Physiology

  • Article
    | Open Access

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

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

    White adipose inflammation can occur in obesity and is at least in part mediated by inflammatory immune cells. Here the authors show that the Type I Interferon/Interferon alpha-beta receptor axis promotes an inflammatory, glycolysis associated adipocyte phenotype.

    • Calvin C. Chan
    • , Michelle S. M. A. Damen
    • , Maria E. Moreno-Fernandez
    • , Traci E. Stankiewicz
    • , Monica Cappelletti
    • , Pablo C. Alarcon
    • , Jarren R. Oates
    • , Jessica R. Doll
    • , Rajib Mukherjee
    • , Xiaoting Chen
    • , Rebekah Karns
    • , Matthew T. Weirauch
    • , Michael A. Helmrath
    • , Thomas H. Inge
    •  & Senad Divanovic
  • Article
    | Open Access

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

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

    Mitochondrial dynamics change during ageing, with larger mitochondria and altered protein import in older animals. Here the authors show that Dosmit protein mediates mitochondrial morphology with Rab32 by inducing double-membraned vesicles that regulate protein trafficking into mitochondria.

    • Po-Lin Chen
    • , Kai-Ting Huang
    • , Chu-Ya Cheng
    • , Jian-Chiuan Li
    • , Hsiao-Yen Chan
    • , Tzu-Yang Lin
    • , Matthew P. Su
    • , Wei-Yuan Yang
    • , Henry C. Chang
    • , Horng-Dar Wang
    •  & Chun-Hong Chen
  • Article
    | Open Access

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

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

    Calcium imaging has been used to visualize the activity of individual synapses, but cannot be scaled up to monitor thousands of synapses in tissue. Here, the authors present genetic tools that can be photoconverted from green to red to create a map of active synapses.

    • Alberto Perez-Alvarez
    • , Brenna C. Fearey
    • , Ryan J. O’Toole
    • , Wei Yang
    • , Ignacio Arganda-Carreras
    • , Paul J. Lamothe-Molina
    • , Benjamien Moeyaert
    • , Manuel A. Mohr
    • , Lauren C. Panzera
    • , Christian Schulze
    • , Eric R. Schreiter
    • , J. Simon Wiegert
    • , Christine E. Gee
    • , Michael B. Hoppa
    •  & Thomas G. Oertner
  • Article
    | Open Access

    Senotherapy, the removal of aged T cells, is an effective approach to attenuate age-related diseases. Here the authors report a CD153 targeting vaccine that prevents the accumulation of senescent adipose tissue T cells in mice on high-fat diet, which is associated with improved glucose tolerance.

    • Shota Yoshida
    • , Hironori Nakagami
    • , Hiroki Hayashi
    • , Yuka Ikeda
    • , Jiao Sun
    • , Akiko Tenma
    • , Hideki Tomioka
    • , Tomohiro Kawano
    • , Munehisa Shimamura
    • , Ryuichi Morishita
    •  & Hiromi Rakugi
  • Article
    | Open Access

    The α-cardiac actin M305L hypertrophic cardiomyopathy-causing mutation is located near residues that help confine tropomyosin to an inhibitory position along thin filaments. Here the authors assessed M305L actin in vivo, in vitro, and in silico to characterize emergent pathological properties and define the mechanistic basis of disease.

    • Meera C. Viswanathan
    • , William Schmidt
    • , Peter Franz
    • , Michael J. Rynkiewicz
    • , Christopher S. Newhard
    • , Aditi Madan
    • , William Lehman
    • , Douglas M. Swank
    • , Matthias Preller
    •  & Anthony Cammarato
  • Article
    | Open Access

    The regulatory networks that govern chromatin accessibility and gene expression in brown and beigeadipocytes remain to be fully elucidated. Here the authors use fat-specific inactivation of BAF60a toreveal a differential role for this chromatin remodeling factor in brown fat thermogenesis and coldinduced browning of inguinal fat.

    • Tongyu Liu
    • , Lin Mi
    • , Jing Xiong
    • , Peter Orchard
    • , Qi Yu
    • , Lei Yu
    • , Xu-Yun Zhao
    • , Zhuo-Xian Meng
    • , Stephen C. J. Parker
    • , Jiandie D. Lin
    •  & Siming Li
  • Article
    | Open Access

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

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

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

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

    Structural changes to the left ventricle are characteristic of dilated cardiomyopathy (DCM), a disease for which many rare genetic variants are known. Here, Pirruccello et al. report GWAS of seven cardiac MRI measurements in the left ventricle and describe shared loci and polygenic association with DCM.

    • James P. Pirruccello
    • , Alexander Bick
    • , Minxian Wang
    • , Mark Chaffin
    • , Samuel Friedman
    • , Jie Yao
    • , Xiuqing Guo
    • , Bharath Ambale Venkatesh
    • , Kent D. Taylor
    • , Wendy S. Post
    • , Stephen Rich
    • , Joao A. C. Lima
    • , Jerome I. Rotter
    • , Anthony Philippakis
    • , Steven A. Lubitz
    • , Patrick T. Ellinor
    • , Amit V. Khera
    • , Sekar Kathiresan
    •  & Krishna G. Aragam
  • Article
    | Open Access

    Dysregulated prefrontal control over amygdala has been implicated in the etiology of stress-related psychiatric disorders. Here, the authors show that the dysregulation preferentially occurs in amygdala neurons that are mono- but not bi-directionally connected with dorsomedial prefrontal cortex.

    • Wei-Zhu Liu
    • , Wen-Hua Zhang
    • , Zhi-Heng Zheng
    • , Jia-Xin Zou
    • , Xiao-Xuan Liu
    • , Shou-He Huang
    • , Wen-Jie You
    • , Ye He
    • , Jun-Yu Zhang
    • , Xiao-Dong Wang
    •  & Bing-Xing Pan
  • Article
    | Open Access

    Arterial degeneration, closely associated with cardiovascular diseases, is driven by aging-related vascular cell-specific transcriptomics changes. This study provides a single-cell transcriptomic atlas for senile aortic and coronary arteries and underscores FOXO3A-based the transcriptional network in vasoprotection during aging.

    • Weiqi Zhang
    • , Shu Zhang
    • , Pengze Yan
    • , Jie Ren
    • , Moshi Song
    • , Jingyi Li
    • , Jinghui Lei
    • , Huize Pan
    • , Si Wang
    • , Xibo Ma
    • , Shuai Ma
    • , Hongyu Li
    • , Fei Sun
    • , Haifeng Wan
    • , Wei Li
    • , Piu Chan
    • , Qi Zhou
    • , Guang-Hui Liu
    • , Fuchou Tang
    •  & Jing Qu
  • Article
    | Open Access

    The physiological role of the olfactory marker protein (OMP) has been elusive. Here, the authors demonstrate that OMP buffers cAMP and modulates cAMP-gated channel activity upon sensory stimulation, maintaining neuronal firing during odour-source searching.

    • Noriyuki Nakashima
    • , Kie Nakashima
    • , Akiko Taura
    • , Akiko Takaku-Nakashima
    • , Harunori Ohmori
    •  & Makoto Takano
  • Article
    | Open Access

    Brown adipose tissue, known produce heat by metabolizing fat, is also secretes molecules capable of communicating with other organs. Here the authors show that brown adipose tissue secretes kininogen, a component of heat system regulation, that provides auto-regulatory inhibitory signaling in brown adipose tissue.

    • Marion Peyrou
    • , Rubén Cereijo
    • , Tania Quesada-López
    • , Laura Campderrós
    • , Aleix Gavaldà-Navarro
    • , Laura Liñares-Pose
    • , Elena Kaschina
    • , Thomas Unger
    • , Miguel López
    • , Marta Giralt
    •  & Francesc Villarroya
  • Article
    | Open Access

    Glucose-sensing neurons are found in the ventromedial hypothalamic nucleus (VMH). Here the authors identify the role of estrogen receptor-α expressing neurons in the ventrolateral subdivision of the VMH in sensing hypoglycemia.

    • Yanlin He
    • , Pingwen Xu
    • , Chunmei Wang
    • , Yan Xia
    • , Meng Yu
    • , Yongjie Yang
    • , Kaifan Yu
    • , Xing Cai
    • , Na Qu
    • , Kenji Saito
    • , Julia Wang
    • , Ilirjana Hyseni
    • , Matthew Robertson
    • , Badrajee Piyarathna
    • , Min Gao
    • , Sohaib A. Khan
    • , Feng Liu
    • , Rui Chen
    • , Cristian Coarfa
    • , Zhongming Zhao
    • , Qingchun Tong
    • , Zheng Sun
    •  & Yong Xu
  • Article
    | Open Access

    Hyper-insulinemia associated with excess calorie intake may cause metabolic dysfunction. Here the authors report that mice with partially reduced insulin receptor expression in peripheral tissues are protected from and experience reversal of fatty liver disease.

    • Troy L. Merry
    • , Chris P. Hedges
    • , Stewart W. Masson
    • , Beate Laube
    • , Doris Pöhlmann
    • , Stephan Wueest
    • , Michael E. Walsh
    • , Myrtha Arnold
    • , Wolfgang Langhans
    • , Daniel Konrad
    • , Kim Zarse
    •  & Michael Ristow
  • Article
    | Open Access

    Testing mechanical forces on native molecules in natural environments remains a challenge. Here the authors engineer titin to carry a HaloTag-TEV insertion to allow analysis of dynamics under force in muscle fibers.

    • Jaime Andrés Rivas-Pardo
    • , Yong Li
    • , Zsolt Mártonfalvi
    • , Rafael Tapia-Rojo
    • , Andreas Unger
    • , Ángel Fernández-Trasancos
    • , Elías Herrero-Galán
    • , Diana Velázquez-Carreras
    • , Julio M. Fernández
    • , Wolfgang A. Linke
    •  & Jorge Alegre-Cebollada
  • Article
    | Open Access

    Hepatokines are proteins secreted by the liver that can regulate whole body metabolism. Here the authors identify apolipoprotein J as a hepatokine that regulates muscle glucose metabolism and insulin resistance through a low-density lipoprotein receptor-related protein−2 mediated mechanism in mice.

    • Ji A Seo
    • , Min-Cheol Kang
    • , Won-Mo Yang
    • , Won Min Hwang
    • , Sang Soo Kim
    • , Soo Hyun Hong
    • , Jee-In Heo
    • , Achana Vijyakumar
    • , Leandro Pereira de Moura
    • , Aykut Uner
    • , Hu Huang
    • , Seung Hwan Lee
    • , Inês S. Lima
    • , Kyong Soo Park
    • , Min Seon Kim
    • , Yossi Dagon
    • , Thomas E. Willnow
    • , Vanita Aroda
    • , Theodore P. Ciaraldi
    • , Robert R. Henry
    •  & Young-Bum Kim
  • Article
    | Open Access

    Disruption of different components of molecular circadian clocks has varying effects on health and lifespan of model organisms. Here the authors show that loss of period extends life in drosophila melanogaster.

    • Matt Ulgherait
    • , Anna Chen
    • , Sophie F. McAllister
    • , Han X. Kim
    • , Rebecca Delventhal
    • , Charlotte R. Wayne
    • , Christian J. Garcia
    • , Yocelyn Recinos
    • , Miles Oliva
    • , Julie C. Canman
    • , Martin Picard
    • , Edward Owusu-Ansah
    •  & Mimi Shirasu-Hiza
  • Article
    | Open Access

    Overnutrition is associated with hypothalamic ER stress and impaired leptin signaling. Here the authors show that ER stress already occurs in neonates and that treatment with the ER stress relieving drug TUDCA early in life has beneficial metabolic and neurodevelopmental effects.

    • Soyoung Park
    • , Aleek Aintablian
    • , Berengere Coupe
    •  & Sebastien G. Bouret
  • Article
    | Open Access

    Metabolic remodeling plays an important role in pathological cardiac hypertrophy. Here, the authors show that hexosamine biosynthetic pathway is elevated in the heart by pressure overload, which contributes to heart failure by persistent activation of mTOR.

    • Diem Hong Tran
    • , Herman I. May
    • , Qinfeng Li
    • , Xiang Luo
    • , Jian Huang
    • , Guangyu Zhang
    • , Erica Niewold
    • , Xiaoding Wang
    • , Thomas G. Gillette
    • , Yingfeng Deng
    •  & Zhao V. Wang
  • Article
    | Open Access

    The TrkB receptor is known to regulate obesity via appetite control, but the underlying neural circuits are not known. Here, the authors show that selective modulation of TrkB+ neurons in the paraventricular hypothalamus regulates food intake via circuits to ventromedial hypothalamus and lateral parabrachial nucleus.

    • Juan Ji An
    • , Clint E. Kinney
    • , Ji-Wei Tan
    • , Guey-Ying Liao
    • , Eric J. Kremer
    •  & Baoji Xu
  • Article
    | Open Access

    Cardiovascular risks of cold exposure and the subsequent activation of the β3-AR pathway limit the application of beige fat thermogenesis for the treatment of obesity. Here, the authors show that optogenetics light-activated Ca2+ cycling in adipocytes triggers a fat-specific “cold-mimetic” thermogenesis response protecting mice against diet-induced obesity.

    • Kazuki Tajima
    • , Kenji Ikeda
    • , Yuji Tanabe
    • , Ella A. Thomson
    • , Takeshi Yoneshiro
    • , Yasuo Oguri
    • , Marc D. Ferro
    • , Ada S. Y. Poon
    •  & Shingo Kajimura
  • Article
    | Open Access

    Vitamin D is a precursor of the steroid hormone 1,25-dihydroxyvitamin D3, and its deficiency is associated with many adverse health outcomes. Here, Revez et al. perform a genome-wide association study for circulating 25-hydroxyvitamin D in 417,580 individuals and test for potential causal relationships with other traits using Mendelian randomization.

    • Joana A. Revez
    • , Tian Lin
    • , Zhen Qiao
    • , Angli Xue
    • , Yan Holtz
    • , Zhihong Zhu
    • , Jian Zeng
    • , Huanwei Wang
    • , Julia Sidorenko
    • , Kathryn E. Kemper
    • , Anna A. E. Vinkhuyzen
    • , Julanne Frater
    • , Darryl Eyles
    • , Thomas H. J. Burne
    • , Brittany Mitchell
    • , Nicholas G. Martin
    • , Gu Zhu
    • , Peter M. Visscher
    • , Jian Yang
    • , Naomi R. Wray
    •  & John J. McGrath
  • Article
    | Open Access

    Acellular tissue engineered vessels functionalised with VEGF are coated with a layer of endothelial cells after in vivo implantation, but the source of the cells are unknown. Here the authors provide evidence that monocytes expressing VEGF receptors can transdifferentiate into endothelial cells via a macrophage intermediate.

    • Randall J. Smith Jr.
    • , Bita Nasiri
    • , Julien Kann
    • , Donald Yergeau
    • , Jonathan E. Bard
    • , Daniel D. Swartz
    •  & Stelios T. Andreadis
  • Article
    | Open Access

    The molecular basis of activin receptor-like kinase 1 (ALK1)-mediated endothelial bone morphogenetic protein (BMP) signalling is not fully understood. Here, the authors present crystal structures of the BMP10:ALK1 and prodomain-bound BMP9:ALK1 complexes, providing mechanistic insights into ALK1 signalling specificity.

    • Richard M. Salmon
    • , Jingxu Guo
    • , Jennifer H. Wood
    • , Zhen Tong
    • , John S. Beech
    • , Aleksandra Lawera
    • , Minmin Yu
    • , David J. Grainger
    • , Jill Reckless
    • , Nicholas W. Morrell
    •  & Wei Li
  • Article
    | Open Access

    Exercise has been shown to be an effective approach to ameliorate metabolic disease in mice housed at ambient temperatures, a condition of mild cold stress to mice. Here the authors show that molecular and metabolic adaptations to exercise are blunted when mice are housed in thermoneutral conditions.

    • Steffen H. Raun
    • , Carlos Henriquez-Olguín
    • , Iuliia Karavaeva
    • , Mona Ali
    • , Lisbeth L. V. Møller
    • , Witold Kot
    • , Josué L. Castro-Mejía
    • , Dennis Sandris Nielsen
    • , Zachary Gerhart-Hines
    • , Erik A. Richter
    •  & Lykke Sylow
  • Article
    | Open Access

    Aging involves gradual loss of tissue function, and transcription factor (TF) expression can ameliorate this in progeroid mice. Here the authors show that transient TF expression reverses age-associated epigenetic marks, inflammatory profiles and restores regenerative potential in naturally aged human cells.

    • Tapash Jay Sarkar
    • , Marco Quarta
    • , Shravani Mukherjee
    • , Alex Colville
    • , Patrick Paine
    • , Linda Doan
    • , Christopher M. Tran
    • , Constance R. Chu
    • , Steve Horvath
    • , Lei S. Qi
    • , Nidhi Bhutani
    • , Thomas A. Rando
    •  & Vittorio Sebastiano
  • 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

    Leptin regulates the sympathetic nervous system, energy expenditure and body weight through incompletely understood mechanisms. Here the authors report that Sh2b1 in leptin receptor positive neurons mediates the ability of leptin to stimulate sympathetic nerve activity in brown adipose tissue, body temperature and cold tolerance.

    • Lin Jiang
    • , Haoran Su
    • , Xiaoyin Wu
    • , Hong Shen
    • , Min-Hyun Kim
    • , Yuan Li
    • , Martin G. Myers Jr
    • , Chung Owyang
    •  & Liangyou Rui
  • Article
    | Open Access

    Genetic variants in the FAM13A locus have been associated with anthropometric and glycemic traits. Here, using fine-mapping, in vitro knockdown studies in pre-adipocytes and in vivo knockout in mice, the authors show that FAM13A is involved in regulating fat distribution and metabolic traits.

    • Mohsen Fathzadeh
    • , Jiehan Li
    • , Abhiram Rao
    • , Naomi Cook
    • , Indumathi Chennamsetty
    • , Marcus Seldin
    • , Xiang Zhou
    • , Panjamaporn Sangwung
    • , Michael J. Gloudemans
    • , Mark Keller
    • , Allan Attie
    • , Jing Yang
    • , Martin Wabitsch
    • , Ivan Carcamo-Orive
    • , Yuko Tada
    • , Aldons J. Lusis
    • , Myung Kyun Shin
    • , Cliona M. Molony
    • , Tracey McLaughlin
    • , Gerald Reaven
    • , Stephen B. Montgomery
    • , Dermot Reilly
    • , Thomas Quertermous
    • , Erik Ingelsson
    •  & Joshua W. Knowles
  • Article
    | Open Access

    Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue. Here the authors show that FGF6 and FGF9 induce UCP1 expression in adipocytes and preadipocytes, via modulation of a transcriptional network that is dissociated from brown adipogenesis.

    • Farnaz Shamsi
    • , Ruidan Xue
    • , Tian Lian Huang
    • , Morten Lundh
    • , Yang Liu
    • , Luiz O. Leiria
    • , Matthew D. Lynes
    • , Elena Kempf
    • , Chih-Hao Wang
    • , Satoru Sugimoto
    • , Pasquale Nigro
    • , Kathrin Landgraf
    • , Tim Schulz
    • , Yiming Li
    • , Brice Emanuelli
    • , Srinivas Kothakota
    • , Lewis T. Williams
    • , Niels Jessen
    • , Steen Bønløkke Pedersen
    • , Yvonne Böttcher
    • , Matthias Blüher
    • , Antje Körner
    • , Laurie J. Goodyear
    • , Moosa Mohammadi
    • , C. Ronald Kahn
    •  & Yu-Hua Tseng
  • Article
    | Open Access

    The physiological roles of the Golgi reassembly-stacking protein 55 (GRASP55/GORASP55) remain largely elusive. Here, the authors show that the Golgi-resident protein GRASP55 plays a crucial role in lipid homeostasis by regulating intestinal lipid uptake.

    • Jiyoon Kim
    • , Hyeyon Kim
    • , Shin Hye Noh
    • , Dong Geon Jang
    • , Shi-Young Park
    • , Dongkook Min
    • , Hyunki Kim
    • , Hee-Seok Kweon
    • , Hoguen Kim
    • , Sowon Aum
    • , Sookyung Seo
    • , Cheol Soo Choi
    • , Hail Kim
    • , Jae Woo Kim
    • , Seok Jun Moon
    • , Heon Yung Gee
    •  & Min Goo Lee
  • Article
    | Open Access

    Most gene-by-environment interaction methods rely on the availability of the interacting environment. Here, the authors propose a robust maximum likelihood method for estimating the overall statistical interaction between a genetic risk score for a continuous outcome and all environmental variables.

    • Jonathan Sulc
    • , Ninon Mounier
    • , Felix Günther
    • , Thomas Winkler
    • , Andrew R. Wood
    • , Timothy M. Frayling
    • , Iris M. Heid
    • , Matthew R. Robinson
    •  & Zoltán Kutalik
  • Article
    | Open Access

    In infants, superiority of semantic over episodic memory formation has been postulated. Here, authors show that both types of memory coexist in one-year-olds, with consolidation during sleep affecting whether an experienced event is recognized as a detailed episode or as general semantic knowledge.

    • Manuela Friedrich
    • , Matthias Mölle
    • , Angela D. Friederici
    •  & Jan Born
  • Article
    | Open Access

    Genome-scale models of microbial metabolism largely ignore reaction kinetics. Here, the authors develop a general mathematical framework for modeling cellular growth with explicit non-linear reaction kinetics and use it to glean insights into the principles of cellular resource allocation and growth.

    • Hugo Dourado
    •  & Martin J. Lercher
  • Article
    | Open Access

    The roots of psychopathology take shape during adverse parent-infant interactions, shown through infant attachment quality. Using rodents, the authors show that blunted infant cortical processing of the mother determines attachment quality through a stress hormone-dependent mechanism.

    • Maya Opendak
    • , Emma Theisen
    • , Anna Blomkvist
    • , Kaitlin Hollis
    • , Teresa Lind
    • , Emma Sarro
    • , Johan N. Lundström
    • , Nim Tottenham
    • , Mary Dozier
    • , Donald A. Wilson
    •  & Regina M. Sullivan
  • Article
    | Open Access

    Interaural timing and level differences had been considered the two important cues for horizontal sound localization. Here, the authors show that the third cue, spectral information, plays an essential role in the encoding of the azimuthal auditory map in the mouse superior colliculus.

    • Shinya Ito
    • , Yufei Si
    • , David A. Feldheim
    •  & Alan M. Litke
  • Article
    | Open Access

    Phosphocreatine plays a vital role in cellular energetic homeostasis, but there are no routine diagnostic tests to noninvasively map the distribution with clinically relevant spatial resolution. Here, the authors develop and validate a noninvasive approach for quantifying and imaging phosphocreatine, without contrast agents, on widely available clinical MRI scanners with artificial neural networks.

    • Lin Chen
    • , Michael Schär
    • , Kannie W. Y. Chan
    • , Jianpan Huang
    • , Zhiliang Wei
    • , Hanzhang Lu
    • , Qin Qin
    • , Robert G. Weiss
    • , Peter C. M. van Zijl
    •  & Jiadi Xu
  • Article
    | Open Access

    Because of stochastic connections between some brain regions, an identified neuron can receive different inputs across individual animals and yet respond similarly to sensory stimuli. Here the authors reveal the network mechanisms that enable stereotypic sensory responses across individuals.

    • Aarush Mohit Mittal
    • , Diksha Gupta
    • , Amrita Singh
    • , Andrew C. Lin
    •  & Nitin Gupta
  • Article
    | Open Access

    Heterogeneous nuclear ribonucleoproteins (hnRNPs) play critical roles in the biogenesis, localization and transport of RNA. Here authors investigate a role for hnRNPs in sterol metabolism in mice and provide insights into their role in selective promoter activation.

    • Zhengyi Zhang
    • , An-Chieh Feng
    • , David Salisbury
    • , Xin Liu
    • , Xiaohui Wu
    • , Jason Kim
    • , Irina Lapina
    • , Dan Wang
    • , Brennan Lee
    • , Josue Fraga
    • , Calvin Pan
    • , Kevin J. Williams
    • , Aldons J. Lusis
    • , Phil Scumpia
    •  & Tamer Sallam
  • Article
    | Open Access

    Metabolic adaptation to different diets results in changes to gene expression. Here, the authors characterise the chromatin landscape and transcriptional network in mice on a diet of high saturated fat, compared to a diet high in carbohydrate, finding a dramatic reprogramming of the liver transcriptional network.

    • Yufeng Qin
    • , Sara A. Grimm
    • , John D. Roberts
    • , Kaliopi Chrysovergis
    •  & Paul A. Wade
  • Article
    | Open Access

    In response to insulin, liver cells increase de novo lipogenesis via the transcription factors USF-1 and SREBP. Here the authors show that USF-1 recruits JMJD1C, after its phosphorylation by mTOR, to lipogenic promoters where JMJD1C demethylates histone H3, contributing to lipogenesis by an epigenetic mechanism.

    • Jose A. Viscarra
    • , Yuhui Wang
    • , Hai P. Nguyen
    • , Yoon Gi Choi
    •  & Hei Sook Sul
  • Article
    | Open Access

    Ammonia oxidizing archaea and Nitrospinae are the main known nitrifiers in the ocean, but the much greater abundance of the former is puzzling. Here, the authors show that differences in mortality, rather than thermodynamics, cell size or biomass yield, explain the discrepancy, without the need to invoke yet undiscovered, abundant nitrite oxidizers.

    • Katharina Kitzinger
    • , Hannah K. Marchant
    • , Laura A. Bristow
    • , Craig W. Herbold
    • , Cory C. Padilla
    • , Abiel T. Kidane
    • , Sten Littmann
    • , Holger Daims
    • , Petra Pjevac
    • , Frank J. Stewart
    • , Michael Wagner
    •  & Marcel M. M. Kuypers
  • Article
    | Open Access

    Whether the immune system aging differs between men and women is barely known. Here the authors characterize gene expression, chromatin state and immune subset composition in the blood of healthy humans 22 to 93 years of age, uncovering shared as well as sex-unique alterations, and create a web resource to interactively explore the data.

    • Eladio J. Márquez
    • , Cheng-han Chung
    • , Radu Marches
    • , Robert J. Rossi
    • , Djamel Nehar-Belaid
    • , Alper Eroglu
    • , David J. Mellert
    • , George A. Kuchel
    • , Jacques Banchereau
    •  & Duygu Ucar
  • Article
    | Open Access

    Extracellular vesicles (EVs) containing miRNAs or proteins can coordinate metabolic responses between tissues. Here the authors demonstrate that during lipid overload, the liver secretes miRNA-containing EVs through a Ggpps-Rab27 dependent mechanism, which controls adipose tissue lipid storage capacity.

    • Yue Zhao
    • , Meng-Fei Zhao
    • , Shan Jiang
    • , Jing Wu
    • , Jia Liu
    • , Xian-Wen Yuan
    • , Di Shen
    • , Jing-Zi Zhang
    • , Nan Zhou
    • , Jian He
    • , Lei Fang
    • , Xi-Tai Sun
    • , Bin Xue
    •  & Chao-Jun Li
  • Article
    | Open Access

    Production of inflammatory mediators by M1-polarized macrophages is thought to rely on suppression of mitochondrial metabolism in favor of glycolysis. Refining this concept, here the authors define metabolic targets of nitric oxide as responsible for the mitochondrial rewiring resulting from polarization.

    • Erika M. Palmieri
    • , Marieli Gonzalez-Cotto
    • , Walter A. Baseler
    • , Luke C. Davies
    • , Bart Ghesquière
    • , Nunziata Maio
    • , Christopher M. Rice
    • , Tracey A. Rouault
    • , Teresa Cassel
    • , Richard M. Higashi
    • , Andrew N. Lane
    • , Teresa W.-M. Fan
    • , David A. Wink
    •  & Daniel W. McVicar