Medical research

  • Article
    | Open Access

    Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

    • David Michalovich
    • , Noelia Rodriguez-Perez
    • , Sylwia Smolinska
    • , Michal Pirozynski
    • , David Mayhew
    • , Sorif Uddin
    • , Stephanie Van Horn
    • , Milena Sokolowska
    • , Can Altunbulakli
    • , Andrzej Eljaszewicz
    • , Benoit Pugin
    • , Weronika Barcik
    • , Magdalena Kurnik-Lucka
    • , Ken A. Saunders
    • , Karen D. Simpson
    • , Peter Schmid-Grendelmeier
    • , Ruth Ferstl
    • , Remo Frei
    • , Noriane Sievi
    • , Malcolm Kohler
    • , Pawel Gajdanowicz
    • , Katrine B. Graversen
    • , Katrine Lindholm Bøgh
    • , Marek Jutel
    • , James R. Brown
    • , Cezmi A. Akdis
    • , Edith M. Hessel
    •  & Liam O’Mahony
  • Article
    | Open Access

    Graft versus host disease (GvHD) still hinders allogeneic hematopoietic stem cell transplantation. Here, the authors use metabolomics to analyze two cohorts of paired transplant recipients and donors, identifying significant differences in both host- and microbiota-derived metabolites.

    • David Michonneau
    • , Eleonora Latis
    • , Emmanuel Curis
    • , Laetitia Dubouchet
    • , Sivapriya Ramamoorthy
    • , Brian Ingram
    • , Régis Peffault de Latour
    • , Marie Robin
    • , Flore Sicre de Fontbrune
    • , Sylvie Chevret
    • , Lars Rogge
    •  & Gérard Socié
  • Article
    | Open Access

    Here, Nelson et al. use amplicon next-generation sequencing of two P. falciparum polymorphic gene regions to investigate the genetic similarity of parasite populations across time and space in a pediatric cohort in Kenya. They identify both micro- and macro-scale structuring of malaria parasites in this high-transmission setting, which could inform future intervention strategies.

    • Cody S. Nelson
    • , Kelsey M. Sumner
    • , Elizabeth Freedman
    • , Joseph W. Saelens
    • , Andrew A. Obala
    • , Judith N. Mangeni
    • , Steve M. Taylor
    •  & Wendy P. O’Meara
  • Article
    | Open Access

    Relapse, reinfection and recrudescence can all cause recurrent infection after treatment of Plasmodium vivax malaria in endemic areas, but are difficult to distinguish. Here the authors show that they can be differentiated probabilistically and thereby demonstrate the high efficacy of primaquine treatment in preventing relapse.

    • Aimee R. Taylor
    • , James A. Watson
    • , Cindy S. Chu
    • , Kanokpich Puaprasert
    • , Jureeporn Duanguppama
    • , Nicholas P. J. Day
    • , Francois Nosten
    • , Daniel E. Neafsey
    • , Caroline O. Buckee
    • , Mallika Imwong
    •  & Nicholas J. White
  • Article
    | Open Access

    Siblings of those with autism spectrum disorder (ASD) have increased likelihood of ASD or related subclinical traits. Here, studying 253 ASD families, D’Abate et al. test the predictive value of genomic copy number variation involving ASD-associated loci, with confirmation in a second cohort.

    • L. D’Abate
    • , S. Walker
    • , R. K. C. Yuen
    • , K. Tammimies
    • , J. A. Buchanan
    • , R. W. Davies
    • , B. Thiruvahindrapuram
    • , J. Wei
    • , J. Brian
    • , S. E. Bryson
    • , K. Dobkins
    • , J. Howe
    • , R. Landa
    • , J. Leef
    • , D. Messinger
    • , S. Ozonoff
    • , I. M. Smith
    • , W. L. Stone
    • , Z. E. Warren
    • , G. Young
    • , L. Zwaigenbaum
    •  & S. W. Scherer
  • Article
    | Open Access

    Urinary tract infections (UTIs) are associated with changes in the gut microbiome. Here, the authors evaluate the relationship between the gut microbiome and development of UTI in kidney transplant patients and show that uropathogenic gut abundance might represent a risk factor for development of bacteriuria and UTI.

    • Matthew Magruder
    • , Adam N. Sholi
    • , Catherine Gong
    • , Lisa Zhang
    • , Emmanuel Edusei
    • , Jennifer Huang
    • , Shady Albakry
    • , Michael J. Satlin
    • , Lars F. Westblade
    • , Carl Crawford
    • , Darshana M. Dadhania
    • , Michelle Lubetzky
    • , Ying Taur
    • , Eric Littman
    • , Lilan Ling
    • , Philip Burnham
    • , Iwijn De Vlaminck
    • , Eric Pamer
    • , Manikkam Suthanthiran
    •  & John Richard Lee
  • Article
    | Open Access

    Here, the authors investigate the outcome of prevention services scale-up on HIV incidence in a South African large population-based HIV surveillance cohort with over a decade of follow-up and associate a 43% reduction in incidence to earlier male medical circumcision and increased levels of antiretroviral therapy coverage.

    • Alain Vandormael
    • , Adam Akullian
    • , Mark Siedner
    • , Tulio de Oliveira
    • , Till Bärnighausen
    •  & Frank Tanser
  • Article
    | Open Access

    Higher organisms regulate cellular iron concentrations through Iron Regulatory Proteins (IRPs), which regulate specific messenger RNAs. Here Huynh et al. show that IRP1 requires a Glycogen Branching Enzyme for proper function, and that IRP1 has additional regulatory roles in cell nuclei.

    • Nhan Huynh
    • , Qiuxiang Ou
    • , Pendleton Cox
    • , Roland Lill
    •  & Kirst King-Jones
  • Article
    | Open Access

    Histology data exists for many cancer samples and the ability to automatically image this data may provide prognostic information. Here, the authors generated an algorithm to measure tumour infiltrating lymphocytes in melanoma histology specimens and show that the ratio of these immune cells to tumour cells has prognostic value.

    • Balazs Acs
    • , Fahad Shabbir Ahmed
    • , Swati Gupta
    • , Pok Fai Wong
    • , Robyn D. Gartrell
    • , Jaya Sarin Pradhan
    • , Emanuelle M. Rizk
    • , Bonnie Gould Rothberg
    • , Yvonne M. Saenger
    •  & David L. Rimm
  • Article
    | Open Access

    One measurement of tuberculosis vaccine efficacy in clinical trials is prevention of disease, but different mechanisms can underlie disease prevention. Here, the authors develop a mathematical model that allows to identify mechanisms of action of a vaccine preventing TB disease.

    • Mario Tovar
    • , Sergio Arregui
    • , Dessislava Marinova
    • , Carlos Martín
    • , Joaquín Sanz
    •  & Yamir Moreno
  • Article
    | Open Access

    The efficacy of tumour starvation therapy is limited by lack of persistent tumour suppression, tumour metastasis and recurrence. Here, the authors report biocompatible gold nanorods and thermal-sensitive hydrogel to promote narrowing of blood vessels and show this to reduce tumour growth and metastasis.

    • Kun Zhang
    • , Yan Fang
    • , Yaping He
    • , Haohao Yin
    • , Xin Guan
    • , Yinying Pu
    • , Bangguo Zhou
    • , Wenwen Yue
    • , Weiwei Ren
    • , Dou Du
    • , Hongyan Li
    • , Chang Liu
    • , Liping Sun
    • , Yu Chen
    •  & Huixiong Xu
  • Article
    | Open Access

    Detecting genomic abnormalities in metastatic castration-resistant prostate cancer (mCRPC) may impact clinical treatment. Here, the authors present whole-genome sequencing of metastatic biopsies from 197 mCRPC patients, highlighting the landscape of microsatellite stability, homologous repair deficiency, and other genomic subgroups.

    • Lisanne F. van Dessel
    • , Job van Riet
    • , Minke Smits
    • , Yanyun Zhu
    • , Paul Hamberg
    • , Michiel S. van der Heijden
    • , Andries M. Bergman
    • , Inge M. van Oort
    • , Ronald de Wit
    • , Emile E. Voest
    • , Neeltje Steeghs
    • , Takafumi N. Yamaguchi
    • , Julie Livingstone
    • , Paul C. Boutros
    • , John W. M. Martens
    • , Stefan Sleijfer
    • , Edwin Cuppen
    • , Wilbert Zwart
    • , Harmen J. G. van de Werken
    • , Niven Mehra
    •  & Martijn P. Lolkema
  • Article
    | Open Access

    Whole genome sequencing (WGS) holds promise to solve a subset of Mendelian disease cases for which exome sequencing did not provide a genetic diagnosis. Here, Wells et al. report a supervised machine learning model trained on functional, mutational and structural features for rank-scoring and interpreting variants in non-coding regions from WGS.

    • Alex Wells
    • , David Heckerman
    • , Ali Torkamani
    • , Li Yin
    • , Jonathan Sebat
    • , Bing Ren
    • , Amalio Telenti
    •  & Julia di Iulio
  • Article
    | Open Access

    The ERK signalling pathway is activated in many cancers, however ERK1 and ERK2 are difficult to target pharmacologically. Here, the authors identify a small molecule inhibitor that binds covalently to the D-recruitment site of ERK and induces cell death and reduces tumour growth in mice.

    • Tamer S. Kaoud
    • , William H. Johnson
    • , Nancy D. Ebelt
    • , Andrea Piserchio
    • , Diana Zamora-Olivares
    • , Sabrina X. Van Ravenstein
    • , Jacey R. Pridgen
    • , Ramakrishna Edupuganti
    • , Rachel Sammons
    • , Micael Cano
    • , Mangalika Warthaka
    • , Matthew Harger
    • , Clint D. J. Tavares
    • , Jihyun Park
    • , Mohamed F. Radwan
    • , Pengyu Ren
    • , Eric V. Anslyn
    • , Kenneth Y. Tsai
    • , Ranajeet Ghose
    •  & Kevin N. Dalby
  • Article
    | Open Access

    Cervicovaginal inflammation and human papillomavirus (HPV) are separately associated with increased risk of HIV acquisition. Here the authors longitudinally profile 48 cervicovaginal cytokines and HPV status in a large observational HIV high-risk cohort, and show the same cytokines associate with HPV infection and HIV risk.

    • Lenine J. P. Liebenberg
    • , Lyle R. McKinnon
    • , Nonhlanhla Yende-Zuma
    • , Nigel Garrett
    • , Cheryl Baxter
    • , Ayesha B. M. Kharsany
    • , Derseree Archary
    • , Anne Rositch
    • , Natasha Samsunder
    • , Leila E. Mansoor
    • , Jo-Ann S. Passmore
    • , Salim S. Abdool Karim
    •  & Quarraisha Abdool Karim
  • Article
    | Open Access

    From observational studies, alcohol consumption behaviours are known to be correlated in spouses. Here, Howe et al. use partners’ genotypic information in a Mendelian randomization framework and show that a SNP in the ADH1B gene associates with partner’s alcohol consumption, suggesting that alcohol consumption affects mate choice.

    • Laurence J. Howe
    • , Daniel J. Lawson
    • , Neil M. Davies
    • , Beate St. Pourcain
    • , Sarah J. Lewis
    • , George Davey Smith
    •  & Gibran Hemani
  • Article
    | Open Access

    Pulmonary arterial hypertension (PAH) is characterised by progressive pulmonary vascular remodelling. Here, Arnold et al. develop a therapeutic antibody targeting osteoprotegerin and find it attenuates pulmonary vascular remodelling in multiple rodent models of PAH, alone or in combination with standard of care vasodilator therapy.

    • Nadine D. Arnold
    • , Josephine A. Pickworth
    • , Laura E. West
    • , Sarah Dawson
    • , Joana A. Carvalho
    • , Helen Casbolt
    • , Adam T. Braithwaite
    • , James Iremonger
    • , Lewis Renshall
    • , Volker Germaschewski
    • , Matthew McCourt
    • , Philip Bland-Ward
    • , Hager Kowash
    • , Abdul G. Hameed
    • , Alexander M. K. Rothman
    • , Maria G. Frid
    • , A. A. Roger Thompson
    • , Holly R. Evans
    • , Mark Southwood
    • , Nicholas W. Morrell
    • , David C. Crossman
    • , Moira K. B. Whyte
    • , Kurt R. Stenmark
    • , Christopher M. Newman
    • , David G. Kiely
    • , Sheila E. Francis
    •  & Allan Lawrie
  • Article
    | Open Access

    The risk of fatal stroke is increased in children, adolescent, and young (<40 years) cancer patients after diagnosis. Here, the authors report a retrospective, population-based study and show that the risk of stroke among cancer patients is twice that of the general population and rises with longer follow up time.

    • Nicholas G. Zaorsky
    • , Ying Zhang
    • , Leila T. Tchelebi
    • , Heath B. Mackley
    • , Vernon M. Chinchilli
    •  & Brad E. Zacharia
  • Article
    | Open Access

    Mutations in the chloride channel ClC-2 have been associated with familial forms of hyperaldosteronism. Here, Schewe et al. generated a mouse model carrying the most common mutation found in patients and find it recapitulates key features of the disease, providing a unique tool for future studies on its pathogenesis.

    • Julia Schewe
    • , Eric Seidel
    • , Sofia Forslund
    • , Lajos Marko
    • , Jörg Peters
    • , Dominik N. Muller
    • , Christoph Fahlke
    • , Gabriel Stölting
    •  & Ute Scholl
  • Article
    | Open Access

    The build-up of iron in the body can have serious consequences; current treatment therapies suffer from adverse side effects and toxicity. Here, the authors developed renal clearable nanochelators with improved pharmacodynamics and demonstrated their efficacy and safety in iron overload animal models.

    • Homan Kang
    • , Murui Han
    • , Jie Xue
    • , Yoonji Baek
    • , JuOae Chang
    • , Shuang Hu
    • , HaYoung Nam
    • , Min Joo Jo
    • , Georges El Fakhri
    • , Michael P. Hutchens
    • , Hak Soo Choi
    •  & Jonghan Kim
  • Article
    | Open Access

    Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

    • Raymond Noordam
    • , Maxime M. Bos
    • , Heming Wang
    • , Thomas W. Winkler
    • , Amy R. Bentley
    • , Tuomas O. Kilpeläinen
    • , Paul S. de Vries
    • , Yun Ju Sung
    • , Karen Schwander
    • , Brian E. Cade
    • , Alisa Manning
    • , Hugues Aschard
    • , Michael R. Brown
    • , Han Chen
    • , Nora Franceschini
    • , Solomon K. Musani
    • , Melissa Richard
    • , Dina Vojinovic
    • , Stella Aslibekyan
    • , Traci M. Bartz
    • , Lisa de las Fuentes
    • , Mary Feitosa
    • , Andrea R. Horimoto
    • , Marjan Ilkov
    • , Minjung Kho
    • , Aldi Kraja
    • , Changwei Li
    • , Elise Lim
    • , Yongmei Liu
    • , Dennis O. Mook-Kanamori
    • , Tuomo Rankinen
    • , Salman M. Tajuddin
    • , Ashley van der Spek
    • , Zhe Wang
    • , Jonathan Marten
    • , Vincent Laville
    • , Maris Alver
    • , Evangelos Evangelou
    • , Maria E. Graff
    • , Meian He
    • , Brigitte Kühnel
    • , Leo-Pekka Lyytikäinen
    • , Pedro Marques-Vidal
    • , Ilja M. Nolte
    • , Nicholette D. Palmer
    • , Rainer Rauramaa
    • , Xiao-Ou Shu
    • , Harold Snieder
    • , Stefan Weiss
    • , Wanqing Wen
    • , Lisa R. Yanek
    • , Correa Adolfo
    • , Christie Ballantyne
    • , Larry Bielak
    • , Nienke R. Biermasz
    • , Eric Boerwinkle
    • , Niki Dimou
    • , Gudny Eiriksdottir
    • , Chuan Gao
    • , Sina A. Gharib
    • , Daniel J. Gottlieb
    • , José Haba-Rubio
    • , Tamara B. Harris
    • , Sami Heikkinen
    • , Raphaël Heinzer
    • , James E. Hixson
    • , Georg Homuth
    • , M. Arfan Ikram
    • , Pirjo Komulainen
    • , Jose E. Krieger
    • , Jiwon Lee
    • , Jingmin Liu
    • , Kurt K. Lohman
    • , Annemarie I. Luik
    • , Reedik Mägi
    • , Lisa W. Martin
    • , Thomas Meitinger
    • , Andres Metspalu
    • , Yuri Milaneschi
    • , Mike A. Nalls
    • , Jeff O’Connell
    • , Annette Peters
    • , Patricia Peyser
    • , Olli T. Raitakari
    • , Alex P. Reiner
    • , Patrick C. N. Rensen
    • , Treva K. Rice
    • , Stephen S. Rich
    • , Till Roenneberg
    • , Jerome I. Rotter
    • , Pamela J. Schreiner
    • , James Shikany
    • , Stephen S. Sidney
    • , Mario Sims
    • , Colleen M. Sitlani
    • , Tamar Sofer
    • , Konstantin Strauch
    • , Morris A. Swertz
    • , Kent D. Taylor
    • , André G. Uitterlinden
    • , Cornelia M. van Duijn
    • , Henry Völzke
    • , Melanie Waldenberger
    • , Robert B. Wallance
    • , Ko Willems van Dijk
    • , Caizheng Yu
    • , Alan B. Zonderman
    • , Diane M. Becker
    • , Paul Elliott
    • , Tõnu Esko
    • , Christian Gieger
    • , Hans J. Grabe
    • , Timo A. Lakka
    • , Terho Lehtimäki
    • , Kari E. North
    • , Brenda W. J. H. Penninx
    • , Peter Vollenweider
    • , Lynne E. Wagenknecht
    • , Tangchun Wu
    • , Yong-Bing Xiang
    • , Wei Zheng
    • , Donna K. Arnett
    • , Claude Bouchard
    • , Michele K. Evans
    • , Vilmundur Gudnason
    • , Sharon Kardia
    • , Tanika N. Kelly
    • , Stephen B. Kritchevsky
    • , Ruth J. F. Loos
    • , Alexandre C. Pereira
    • , Mike Province
    • , Bruce M. Psaty
    • , Charles Rotimi
    • , Xiaofeng Zhu
    • , Najaf Amin
    • , L. Adrienne Cupples
    • , Myriam Fornage
    • , Ervin F. Fox
    • , Xiuqing Guo
    • , W. James Gauderman
    • , Kenneth Rice
    • , Charles Kooperberg
    • , Patricia B. Munroe
    • , Ching-Ti Liu
    • , Alanna C. Morrison
    • , Dabeeru C. Rao
    • , Diana van Heemst
    •  & Susan Redline
  • Article
    | Open Access

    DNA-dependent protein kinase (DNA-PK) plays a major role in the DNA damage response upon double-strand break formation. Here, the authors show that the DNA-PK inhibitor AZD7648, enhances the activity of radiotherapy, chemotherapy and the PARP inhibitor olaparib in multiple mouse tumour models.

    • Jacqueline H. L. Fok
    • , Antonio Ramos-Montoya
    • , Mercedes Vazquez-Chantada
    • , Paul W. G. Wijnhoven
    • , Valeria Follia
    • , Neil James
    • , Paul M. Farrington
    • , Ankur Karmokar
    • , Sophie E. Willis
    • , Jonathan Cairns
    • , Jenni Nikkilä
    • , David Beattie
    • , Gillian M. Lamont
    • , M. Raymond V. Finlay
    • , Joanne Wilson
    • , Aaron Smith
    • , Lenka Oplustil O’Connor
    • , Stephanie Ling
    • , Stephen E. Fawell
    • , Mark J. O’Connor
    • , Simon J. Hollingsworth
    • , Emma Dean
    • , Frederick W. Goldberg
    • , Barry R. Davies
    •  & Elaine B. Cadogan
  • Article
    | Open Access

    Predicting the drug response of patients with cancer is crucial for implementing targeted therapy. Here, Su et al. make patient-derived cell lines and perform targeted sequencing and RNA-seq to identify CDKN2A/2B loss as a predictor of response to CDK4/6 inhibitors in esophageal squamous cell carcinoma.

    • Dan Su
    • , Dadong Zhang
    • , Jiaoyue Jin
    • , Lisha Ying
    • , Miao Han
    • , Kaiyan Chen
    • , Bin Li
    • , Junzhou Wu
    • , Zhenghua Xie
    • , Fanrong Zhang
    • , Yihui Lin
    • , Guoping Cheng
    • , Jing-Yu Li
    • , Minran Huang
    • , Jinchao Wang
    • , Kailai Wang
    • , Jianjun Zhang
    • , Fugen Li
    • , Lei Xiong
    • , Andrew Futreal
    •  & Weimin Mao
  • Article
    | Open Access

    Risk of age-related chronic disorders and decrease in resilience is associated with ageing. Here the authors analyse the human blood metabolome and identify metabolites associated with frailty.

    • Nicholas J. W. Rattray
    • , Drupad K. Trivedi
    • , Yun Xu
    • , Tarani Chandola
    • , Caroline H. Johnson
    • , Alan D. Marshall
    • , Krisztina Mekli
    • , Zahra Rattray
    • , Gindo Tampubolon
    • , Bram Vanhoutte
    • , Iain R. White
    • , Frederick C. W. Wu
    • , Neil Pendleton
    • , James Nazroo
    •  & Royston Goodacre
  • Article
    | Open Access

    Here, in a cohort of infants unexposed to maternal antibiotics, the authors analyse the gut microbiome development of children born naturally and by caesarean section, finding a higher abundance of known pathogens in the latter group, and an association between these bacteria and a higher incidence of respiratory infections in the first year of life.

    • Marta Reyman
    • , Marlies A. van Houten
    • , Debbie van Baarle
    • , Astrid A. T. M. Bosch
    • , Wing Ho Man
    • , Mei Ling J. N. Chu
    • , Kayleigh Arp
    • , Rebecca L. Watson
    • , Elisabeth A. M. Sanders
    • , Susana Fuentes
    •  & Debby Bogaert
  • Article
    | Open Access

    Here, Thorsen et al. examine the microbiota during the first three months of life in a cohort of 700 children and find that microbial diversity and the relative abundances of Veillonella and Prevotella in the airways at one month of age are associated with topical immune mediators and asthma by age 6 years.

    • Jonathan Thorsen
    • , Morten A. Rasmussen
    • , Johannes Waage
    • , Martin Mortensen
    • , Asker Brejnrod
    • , Klaus Bønnelykke
    • , Bo L. Chawes
    • , Susanne Brix
    • , Søren J. Sørensen
    • , Jakob Stokholm
    •  & Hans Bisgaard
  • Article
    | Open Access

    Many patients, following therapy for acute myocardial infarction, develop adverse cardiac remodelling. Here the authors present injectable recombinant human collagen 10 of 10 type I and III matrices that are able to limit adverse remodelling and improve function of the myocardium.

    • Sarah McLaughlin
    • , Brian McNeill
    • , James Podrebarac
    • , Katsuhiro Hosoyama
    • , Veronika Sedlakova
    • , Gregory Cron
    • , David Smyth
    • , Richard Seymour
    • , Keshav Goel
    • , Wenbin Liang
    • , Katey J. Rayner
    • , Marc Ruel
    • , Erik J. Suuronen
    •  & Emilio I. Alarcon
  • Article
    | Open Access

    Alterations to the microbiome are now associated with various diseases. Here the authors analyze microbiomes from a large population based cohort and show positive correlations between abundance of Streptococcus spp. and osteoarthritis-related knee pain.

    • Cindy G. Boer
    • , Djawad Radjabzadeh
    • , Carolina Medina-Gomez
    • , Sanzhima Garmaeva
    • , Dieuwke Schiphof
    • , Pascal Arp
    • , Thomas Koet
    • , Alexander Kurilshikov
    • , Jingyuan Fu
    • , M. Arfan Ikram
    • , Sita Bierma-Zeinstra
    • , André G. Uitterlinden
    • , Robert Kraaij
    • , Alexandra Zhernakova
    •  & Joyce B. J. van Meurs
  • Article
    | Open Access

    Rare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals. Here, Oetjens et al. systematically study the contribution of common genetic variation to variable expressivity of RGDs and find it is frequently influenced by polygenic factors identified in genome-wide association studies of relevant traits.

    • M. T. Oetjens
    • , M. A. Kelly
    • , A. C. Sturm
    • , C. L. Martin
    •  & D. H. Ledbetter
  • Article
    | Open Access

    Uterine leiomyomata (UL) or fibroids are neoplasms of the uterine smooth muscle associated with heavy menstrual bleeding and other female reproductive tract morbidity. Here, the authors identify eight previously undescribed genetic loci for UL and further look into genetic overlap with heavy menstrual bleeding and endometriosis.

    • C. S. Gallagher
    • , N. Mäkinen
    • , H. R. Harris
    • , N. Rahmioglu
    • , O. Uimari
    • , J. P. Cook
    • , N. Shigesi
    • , T. Ferreira
    • , D. R. Velez-Edwards
    • , T. L. Edwards
    • , S. Mortlock
    • , Z. Ruhioglu
    • , F. Day
    • , C. M. Becker
    • , V. Karhunen
    • , H. Martikainen
    • , M.-R. Järvelin
    • , R. M. Cantor
    • , P. M. Ridker
    • , K. L. Terry
    • , J. E. Buring
    • , S. D. Gordon
    • , S. E. Medland
    • , G. W. Montgomery
    • , D. R. Nyholt
    • , D. A. Hinds
    • , J. Y. Tung
    • , Michelle Agee
    • , Babak Alipanahi
    • , Adam Auton
    • , Robert K. Bell
    • , Katarzyna Bryc
    • , Sarah L. Elson
    • , Pierre Fontanillas
    • , Nicholas A. Furlotte
    • , 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
    • , Vladimir Vacic
    • , Catherine H. Wilson
    • , J. R. B. Perry
    • , P. A. Lind
    • , J. N. Painter
    • , N. G. Martin
    • , A. P. Morris
    • , D. I. Chasman
    • , S. A. Missmer
    • , K. T. Zondervan
    •  & C. C. Morton
  • Article
    | Open Access

    Senolytic compounds have the ability to eliminate senescent cells from tissues and have been shown to be beneficial in various animal models of age-related diseases. Here the authors show that cardiac glycosides commonly used for heart diseases have senolytic properties in humanized mouse models of tumorigenesis and lung fibrosis.

    • Francisco Triana-Martínez
    • , Pilar Picallos-Rabina
    • , Sabela Da Silva-Álvarez
    • , Federico Pietrocola
    • , Susana Llanos
    • , Verónica Rodilla
    • , Enrica Soprano
    • , Pablo Pedrosa
    • , Alba Ferreirós
    • , Marta Barradas
    • , Fernanda Hernández-González
    • , Marta Lalinde
    • , Neus Prats
    • , Cristina Bernadó
    • , Patricia González
    • , María Gómez
    • , Maria P. Ikonomopoulou
    • , Pablo J. Fernández-Marcos
    • , Tomás García-Caballero
    • , Pablo del Pino
    • , Joaquín Arribas
    • , Anxo Vidal
    • , Miguel González-Barcia
    • , Manuel Serrano
    • , María I. Loza
    • , Eduardo Domínguez
    •  & Manuel Collado
  • Article
    | Open Access

    Monkeys were trained to use an artificial cortico-muscular connection (ACMC) to regain control over a paralyzed hand following subcortical stroke. Control over the paralyzed hand was accompanied by the appearance of localized high-gamma modulation in the cortex, which could be rapidly reset and relocalized to a different cortical site to reactivate motor control.

    • Kenji Kato
    • , Masahiro Sawada
    •  & Yukio Nishimura
  • Article
    | Open Access

    Knottin is a cystine knot peptide. Here, the authors develop a knottin-based tracer for positron emission tomography and demonstrate its ability to detect cancer and idiopathic pulmonary fibrosis through selective binding to integrin αvβ6.

    • Richard H. Kimura
    • , Ling Wang
    • , Bin Shen
    • , Li Huo
    • , Willemieke Tummers
    • , Fabian V. Filipp
    • , Haiwei Henry Guo
    • , Thomas Haywood
    • , Lotfi Abou-Elkacem
    • , Lucia Baratto
    • , Frezghi Habte
    • , Rammohan Devulapally
    • , Timothy H. Witney
    • , Yan Cheng
    • , Suhas Tikole
    • , Subhendu Chakraborti
    • , Jay Nix
    • , Christopher A. Bonagura
    • , Negin Hatami
    • , Joshua J. Mooney
    • , Tushar Desai
    • , Scott Turner
    • , Richard S. Gaster
    • , Andrea Otte
    • , Brendan C. Visser
    • , George A. Poultsides
    • , Jeffrey Norton
    • , Walter Park
    • , Mark Stolowitz
    • , Kenneth Lau
    • , Eric Yang
    • , Arutselvan Natarajan
    • , Ohad Ilovich
    • , Shyam Srinivas
    • , Ananth Srinivasan
    • , Ramasamy Paulmurugan
    • , Juergen Willmann
    • , Frederick T. Chin
    • , Zhen Cheng
    • , Andrei Iagaru
    • , Fang Li
    •  & Sanjiv S. Gambhir
  • Article
    | Open Access

    Extracellular matrix (ECM) is an ideal scaffold for tissue engineering but tends to lack hierarchical structure. Here the authors implant sacrificial templates subcutaneously to build an organised ECM scaffold, and following template removal and decellularisation use these scaffolds to create functionally integrated muscle, nerve and artery in vivo.

    • Meifeng Zhu
    • , Wen Li
    • , Xianhao Dong
    • , Xingyu Yuan
    • , Adam C. Midgley
    • , Hong Chang
    • , Yuhao Wang
    • , Haoyu Wang
    • , Kai Wang
    • , Peter X. Ma
    • , Hongjun Wang
    •  & Deling Kong
  • Article
    | Open Access

    Diagnosing brain cancer is frequently difficult and requires specialist equipment. Here, the authors develop their previous attenuated total reflectance-Fourier transform infrared spectroscopy method and incoporate the use of disposable silicon wafers for diagnosing brain cancer using serum samples.

    • Holly J. Butler
    • , Paul M. Brennan
    • , James M. Cameron
    • , Duncan Finlayson
    • , Mark G. Hegarty
    • , Michael D. Jenkinson
    • , David S. Palmer
    • , Benjamin R. Smith
    •  & Matthew J. Baker
  • Article
    | Open Access

    Here, the authors study the interplay between the microbiome and faecal and blood metabolome, and how the microbiome interacts in the dialogue between these metabolic compartments, identifying a key role for microbial functions and underscoring their relevance for microbiome therapeutic strategies.

    • Alessia Visconti
    • , Caroline I. Le Roy
    • , Fabio Rosa
    • , Niccolò Rossi
    • , Tiphaine C. Martin
    • , Robert P. Mohney
    • , Weizhong Li
    • , Emanuele de Rinaldis
    • , Jordana T. Bell
    • , J. Craig Venter
    • , Karen E. Nelson
    • , Tim D. Spector
    •  & Mario Falchi
  • Article
    | Open Access

    Changes in body mass index (BMI) during infancy and childhood follow a well-characterized pattern. Here, Helgeland et al. perform genome-wide association studies for BMI at 12 time points between birth and 8 years of age and find transient associations at the LEP and LEPR loci.

    • Øyvind Helgeland
    • , Marc Vaudel
    • , Petur B. Juliusson
    • , Oddgeir Lingaas Holmen
    • , Julius Juodakis
    • , Jonas Bacelis
    • , Bo Jacobsson
    • , Haakon Lindekleiv
    • , Kristian Hveem
    • , Rolv Terje Lie
    • , Gun Peggy Knudsen
    • , Camilla Stoltenberg
    • , Per Magnus
    • , Jørn V. Sagen
    • , Anders Molven
    • , Stefan Johansson
    •  & Pål Rasmus Njølstad
  • Article
    | Open Access

    Epitope tags are widely used in various applications, but often lack versatility. Here, the authors introduce a small, alpha helical tag, which is recognized by a high affinity nanobody and can be used in a range of different applications, from protein purification to super-resolution imaging and in vivo detection of proteins.

    • Hansjörg Götzke
    • , Markus Kilisch
    • , Markel Martínez-Carranza
    • , Shama Sograte-Idrissi
    • , Abirami Rajavel
    • , Thomas Schlichthaerle
    • , Niklas Engels
    • , Ralf Jungmann
    • , Pål Stenmark
    • , Felipe Opazo
    •  & Steffen Frey
  • Article
    | Open Access

    Immune-checkpoint inhibition therapy has achieved success in a subset of patients. Here the authors profiled about 200 relevant metabolites in patient serum samples from three independent immunotherapy trials and found the serum kynurenine/tryptophan ratio increases to be associated with worse overall survival.

    • Haoxin Li
    • , Kevin Bullock
    • , Carino Gurjao
    • , David Braun
    • , Sachet A. Shukla
    • , Dominick Bossé
    • , Aly-Khan A. Lalani
    • , Shuba Gopal
    • , Chelsea Jin
    • , Christine Horak
    • , Megan Wind-Rotolo
    • , Sabina Signoretti
    • , David F. McDermott
    • , Gordon J. Freeman
    • , Eliezer M. Van Allen
    • , Stuart L. Schreiber
    • , F. Stephen Hodi
    • , William R. Sellers
    • , Levi A. Garraway
    • , Clary B. Clish
    • , Toni K. Choueiri
    •  & Marios Giannakis
  • Article
    | Open Access

    Prostate cancer progression may be enhanced by a high-fat diet. Here the authors show that a diet high in saturated fats enhance the MYC-driven transcriptional program, a feature that independently predicts prostate cancer progression and death.

    • David P. Labbé
    • , Giorgia Zadra
    • , Meng Yang
    • , Jaime M. Reyes
    • , Charles Y. Lin
    • , Stefano Cacciatore
    • , Ericka M. Ebot
    • , Amanda L. Creech
    • , Francesca Giunchi
    • , Michelangelo Fiorentino
    • , Habiba Elfandy
    • , Sudeepa Syamala
    • , Edward D. Karoly
    • , Mohammed Alshalalfa
    • , Nicholas Erho
    • , Ashley Ross
    • , Edward M. Schaeffer
    • , Ewan A. Gibb
    • , Mandeep Takhar
    • , Robert B. Den
    • , Jonathan Lehrer
    • , R. Jeffrey Karnes
    • , Stephen J. Freedland
    • , Elai Davicioni
    • , Daniel E. Spratt
    • , Leigh Ellis
    • , Jacob D. Jaffe
    • , Anthony V. DʼAmico
    • , Philip W. Kantoff
    • , James E. Bradner
    • , Lorelei A. Mucci
    • , Jorge E. Chavarro
    • , Massimo Loda
    •  & Myles Brown
  • Article
    | Open Access

    There is a lack of human models to study vocal fold epithelia making it difficult to provide therapies for vocal fold disease. Here, the authors generate a human-based model of vocal fold mucosa that mimics in utero development and shows inflammation on exposure to cigarette smoke abstract.

    • Vlasta Lungova
    • , Xia Chen
    • , Ziyue Wang
    • , Christina Kendziorski
    •  & Susan L. Thibeault
  • Article
    | Open Access

    Here, Shah et al. perform a meta-analysis and show that people who live or work in agricultural land in Southeast Asia are on average 1.7 times more likely to be infected with a pathogen than controls, suggesting that agricultural land-use increases infectious disease risk.

    • Hiral A. Shah
    • , Paul Huxley
    • , Jocelyn Elmes
    •  & Kris A. Murray
  • Article
    | Open Access

    The use of PET for detection of Aβ in the brain in AD has limitations; studies also indicate that retinal changes, including Aβ deposition, occur in AD. Here the authors demonstrate the potential to use in vivo retinal hyperspectral imaging as a surrogate for brain accumulation of Aβ.

    • Xavier Hadoux
    • , Flora Hui
    • , Jeremiah K. H. Lim
    • , Colin L. Masters
    • , Alice Pébay
    • , Sophie Chevalier
    • , Jason Ha
    • , Samantha Loi
    • , Christopher J. Fowler
    • , Christopher Rowe
    • , Victor L. Villemagne
    • , Edward N. Taylor
    • , Christopher Fluke
    • , Jean-Paul Soucy
    • , Frédéric Lesage
    • , Jean-Philippe Sylvestre
    • , Pedro Rosa-Neto
    • , Sulantha Mathotaarachchi
    • , Serge Gauthier
    • , Ziad S. Nasreddine
    • , Jean Daniel Arbour
    • , Marc-André Rhéaume
    • , Sylvain Beaulieu
    • , Mohamed Dirani
    • , Christine T. O. Nguyen
    • , Bang V. Bui
    • , Robert Williamson
    • , Jonathan G. Crowston
    •  & Peter van Wijngaarden
  • Article
    | Open Access

    Here, using human cells and mouse models, the authors show that Zika virus can infect preimplantation trophectoderm. Pre-implantation infection can affect nervous system development and survival of neural progenitors, and can result in miscarriage or spontaneous abortion.

    • Lei Tan
    • , Lauretta A. Lacko
    • , Ting Zhou
    • , Delia Tomoiaga
    • , Romulo Hurtado
    • , Tuo Zhang
    • , Ana Sevilla
    • , Aaron Zhong
    • , Christopher E Mason
    • , Scott Noggle
    • , Todd Evans
    • , Heidi Stuhlmann
    • , Robert E. Schwartz
    •  & Shuibing Chen
  • Article
    | Open Access

    Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization. Here, the authors isolate a human monoclonal antibody that binds to a highly conserved epitope on the RSV fusion protein, neutralizes RSV A and B subtypes equipotently and is protective in the cotton rat model.

    • Aimin Tang
    • , Zhifeng Chen
    • , Kara S. Cox
    • , Hua-Poo Su
    • , Cheryl Callahan
    • , Arthur Fridman
    • , Lan Zhang
    • , Sangita B. Patel
    • , Pedro J. Cejas
    • , Ryan Swoyer
    • , Sinoeun Touch
    • , Michael P. Citron
    • , Dhanasekaran Govindarajan
    • , Bin Luo
    • , Michael Eddins
    • , John C. Reid
    • , Stephen M. Soisson
    • , Jennifer Galli
    • , Dai Wang
    • , Zhiyun Wen
    • , Gwendolyn J. Heidecker
    • , Danilo R. Casimiro
    • , Daniel J. DiStefano
    •  & Kalpit A. Vora
  • Article
    | Open Access

    Complex traits associate with genetic variation and environment and their interaction. Here, the authors study the influence of different diets on trait variability in 1154 outbred mice from an advanced intercross line and find gene-diet interactions associated with spontaneous autoimmunity development in these animals.

    • Artem Vorobyev
    • , Yask Gupta
    • , Tanya Sezin
    • , Hiroshi Koga
    • , Yannic C. Bartsch
    • , Meriem Belheouane
    • , Sven Künzel
    • , Christian Sina
    • , Paul Schilf
    • , Heiko Körber-Ahrens
    • , Foteini Beltsiou
    • , Anna Lara Ernst
    • , Stanislav Khil’chenko
    • , Hassanin Al-Aasam
    • , Rudolf A. Manz
    • , Sandra Diehl
    • , Moritz Steinhaus
    • , Joanna Jascholt
    • , Phillip Kouki
    • , Wolf-Henning Boehncke
    • , Tanya N. Mayadas
    • , Detlef Zillikens
    • , Christian D. Sadik
    • , Hiroshi Nishi
    • , Marc Ehlers
    • , Steffen Möller
    • , Katja Bieber
    • , John F. Baines
    • , Saleh M. Ibrahim
    •  & Ralf J. Ludwig
  • Article
    | Open Access

    Functional diversity of tissue-resident macrophages and signals governing their ontogeny and turnover remain unknown for the majority of tissues. Here the authors describe two phenotypically and functionally distinct long-lived populations of lung interstitial macrophages and their putative blood-derived monocytic precursor.

    • Joey Schyns
    • , Qiang Bai
    • , Cecilia Ruscitti
    • , Coraline Radermecker
    • , Sebastiaan De Schepper
    • , Svetoslav Chakarov
    • , Frédéric Farnir
    • , Dimitri Pirottin
    • , Florent Ginhoux
    • , Guy Boeckxstaens
    • , Fabrice Bureau
    •  & Thomas Marichal
  • Article
    | Open Access

    Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.

    • Xueping Liu
    • , Dorte Helenius
    • , Line Skotte
    • , Robin N. Beaumont
    • , Matthias Wielscher
    • , Frank Geller
    • , Julius Juodakis
    • , Anubha Mahajan
    • , Jonathan P. Bradfield
    • , Frederick T. J. Lin
    • , Suzanne Vogelezang
    • , Mariona Bustamante
    • , Tarunveer S. Ahluwalia
    • , Niina Pitkänen
    • , Carol A. Wang
    • , Jonas Bacelis
    • , Maria C. Borges
    • , Ge Zhang
    • , Bruce A. Bedell
    • , Robert M. Rossi
    • , Kristin Skogstrand
    • , Shouneng Peng
    • , Wesley K. Thompson
    • , Vivek Appadurai
    • , Debbie A. Lawlor
    • , Ilkka Kalliala
    • , Christine Power
    • , Mark I. McCarthy
    • , Heather A. Boyd
    • , Mary L. Marazita
    • , Hakon Hakonarson
    • , M. Geoffrey Hayes
    • , Denise M. Scholtens
    • , Fernando Rivadeneira
    • , Vincent W. V. Jaddoe
    • , Rebecca K. Vinding
    • , Hans Bisgaard
    • , Bridget A. Knight
    • , Katja Pahkala
    • , Olli Raitakari
    • , Øyvind Helgeland
    • , Stefan Johansson
    • , Pål R. Njølstad
    • , João Fadista
    • , Andrew J. Schork
    • , Ron Nudel
    • , Daniel E. Miller
    • , Xiaoting Chen
    • , Matthew T. Weirauch
    • , Preben Bo Mortensen
    • , Anders D. Børglum
    • , Merete Nordentoft
    • , Ole Mors
    • , Ke Hao
    • , Kelli K. Ryckman
    • , David M. Hougaard
    • , Leah C. Kottyan
    • , Craig E. Pennell
    • , Leo-Pekka Lyytikainen
    • , Klaus Bønnelykke
    • , Martine Vrijheid
    • , Janine F. Felix
    • , William L. Lowe Jr
    • , Struan F. A. Grant
    • , Elina Hyppönen
    • , Bo Jacobsson
    • , Marjo-Riitta Jarvelin
    • , Louis J. Muglia
    • , Jeffrey C. Murray
    • , Rachel M. Freathy
    • , Thomas M. Werge
    • , Mads Melbye
    • , Alfonso Buil
    •  & Bjarke Feenstra
  • Article
    | Open Access

    Non-invasive methods to predict treatment response are urgently needed. Here in lung cancer, the authors develop a single-cell on-chip cytometry method to metabolically phenotype disseminated tumor cells, revealing metabolic heterogeneity and predictors of therapy response and survival.

    • Ziming Li
    • , Zhuo Wang
    • , Yin Tang
    • , Xiang Lu
    • , Jie Chen
    • , Yu Dong
    • , Baojun Wu
    • , Chunying Wang
    • , Liu Yang
    • , Zhili Guo
    • , Min Xue
    • , Shun Lu
    • , Wei Wei
    •  & Qihui Shi