Signs and symptoms

  • Article
    | Open Access

    Snoring is common in the population and tends to be more prevalent in older and/or male individuals. Here, the authors perform GWAS for habitual snoring, identify 41 genomic loci and explore potential causal relationships with anthropometric and cardiometabolic disease traits.

    • Adrián I. Campos
    • , Luis M. García-Marín
    • , Enda M. Byrne
    • , Nicholas G. Martin
    • , Gabriel Cuéllar-Partida
    •  & Miguel E. Rentería
  • 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

    Our experience of pain can be affected by our expectations about how much pain we will feel. Here, the authors show that both social information-driven expectations, and those based on personal experience, are both able to modulate pain, but by different neural pathways.

    • Leonie Koban
    • , Marieke Jepma
    • , Marina López-Solà
    •  & Tor D. Wager
  • 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

    Fibrosis is a hallmark of several cardiac pathologies and its underlying mechanisms are still poorly defined. Here the authors show that macrophage hypoxia signaling following transverse aortic constriction in mice suppresses the activation of cardiac fibroblasts by secreting oncostatin M.

    • Hajime Abe
    • , Norihiko Takeda
    • , Takayuki Isagawa
    • , Hiroaki Semba
    • , Satoshi Nishimura
    • , Masaki Suimye Morioka
    • , Yu Nakagama
    • , Tatsuyuki Sato
    • , Katsura Soma
    • , Katsuhiro Koyama
    • , Masaki Wake
    • , Manami Katoh
    • , Masataka Asagiri
    • , Michael L. Neugent
    • , Jung-whan Kim
    • , Christian Stockmann
    • , Tomo Yonezawa
    • , Ryo Inuzuka
    • , Yasushi Hirota
    • , Koji Maemura
    • , Takeshi Yamashita
    • , Kinya Otsu
    • , Ichiro Manabe
    • , Ryozo Nagai
    •  & Issei Komuro
  • Article
    | Open Access

    People vary in the extent to which they feel better after taking an inert, placebo, treatment, but the basis for individual placebo response is unclear. Here, the authors show how brain structural and functional variables, as well as personality traits, predict placebo response in those with chronic back pain.

    • Etienne Vachon-Presseau
    • , Sara E. Berger
    • , Taha B. Abdullah
    • , Lejian Huang
    • , Guillermo A. Cecchi
    • , James W. Griffith
    • , Thomas J. Schnitzer
    •  & A. Vania Apkarian
  • Article
    | Open Access

    Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow and gut microbiota. Here, the authors show that chronic hypoxia predisposes bone marrow stem cells to premature senescence, which may be due to gut dysbiosis and gut microbiota-derived d-galactose accumulation.

    • Junyue Xing
    • , Yongquan Ying
    • , Chenxi Mao
    • , Yiwei Liu
    • , Tingting Wang
    • , Qian Zhao
    • , Xiaoling Zhang
    • , Fuxia Yan
    •  & Hao Zhang
  • Article
    | Open Access

    Hyperoxia contributes to lung injury in bronchopulmonary dysplasia. The authors show that hyperoxia increases miR-34a expression in human neonates and in mouse models, and that pathology is ameliorated by miR-34a inhibition or by administration of its target angiopoietin-1

    • Mansoor Syed
    • , Pragnya Das
    • , Aishwarya Pawar
    • , Zubair H. Aghai
    • , Anu Kaskinen
    • , Zhen W. Zhuang
    • , Namasivayam Ambalavanan
    • , Gloria Pryhuber
    • , Sture Andersson
    •  & Vineet Bhandari
  • Article
    | Open Access

    Removal of senescent cells rejuvenates lungs of aged mice. Here the authors show that elimination of senescent cells using either genetic or pharmacological means improves lung function and physical health in a mouse model of idiopathic pulmonary fibrosis (IPF), suggesting potential therapy for treatment of human IPF.

    • Marissa J. Schafer
    • , Thomas A. White
    • , Koji Iijima
    • , Andrew J. Haak
    • , Giovanni Ligresti
    • , Elizabeth J. Atkinson
    • , Ann L. Oberg
    • , Jodie Birch
    • , Hanna Salmonowicz
    • , Yi Zhu
    • , Daniel L. Mazula
    • , Robert W. Brooks
    • , Heike Fuhrmann-Stroissnigg
    • , Tamar Pirtskhalava
    • , Y. S. Prakash
    • , Tamara Tchkonia
    • , Paul D. Robbins
    • , Marie Christine Aubry
    • , João F. Passos
    • , James L. Kirkland
    • , Daniel J. Tschumperlin
    • , Hirohito Kita
    •  & Nathan K. LeBrasseur
  • Article
    | Open Access

    Patients with diabetes often have delayed wound healing, associated with excessive inflammation. Here the authors report that REG3A inhibits TLR3-driven inflammation in skin wounds, and show that REG3A is reduced in models of diabetes, which exacerbates inflammation in diabetic wounds.

    • Yelin Wu
    • , Yanchun Quan
    • , Yuanqi Liu
    • , Keiwei Liu
    • , Hongquan Li
    • , Ziwei Jiang
    • , Tian Zhang
    • , Hu Lei
    • , Katherine A. Radek
    • , Dongqing Li
    • , Zhenhua Wang
    • , Jilong Lu
    • , Wang Wang
    • , Shizhao Ji
    • , Zhaofan Xia
    •  & Yuping Lai
  • Article
    | Open Access

    The presence of the signalling lipid Sphingosine 1-phosphate (S1P) in erythrocytes has unclear physiological implications. Here the authors show that the S1P-generating enzyme Sphingosine kinase type 1 and its product S1P play an important role in the red blood cell adaptation to hypoxic environments in mice and humans.

    • Kaiqi Sun
    • , Yujin Zhang
    • , Angelo D’Alessandro
    • , Travis Nemkov
    • , Anren Song
    • , Hongyu Wu
    • , Hong Liu
    • , Morayo Adebiyi
    • , Aji Huang
    • , Yuan E. Wen
    • , Mikhail V. Bogdanov
    • , Alejandro Vila
    • , John O’Brien
    • , Rodney E. Kellems
    • , William Dowhan
    • , Andrew W. Subudhi
    • , Sonja Jameson-Van Houten
    • , Colleen G. Julian
    • , Andrew T. Lovering
    • , Martin Safo
    • , Kirk C. Hansen
    • , Robert C. Roach
    •  & Yang Xia
  • Article
    | Open Access

    The etiology of focal cortical dysplasia (FCD) is not fully understood. Here authors generate an mTORC1 overactivation mouse model that recapitulates hallmarks of type II FCDs, including spontaneous seizures, and suggest that neuronal defects, rather than macrostructural changes, lead to seizures.

    • Lawrence S. Hsieh
    • , John H. Wen
    • , Kumiko Claycomb
    • , Yuegao Huang
    • , Felicia A. Harrsch
    • , Janice R. Naegele
    • , Fahmeed Hyder
    • , Gordon F. Buchanan
    •  & Angelique Bordey
  • Article
    | Open Access

    Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. Here, the authors show that caveolin-1 can down-regulate global membrane protein endocytosis in hypoxic cells with potential implications for targeting the hypoxic 3microenvironment of aggressive tumours.

    • E. Bourseau-Guilmain
    • , J. A. Menard
    • , E. Lindqvist
    • , V. Indira Chandran
    • , H. C. Christianson
    • , M. Cerezo Magaña
    • , J. Lidfeldt
    • , G. Marko-Varga
    • , C. Welinder
    •  & M. Belting
  • Article
    | Open Access

    The development of asthma following eczema is known as the atopic march. Here the authors conduct a GWAS on affected children and identify two novel loci associated with the disease phenotype.

    • Ingo Marenholz
    • , Jorge Esparza-Gordillo
    • , Franz Rüschendorf
    • , Anja Bauerfeind
    • , David P. Strachan
    • , Ben D. Spycher
    • , Hansjörg Baurecht
    • , Patricia Margaritte-Jeannin
    • , Annika Sääf
    • , Marjan Kerkhof
    • , Markus Ege
    • , Svetlana Baltic
    • , Melanie C. Matheson
    • , Jin Li
    • , Sven Michel
    • , Wei Q. Ang
    • , Wendy McArdle
    • , Andreas Arnold
    • , Georg Homuth
    • , Florence Demenais
    • , Emmanuelle Bouzigon
    • , Cilla Söderhäll
    • , Göran Pershagen
    • , Johan C. de Jongste
    • , Dirkje S. Postma
    • , Charlotte Braun-Fahrländer
    • , Elisabeth Horak
    • , Ludmila M. Ogorodova
    • , Valery P. Puzyrev
    • , Elena Yu Bragina
    • , Thomas J. Hudson
    • , Charles Morin
    • , David L. Duffy
    • , Guy B. Marks
    • , Colin F. Robertson
    • , Grant W. Montgomery
    • , Bill Musk
    • , Philip J. Thompson
    • , Nicholas G. Martin
    • , Alan James
    • , Patrick Sleiman
    • , Elina Toskala
    • , Elke Rodriguez
    • , Regina Fölster-Holst
    • , Andre Franke
    • , Wolfgang Lieb
    • , Christian Gieger
    • , Andrea Heinzmann
    • , Ernst Rietschel
    • , Thomas Keil
    • , Sven Cichon
    • , Markus M. Nöthen
    • , Craig E. Pennell
    • , Peter D. Sly
    • , Carsten O. Schmidt
    • , Anja Matanovic
    • , Valentin Schneider
    • , Matthias Heinig
    • , Norbert Hübner
    • , Patrick G. Holt
    • , Susanne Lau
    • , Michael Kabesch
    • , Stefan Weidinger
    • , Hakon Hakonarson
    • , Manuel A. R. Ferreira
    • , Catherine Laprise
    • , Maxim B. Freidin
    • , Jon Genuneit
    • , Gerard H. Koppelman
    • , Erik Melén
    • , Marie- Hélène Dizier
    • , A John Henderson
    •  & Young Ae Lee
  • Article
    | Open Access

    Stiffness in the extracellular matrix is thought to contribute to pathological cutaneous fibrosis. Here, the authors identify the elastic fibre protein Fibulin-5 as a link and potential therapeutic target mediating the transition of cutaneous stiffening to fibrosis.

    • Manando Nakasaki
    • , Yongsung Hwang
    • , Yun Xie
    • , Sunny Kataria
    • , Rupali Gund
    • , Edries Y. Hajam
    • , Rekha Samuel
    • , Renu George
    • , Debashish Danda
    • , Paul M.J.
    • , Tomoyuki Nakamura
    • , Zhouxin Shen
    • , Steve Briggs
    • , Shyni Varghese
    •  & Colin Jamora
  • Article |

    Sensory neurons that mediate histamine-independent itch express Mas-related G protein coupled receptors (Mrgprs). Here, Reddy et al.show that the cysteine protease cathepsin S cleaves and activates MrgpcrC11 without the generation of a tethered ligand, in contrast to other protease activated receptors.

    • Vemuri B. Reddy
    • , Shuohao Sun
    • , Ehsan Azimi
    • , Sarina B. Elmariah
    • , Xinzhong Dong
    •  & Ethan A. Lerner
  • Article |

    Aortic dissection and intramural haematoma are caused by separation of the aortic wall via an unknown mechanism. Here the authors show that the inflammatory cytokine, granulocyte macrophage colony-stimulating factor, is a central regulatory molecule causative of these conditions in mice and humans.

    • Bo-Kyung Son
    • , Daigo Sawaki
    • , Shota Tomida
    • , Daishi Fujita
    • , Kenichi Aizawa
    • , Hiroki Aoki
    • , Masahiro Akishita
    • , Ichiro Manabe
    • , Issei Komuro
    • , Scott L. Friedman
    • , Ryozo Nagai
    •  & Toru Suzuki
  • Article |

    Sustained pressure on the skin reduces blood flow and causes wounds. Here the authors describe a flexible electronic ‘bandage’ that measures changes in tissue impedance spectra and detects early tissue damage in rats before it can be visualized, thus enabling possible prevention of pressure ulcers.

    • Sarah L. Swisher
    • , Monica C. Lin
    • , Amy Liao
    • , Elisabeth J. Leeflang
    • , Yasser Khan
    • , Felippe J. Pavinatto
    • , Kaylee Mann
    • , Agne Naujokas
    • , David Young
    • , Shuvo Roy
    • , Michael R. Harrison
    • , Ana Claudia Arias
    • , Vivek Subramanian
    •  & Michel M. Maharbiz
  • Article
    | Open Access

    Use of aromatase inhibitors for breast cancer therapy is associated with severe pain symptoms, the underlying mechanism of which is unknown. Here the authors show that in mice, TRPA1 is a major mediator of the proinflammatory and proalgesic actions of aromatase inhibitors.

    • Camilla Fusi
    • , Serena Materazzi
    • , Silvia Benemei
    • , Elisabetta Coppi
    • , Gabriela Trevisan
    • , Ilaria M. Marone
    • , Daiana Minocci
    • , Francesco De Logu
    • , Tiziano Tuccinardi
    • , Maria Rosaria Di Tommaso
    • , Tommaso Susini
    • , Gloriano Moneti
    • , Giuseppe Pieraccini
    • , Pierangelo Geppetti
    •  & Romina Nassini
  • Article |

    Unravelling the relationships between disease symptoms and underlying molecular origins is an important task in biomedical research. Here, Zhou et al.link diseases via their symptom overlap, and show that similar phenotypes are mirrored in networks that connect diseases with common genes or protein interactions.

    • XueZhong Zhou
    • , Jörg Menche
    • , Albert-László Barabási
    •  & Amitabh Sharma
  • Article
    | Open Access

    The signalling cascade involved in lung ischaemia–reperfusion-induced oedema is poorly understood. Using knockout mice, Weissmannet al. propose a model in which reactive oxygen species production by endothelial NOX2 leads to phospholipase C-γ activation, DAG kinase inhibition and subsequent TRPC6 activation.

    • Norbert Weissmann
    • , Akylbek Sydykov
    • , Hermann Kalwa
    • , Ursula Storch
    • , Beate Fuchs
    • , Michael Mederos y Schnitzler
    • , Ralf P. Brandes
    • , Friedrich Grimminger
    • , Marcel Meissner
    • , Marc Freichel
    • , Stefan Offermanns
    • , Florian Veit
    • , Oleg Pak
    • , Karl-Heinz Krause
    • , Ralph T. Schermuly
    • , Alison C Brewer
    • , Harald H.H.W. Schmidt
    • , Werner Seeger
    • , Ajay M. Shah
    • , Thomas Gudermann
    • , Hossein A. Ghofrani
    •  & Alexander Dietrich