijkx
  • Article
    | Open Access

    Neurofilament (NfL) levels in CSF and blood have been established as a biomarker of neuronal damage in neurodegenerative diseases, and there is an age-dependent increase in NfL levels in CSF. Here the authors demonstrate that serum NfL levels increase in healthy aging people and predict and correlate with brain volume loss.

    • Michael Khalil
    • , Lukas Pirpamer
    • , Edith Hofer
    • , Margarete M. Voortman
    • , Christian Barro
    • , David Leppert
    • , Pascal Benkert
    • , Stefan Ropele
    • , Christian Enzinger
    • , Franz Fazekas
    • , Reinhold Schmidt
    •  & Jens Kuhle
  • Article
    | Open Access

    In this longitudinal study, the authors tracked the course of brain development from birth to adolescence (age 13 years) and examined the effects of very preterm birth. Very preterm children showed slower brain growth from age 0 (term equivalent) to age 7.

    • Deanne K. Thompson
    • , Lillian G. Matthews
    • , Bonnie Alexander
    • , Katherine J. Lee
    • , Claire E. Kelly
    • , Chris L. Adamson
    • , Rod W. Hunt
    • , Jeanie L. Y. Cheong
    • , Megan Spencer-Smith
    • , Jeffrey J. Neil
    • , Marc L. Seal
    • , Terrie E. Inder
    • , Lex W. Doyle
    •  & Peter J. Anderson
  • Article
    | Open Access

    APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.

    • Eric M. Reiman
    • , Joseph F. Arboleda-Velasquez
    • , Yakeel T. Quiroz
    • , Matthew J. Huentelman
    • , Thomas G. Beach
    • , Richard J. Caselli
    • , Yinghua Chen
    • , Yi Su
    • , Amanda J. Myers
    • , John Hardy
    • , Jean Paul Vonsattel
    • , Steven G. Younkin
    • , David A. Bennett
    • , Philip L. De Jager
    • , Eric B. Larson
    • , Paul K. Crane
    • , C. Dirk Keene
    • , M. Ilyas Kamboh
    • , Julia K. Kofler
    • , Linda Duque
    • , John R. Gilbert
    • , Harry E. Gwirtsman
    • , Joseph D. Buxbaum
    • , Dennis W. Dickson
    • , Matthew P. Frosch
    • , Bernardino F. Ghetti
    • , Kathryn L. Lunetta
    • , Li-San Wang
    • , Bradley T. Hyman
    • , Walter A. Kukull
    • , Tatiana Foroud
    • , Jonathan L. Haines
    • , Richard P. Mayeux
    • , Margaret A. Pericak-Vance
    • , Julie A. Schneider
    • , John Q. Trojanowski
    • , Lindsay A. Farrer
    • , Gerard D. Schellenberg
    • , Gary W. Beecham
    • , Thomas J. Montine
    • , Gyungah R. Jun
    • , Erin Abner
    • , Perrie M. Adams
    • , Marilyn S. Albert
    • , Roger L. Albin
    • , Liana G. Apostolova
    • , Steven E. Arnold
    • , Sanjay Asthana
    • , Craig S. Atwood
    • , Clinton T. Baldwin
    • , Robert C. Barber
    • , Lisa L. Barnes
    • , Sandra Barral
    • , James T. Becker
    • , Duane Beekly
    • , Eileen H. Bigio
    • , Thomas D. Bird
    • , Deborah Blacker
    • , Bradley F. Boeve
    • , James D. Bowen
    • , Adam Boxer
    • , James R. Burke
    • , Jeffrey M. Burns
    • , Nigel J. Cairns
    • , Laura B. Cantwell
    • , Chuanhai Cao
    • , Chris S. Carlson
    • , Cynthia M. Carlsson
    • , Regina M. Carney
    • , Minerva M. Carrasquillo
    • , Helena C. Chui
    • , David H. Cribbs
    • , Elizabeth A. Crocco
    • , Carlos Cruchaga
    • , Charles DeCarli
    • , Malcolm Dick
    • , Rachelle S. Doody
    • , Ranjan Duara
    • , Nilufer Ertekin-Taner
    • , Denis A. Evans
    • , Kelley M. Faber
    • , Thomas J. Fairchild
    • , Kenneth B. Fallon
    • , David W. Fardo
    • , Martin R. Farlow
    • , Steven Ferris
    • , Douglas R. Galasko
    • , Marla Gearing
    • , Daniel H. Geschwind
    • , Valentina Ghisays
    • , Alison M. Goate
    • , Neill R. Graff-Radford
    • , Robert C. Green
    • , John H. Growdon
    • , Hakon Hakonarson
    • , Ronald L. Hamilton
    • , Kara L. Hamilton-Nelson
    • , Lindy E. Harrell
    • , Lawrence S. Honig
    • , Ryan M. Huebinger
    • , Christine M. Hulette
    • , Gail P. Jarvik
    • , Lee-Way Jin
    • , Anna Karydas
    • , Mindy J. Katz
    • , John S. K. Kauwe
    • , Jeffrey A. Kaye
    • , Ronald Kim
    • , Neil W. Kowall
    • , Joel H. Kramer
    • , Brian W. Kunkle
    • , Amanda P. Kuzma
    • , Frank M. LaFerla
    • , James J. Lah
    • , Yuk Ye Leung
    • , James B. Leverenz
    • , Allan I. Levey
    • , Ge Li
    • , Andrew P. Lieberman
    • , Richard B. Lipton
    • , Oscar L. Lopez
    • , Constantine G. Lyketsos
    • , John Malamon
    • , Daniel C. Marson
    • , Eden R. Martin
    • , Frank Martiniuk
    • , Deborah C. Mash
    • , Eliezer Masliah
    • , Wayne C. McCormick
    • , Susan M. McCurry
    • , Andrew N. McDavid
    • , Stefan McDonough
    • , Ann C. McKee
    • , Marsel Mesulam
    • , Bruce L. Miller
    • , Carol A. Miller
    • , Joshua W. Miller
    • , John C. Morris
    • , Shubhabrata Mukherjee
    • , Adam C. Naj
    • , Sid O’Bryant
    • , John M. Olichney
    • , Joseph E. Parisi
    • , Henry L. Paulson
    • , Elaine Peskind
    • , Ronald C. Petersen
    • , Aimee Pierce
    • , Wayne W. Poon
    • , Huntington Potter
    • , Liming Qu
    • , Joseph F. Quinn
    • , Ashok Raj
    • , Murray Raskind
    • , Barry Reisberg
    • , Joan S. Reisch
    • , Christiane Reitz
    • , John M. Ringman
    • , Erik D. Roberson
    • , Ekaterina Rogaeva
    • , Howard J. Rosen
    • , Roger N. Rosenberg
    • , Donald R. Royall
    • , Mark A. Sager
    • , Mary Sano
    • , Andrew J. Saykin
    • , Lon S. Schneider
    • , William W. Seeley
    • , Amanda G. Smith
    • , Joshua A. Sonnen
    • , Salvatore Spina
    • , Peter St George-Hyslop
    • , Robert A. Stern
    • , Russell H. Swerdlow
    • , Rudolph E. Tanzi
    • , Juan C. Troncoso
    • , Debby W. Tsuang
    • , Otto Valladares
    • , Vivianna M. Van Deerlin
    • , Linda J. Van Eldik
    • , Badri N. Vardarajan
    • , Harry V. Vinters
    • , Sandra Weintraub
    • , Kathleen A. Welsh-Bohmer
    • , Kirk C. Wilhelmsen
    • , Jennifer Williamson
    • , Thomas S. Wingo
    • , Randall L. Woltjer
    • , Clinton B. Wright
    • , Chuang-Kuo Wu
    • , Chang-En Yu
    • , Lei Yu
    •  & Yi Zhao
  • Article
    | Open Access

    Chaperone mediated autophagy (CMA) is selective but its activity in different tissue types has been unclear due to a lack of tools. Here, the authors generate transgenic mice expressing a CMA reporter that provides spatial and temporal in vivo data, uncovering differences in CMA in distinct tissues.

    • S. Dong
    • , C. Aguirre-Hernandez
    • , A. Scrivo
    • , C. Eliscovich
    • , E. Arias
    • , J. J. Bravo-Cordero
    •  & A. M. Cuervo
  • Article
    | Open Access

    Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

    • Pilar Cacheiro
    • , Violeta Muñoz-Fuentes
    • , Stephen A. Murray
    • , Mary E. Dickinson
    • , Maja Bucan
    • , Lauryl M. J. Nutter
    • , Kevin A. Peterson
    • , Hamed Haselimashhadi
    • , Ann M. Flenniken
    • , Hugh Morgan
    • , Henrik Westerberg
    • , Tomasz Konopka
    • , Chih-Wei Hsu
    • , Audrey Christiansen
    • , Denise G. Lanza
    • , Arthur L. Beaudet
    • , Jason D. Heaney
    • , Helmut Fuchs
    • , Valerie Gailus-Durner
    • , Tania Sorg
    • , Jan Prochazka
    • , Vendula Novosadova
    • , Christopher J. Lelliott
    • , Hannah Wardle-Jones
    • , Sara Wells
    • , Lydia Teboul
    • , Heather Cater
    • , Michelle Stewart
    • , Tertius Hough
    • , Wolfgang Wurst
    • , Radislav Sedlacek
    • , David J. Adams
    • , John R. Seavitt
    • , Glauco Tocchini-Valentini
    • , Fabio Mammano
    • , Robert E. Braun
    • , Colin McKerlie
    • , Yann Herault
    • , Martin Hrabě de Angelis
    • , Ann-Marie Mallon
    • , K. C.  Kent Lloyd
    • , Steve D. M. Brown
    • , Helen Parkinson
    • , Terrence F. Meehan
    • , Damian Smedley
    • , J. C. Ambrose
    • , P. Arumugam
    • , E. L. Baple
    • , M. Bleda
    • , F. Boardman-Pretty
    • , J. M. Boissiere
    • , C. R. Boustred
    • , H. Brittain
    • , M. J. Caulfield
    • , G. C. Chan
    • , C. E. H. Craig
    • , L. C. Daugherty
    • , A. de Burca
    • , A. Devereau
    • , G. Elgar
    • , R. E. Foulger
    • , T. Fowler
    • , P. Furió-Tarí
    • , J. M. Hackett
    • , D. Halai
    • , A. Hamblin
    • , S. Henderson
    • , J. E. Holman
    • , T. J. P. Hubbard
    • , K. Ibáñez
    • , R. Jackson
    • , L. J. Jones
    • , D. Kasperaviciute
    • , M. Kayikci
    • , L. Lahnstein
    • , K. Lawson
    • , S. E. A. Leigh
    • , I. U. S. Leong
    • , F. J. Lopez
    • , F. Maleady-Crowe
    • , J. Mason
    • , E. M. McDonagh
    • , L. Moutsianas
    • , M. Mueller
    • , N. Murugaesu
    • , A. C. Need
    • , C. A. Odhams
    • , C. Patch
    • , D. Perez-Gil
    • , D. Polychronopoulos
    • , J. Pullinger
    • , T. Rahim
    • , A. Rendon
    • , P. Riesgo-Ferreiro
    • , T. Rogers
    • , M. Ryten
    • , K. Savage
    • , K. Sawant
    • , R. H. Scott
    • , A. Siddiq
    • , A. Sieghart
    • , K. R. Smith
    • , A. Sosinsky
    • , W. Spooner
    • , H. E. Stevens
    • , A. Stuckey
    • , R. Sultana
    • , E. R. A. Thomas
    • , S. R. Thompson
    • , C. Tregidgo
    • , A. Tucci
    • , E. Walsh
    • , S. A. Watters
    • , M. J. Welland
    • , E. Williams
    • , K. Witkowska
    • , S. M. Wood
    • , M. Zarowiecki
    • , Susan Marschall
    • , Christoph Lengger
    • , Holger Maier
    • , Claudia Seisenberger
    • , Antje Bürger
    • , Ralf Kühn
    • , Joel Schick
    • , Andreas Hörlein
    • , Oskar Oritz
    • , Florian Giesert
    • , Joachim Beig
    • , Janet Kenyon
    • , Gemma Codner
    • , Martin Fray
    • , Sara J. Johnson
    • , James Cleak
    • , Zsombor Szoke-Kovacs
    • , David Lafont
    • , Valerie E. Vancollie
    • , Robbie S. B. McLaren
    • , Lena Hughes-Hallett
    • , Christine Rowley
    • , Emma Sanderson
    • , Antonella Galli
    • , Elizabeth Tuck
    • , Angela Green
    • , Catherine Tudor
    • , Emma Siragher
    • , Monika Dabrowska
    • , Cecilia Icoresi Mazzeo
    • , Mark Griffiths
    • , David Gannon
    • , Brendan Doe
    • , Nicola Cockle
    • , Andrea Kirton
    • , Joanna Bottomley
    • , Catherine Ingle
    • , Edward Ryder
    • , Diane Gleeson
    • , Ramiro Ramirez-Solis
    • , Marie-Christine Birling
    • , Guillaume Pavlovic
    • , Abdel Ayadi
    • , Meziane Hamid
    • , Ghina Bou About
    • , Marie-France Champy
    • , Hugues Jacobs
    • , Olivia Wendling
    • , Sophie Leblanc
    • , Laurent Vasseur
    • , Elissa J. Chesler
    • , Vivek Kumar
    • , Jacqueline K. White
    • , Karen L. Svenson
    • , Jean-Paul Wiegand
    • , Laura L. Anderson
    • , Troy Wilcox
    • , James Clark
    • , Jennifer Ryan
    • , James Denegre
    • , Tim Stearns
    • , Vivek Philip
    • , Catherine Witmeyer
    • , Lindsay Bates
    • , Zachary Seavey
    • , Pamela Stanley
    • , Amelia Willet
    • , Willson Roper
    • , Julie Creed
    • , Michayla Moore
    • , Alex Dorr
    • , Pamelia Fraungruber
    • , Rose Presby
    • , Matthew Mckay
    • , Dong Nguyen-Bresinsky
    • , Leslie Goodwin
    • , Rachel Urban
    •  & Coleen Kane
  • Article
    | Open Access

    Hypoxia in solid tumors is an important factor in radiation therapy resistance, but partial pressures of oxygen in the tissue are heterogenous and difficult to measure. Here the authors develop Cherenkov excited phosphorescence imaging using oxygen probe Oxyphor PtG4 to spatially track oxygen distributions in tumors during fractionated radiotherapy.

    • Xu Cao
    • , Srinivasa Rao Allu
    • , Shudong Jiang
    • , Mengyu Jia
    • , Jason R. Gunn
    • , Cuiping Yao
    • , Ethan P. LaRochelle
    • , Jennifer R. Shell
    • , Petr Bruza
    • , David J. Gladstone
    • , Lesley A. Jarvis
    • , Jie Tian
    • , Sergei A. Vinogradov
    •  & Brian W. Pogue
  • Article
    | Open Access

    Platinum based drugs like cisplatin are common chemotherapy treatments for cancer. Here, the authors report on the in situ formation of platinum nanoparticles in patients and demonstrated how platinum nanoparticles can be synthesized using patients’ blood and provide effective drug delivery and cancer treatments.

    • Xin Zeng
    • , Jie Sun
    • , Suping Li
    • , Jiyun Shi
    • , Han Gao
    • , Wei Sun Leong
    • , Yiqi Wu
    • , Minghui Li
    • , Chengxin Liu
    • , Ping Li
    • , Jing Kong
    • , Yi-Zhou Wu
    • , Guangjun Nie
    • , Yuming Fu
    •  & Gen Zhang
  • Article
    | Open Access

    Population-based association analyses of rare genetic variants with complex traits are limited by the availability of data from sufficiently large cohorts. Here, Cirulli et al. report gene-based collapsing analysis of exomes from 49,960 participants of the UK Biobank and 21,866 participants of the Healthy Nevada Project over a total of 4377 traits.

    • Elizabeth T. Cirulli
    • , Simon White
    • , Robert W. Read
    • , Gai Elhanan
    • , William J. Metcalf
    • , Francisco Tanudjaja
    • , Donna M. Fath
    • , Efren Sandoval
    • , Magnus Isaksson
    • , Karen A. Schlauch
    • , Joseph J. Grzymski
    • , James T. Lu
    •  & Nicole L. Washington
  • Article
    | Open Access

    The pathways that underlie the effects of exercise on metabolism remain incompletely described. Here, the authors perform a meta-analysis of transcriptomic data from 66 published datasets of human skeletal muscle. They identify pathways selectively activated by inactivity, aerobic or resistance exercise, and characterize NR4A3 as one of the genes responsive to inactivity.

    • Nicolas J. Pillon
    • , Brendan M. Gabriel
    • , Lucile Dollet
    • , Jonathon A. B. Smith
    • , Laura Sardón Puig
    • , Javier Botella
    • , David J. Bishop
    • , Anna Krook
    •  & Juleen R. Zierath
  • Article
    | Open Access

    Vascular senescence is closely associated with individual ageing, while its causative role remains unclear. Here Barinda et al. generate endothelial cell-specific progeroind mice, and reveal that endothelial cell senescence directly induces metabolic disorders through senescence-messaging secretomes.

    • Agian Jeffilano Barinda
    • , Koji Ikeda
    • , Dhite Bayu Nugroho
    • , Donytra Arby Wardhana
    • , Naoto Sasaki
    • , Sakiko Honda
    • , Ryota Urata
    • , Satoaki Matoba
    • , Ken-ichi Hirata
    •  & Noriaki Emoto
  • Article
    | Open Access

    Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.

    • Mark Pinese
    • , Paul Lacaze
    • , Emma M. Rath
    • , Andrew Stone
    • , Marie-Jo Brion
    • , Adam Ameur
    • , Sini Nagpal
    • , Clare Puttick
    • , Shane Husson
    • , Dmitry Degrave
    • , Tina Navin Cristina
    • , Vivian F. S. Kahl
    • , Aaron L. Statham
    • , Robyn L. Woods
    • , John J. McNeil
    • , Moeen Riaz
    • , Margo Barr
    • , Mark R. Nelson
    • , Christopher M. Reid
    • , Anne M. Murray
    • , Raj C. Shah
    • , Rory Wolfe
    • , Joshua R. Atkins
    • , Chantel Fitzsimmons
    • , Heath M. Cairns
    • , Melissa J. Green
    • , Vaughan J. Carr
    • , Mark J. Cowley
    • , Hilda A. Pickett
    • , Paul A. James
    • , Joseph E. Powell
    • , Warren Kaplan
    • , Greg Gibson
    • , Ulf Gyllensten
    • , Murray J. Cairns
    • , Martin McNamara
    • , Marcel E. Dinger
    •  & David M. Thomas
  • Article
    | Open Access

    Here, via a metagenomics analysis of population-based and disease cohorts, Vich Vila et al. study the impact of 41 commonly used medications on the taxonomic structures, metabolic potential and resistome of the gut microbiome, underscoring the importance of correcting for multiple drug use in microbiome studies.

    • Arnau Vich Vila
    • , Valerie Collij
    • , Serena Sanna
    • , Trishla Sinha
    • , Floris Imhann
    • , Arno R. Bourgonje
    • , Zlatan Mujagic
    • , Daisy M. A. E. Jonkers
    • , Ad A. M. Masclee
    • , Jingyuan Fu
    • , Alexander Kurilshikov
    • , Cisca Wijmenga
    • , Alexandra Zhernakova
    •  & Rinse K. Weersma
  • Article
    | Open Access

    Mendelian randomization (MR) is a method for inferring causal relationships between risk factors and outcomes via associated genetic variants. Here, Burgess et al. develop the contamination mixture method which yields robust MR results in the presence of invalid instrumental variables and groups variants by their effect estimates.

    • Stephen Burgess
    • , Christopher N Foley
    • , Elias Allara
    • , James R Staley
    •  & Joanna M. M. Howson
  • Article
    | Open Access

    Autophagy declines with age, yet it is unclear if restoration of autophagy extends lifespan. Here, the authors demonstrate in murine models that the inhibition of Atg5 induces ageing phenotypes and reduces lifespan, whilst autophagy restoration partially reverses these phenotypes with accelerated tumorigenesis.

    • Liam D. Cassidy
    • , Andrew R. J. Young
    • , Christopher N. J. Young
    • , Elizabeth J. Soilleux
    • , Edward Fielder
    • , Bettina M. Weigand
    • , Anthony Lagnado
    • , Rebecca Brais
    • , Nicholas T. Ktistakis
    • , Kimberley A. Wiggins
    • , Katerina Pyrillou
    • , Murray C. H. Clarke
    • , Diana Jurk
    • , Joao F. Passos
    •  & Masashi Narita
  • Article
    | Open Access

    Gene expression and how genetic variants can influence gene expression are tissue-specific processes with important implications for phenotypes. Here, Richardson et al. use eQTL data from GTEx and the eQTLGen project in a two-sample SMR + HEIDI framework for causal inference of gene expression associations with complex trait.

    • Tom G. Richardson
    • , Gibran Hemani
    • , Tom R. Gaunt
    • , Caroline L. Relton
    •  & George Davey Smith
  • Article
    | Open Access

    Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.

    • Timothy P. Sheahan
    • , Amy C. Sims
    • , Sarah R. Leist
    • , Alexandra Schäfer
    • , John Won
    • , Ariane J. Brown
    • , Stephanie A. Montgomery
    • , Alison Hogg
    • , Darius Babusis
    • , Michael O. Clarke
    • , Jamie E. Spahn
    • , Laura Bauer
    • , Scott Sellers
    • , Danielle Porter
    • , Joy Y. Feng
    • , Tomas Cihlar
    • , Robert Jordan
    • , Mark R. Denison
    •  & Ralph S. Baric
  • Article
    | Open Access

    An fMRI-based brain signature to predict an individual’s pain sensitivity could be useful clinically. Here the authors identify a network in the resting brain which can be used to predict responses to noxious stimuli in healthy subjects.

    • Tamas Spisak
    • , Balint Kincses
    • , Frederik Schlitt
    • , Matthias Zunhammer
    • , Tobias Schmidt-Wilcke
    • , Zsigmond T. Kincses
    •  & Ulrike Bingel
  • Article
    | Open Access

    mTORC1 is an important regulator of muscle mass. Here, the authors show that the PHD1 controls muscle mass in a hydroxylation-independent manner. PHD1 prevents the degradation of leucine sensor LRS during oxygen and amino acid depletion to ensure effective mTORC1 activation in response to leucine.

    • Gommaar D’Hulst
    • , Inés Soro-Arnaiz
    • , Evi Masschelein
    • , Koen Veys
    • , Gillian Fitzgerald
    • , Benoit Smeuninx
    • , Sunghoon Kim
    • , Louise Deldicque
    • , Bert Blaauw
    • , Peter Carmeliet
    • , Leigh Breen
    • , Peppi Koivunen
    • , Shi-Min Zhao
    •  & Katrien De Bock