Physiology

  • Article | | open

    SUMOylation is known to regulate androgen receptor (AR) activity in cultured cells. Here, using SUMOylation-deficient AR knock-in mice, the authors demonstrate that SUMOylation is required for AR-related gene expression specifically in the epididymal tissues, but not the testis.

    • Fu-Ping Zhang
    • , Marjo Malinen
    • , Arfa Mehmood
    • , Tiina Lehtiniemi
    • , Tiina Jääskeläinen
    • , Einari A. Niskanen
    • , Hanna Korhonen
    • , Asta Laiho
    • , Laura L. Elo
    • , Claes Ohlsson
    • , Noora Kotaja
    • , Matti Poutanen
    • , Petra Sipilä
    •  & Jorma J. Palvimo
  • Article | | open

    Immune cells produce reactive oxygen species (ROS) to eliminate pathogens, but cell-spontaneous death and ageing may also be induced. Here the authors show that, upon sensing ROS, Mst1/2 kinases modulate the activity of Nrf2 transcription factor and downstream genetic programs to protect mouse macrophages from death and ageing.

    • Ping Wang
    • , Jing Geng
    • , Jiahui Gao
    • , Hao Zhao
    • , Junhong Li
    • , Yiran Shi
    • , Bingying Yang
    • , Chen Xiao
    • , Yueyue Linghu
    • , Xiufeng Sun
    • , Xin Chen
    • , Lixin Hong
    • , Funiu Qin
    • , Xun Li
    • , Jau-Song Yu
    • , Han You
    • , Zengqiang Yuan
    • , Dawang Zhou
    • , Randy L. Johnson
    •  & Lanfen Chen
  • Article | | open

    Calcium signalling downstream of VEGF is essential for VEGF-induced angiogenesis. Here Savage et al. show that Transmembrane Protein 33 (TMEM33) is required for angiogenesis and the endothelial calcium response to VEGF, revealing a function for TMEM33 in multicellular organisms.

    • Aaron M. Savage
    • , Sathishkumar Kurusamy
    • , Yan Chen
    • , Zhen Jiang
    • , Karishma Chhabria
    • , Ryan B. MacDonald
    • , Hyejeong R. Kim
    • , Heather L. Wilson
    • , Fredericus J. M. van Eeden
    • , Angel L. Armesilla
    • , Timothy J. A. Chico
    •  & Robert N. Wilkinson
  • Article | | open

    The mechanistic target of rapamycin (TOR) functions as an energy sensor and contributes to the control of glucose homeostasis. Here, the authors show that mTOR in the upper small intestine regulates hepatic glucose production and is required for the glucose lowering effect of metformin.

    • T. M. Zaved Waise
    • , Mozhgan Rasti
    • , Frank A. Duca
    • , Song-Yang Zhang
    • , Paige V. Bauer
    • , Christopher J. Rhodes
    •  & Tony K. T. Lam
  • Article | | open

    Reduction in food intake elicits neuroendocrine adaptations to counterregulate the negative energy balance, e.g. via reduction in leptin levels. Here, the authors identify an additional starvation signal, growth hormone (GH). Blocking GH receptor attenuates the fall of whole body energy expenditure during food deprivation in mice.

    • Isadora C. Furigo
    • , Pryscila D. S. Teixeira
    • , Gabriel O. de Souza
    • , Gisele C. L. Couto
    • , Guadalupe García Romero
    • , Mario Perelló
    • , Renata Frazão
    • , Lucila L. Elias
    • , Martin Metzger
    • , Edward O. List
    • , John J. Kopchick
    •  & Donato J. Jr
  • Article | | open

    Insulin-related gene (Insig) negatively regulates hepatic fatty acid synthesis, a process involved in development of non-alcoholic fatty liver disease (NAFLD). Here, the authors show that AMPK activation by metformin promotes Insig phosphorylation, stabilizing it and inhibiting lipogenic gene expression. This is protective against steatosis in diabetic mice.

    • Yamei Han
    • , Zhimin Hu
    • , Aoyuan Cui
    • , Zhengshuai Liu
    • , Fengguang Ma
    • , Yaqian Xue
    • , Yuxiao Liu
    • , Feifei Zhang
    • , Zehua Zhao
    • , Yanyan Yu
    • , Jing Gao
    • , Chun Wei
    • , Jingya Li
    • , Jing Fang
    • , Jia Li
    • , Jian-Gao Fan
    • , Bao-Liang Song
    •  & Yu Li
  • Article | | open

    Nuclear envelopathies are a group of diseases caused by genetic mutations in essential nuclear envelope genes. Here, the authors report a nuclear envelopathy with a homozygous nonsense variant in TOR1AIP1 which leads to changes in the nuclear morphology including large nuclear-spanning channels in patients’ fibroblasts.

    • Boris Fichtman
    • , Fadia Zagairy
    • , Nitzan Biran
    • , Yiftah Barsheshet
    • , Elena Chervinsky
    • , Ziva Ben Neriah
    • , Avraham Shaag
    • , Michael Assa
    • , Orly Elpeleg
    • , Amnon Harel
    •  & Ronen Spiegel
  • Article | | open

    The use of pluripotent-stem cell derived organs for transplantation would be promising, if organs can be grown in a suitable host. Here, the authors use interspecific blastocyst complementation to generate a mouse pluripotent stem cell-derived kidney in anephric Sall1 mutant rats.

    • Teppei Goto
    • , Hiromasa Hara
    • , Makoto Sanbo
    • , Hideki Masaki
    • , Hideyuki Sato
    • , Tomoyuki Yamaguchi
    • , Shinichi Hochi
    • , Toshihiro Kobayashi
    • , Hiromitsu Nakauchi
    •  & Masumi Hirabayashi
  • Article | | open

    Mammalian joints have poor regenerative capacity following amputation. Here, the authors show that in mice, stimulation of the amputation wound with BMP2 and BMP9 stimulates regeneration of a synovial joint that includes bone, cartilage and a synovial cavity.

    • Ling Yu
    • , Lindsay A. Dawson
    • , Mingquan Yan
    • , Katherine Zimmel
    • , Yu-Lieh Lin
    • , Connor P. Dolan
    • , Manjong Han
    •  & Ken Muneoka
  • Article | | open

    Heart grafts need good vascularization to survive. Here, the authors engineer perfusable constructs of human embryonic stem cell-derived endothelial cells seeded in collagen matrix in patterned microchannels that form anastomosed vessels in vitro and have increased coronary vascular perfusion on transplantation in rats.

    • Meredith A. Redd
    • , Nicole Zeinstra
    • , Wan Qin
    • , Wei Wei
    • , Amy Martinson
    • , Yuliang Wang
    • , Ruikang K. Wang
    • , Charles E. Murry
    •  & Ying Zheng
  • Article | | open

    The use of sodium-glucose transport protein 2 (SGLT2) inhibitors for the treatment of diabetes has been associated with euglycemic ketoacidosis and increased glucose production and glucagon secretion. Here Perry et al. show that these effects rely on both insulinopenia and dehydration, and thus suggest ways to manage the side effects associated with the use of SGLT2 inhibitors.

    • Rachel J. Perry
    • , Aviva Rabin-Court
    • , Joongyu D. Song
    • , Rebecca L. Cardone
    • , Yongliang Wang
    • , Richard G. Kibbey
    •  & Gerald I. Shulman
  • Article | | open

    Individuals show large variability in their capacity to lose weight and maintain this weight. Here, the authors perform GWAS in two weight loss intervention cohorts and identify two genetic loci associated with weight loss that are taken forward for Bayesian fine-mapping and functional assessment in flies.

    • Armand Valsesia
    • , Qiao-Ping Wang
    • , Nele Gheldof
    • , Jérôme Carayol
    • , Hélène Ruffieux
    • , Teleri Clark
    • , Victoria Shenton
    • , Lisa J. Oyston
    • , Gregory Lefebvre
    • , Sylviane Metairon
    • , Christian Chabert
    • , Ondine Walter
    • , Polina Mironova
    • , Paulina Lau
    • , Patrick Descombes
    • , Nathalie Viguerie
    • , Dominique Langin
    • , Mary-Ellen Harper
    • , Arne Astrup
    • , Wim H. Saris
    • , Robert Dent
    • , Greg G. Neely
    •  & Jörg Hager
  • Article | | open

    Metabolic pathways are increasingly recognized as crucial determinants of T cell function. Here the authors show that the balance between IFNγ and IL-10 production in human CD4 T cells is modulated by the cholesterol biosynthetic pathway.

    • Esperanza Perucha
    • , Rossella Melchiotti
    • , Jack A Bibby
    • , Wing Wu
    • , Klaus Stensgaard Frederiksen
    • , Ceri A. Roberts
    • , Zoe Hall
    • , Gaelle LeFriec
    • , Kevin A. Robertson
    • , Paul Lavender
    • , Jens Gammeltoft Gerwien
    • , Leonie S. Taams
    • , Julian L. Griffin
    • , Emanuele de Rinaldis
    • , Lisa G. M. van Baarsen
    • , Claudia Kemper
    • , Peter Ghazal
    •  & Andrew P. Cope
  • Article | | open

    The establishment of functional vasculatures requires the specification of newly formed vessels into veins and arteries. Here, Neal et al. use a combination of genetic approaches in mice and zebrafish to show that BMP signalling, via ALK3 and SMAD1/5, is required for venous specification during blood vessel development.

    • Alice Neal
    • , Svanhild Nornes
    • , Sophie Payne
    • , Marsha D. Wallace
    • , Martin Fritzsche
    • , Pakavarin Louphrasitthiphol
    • , Robert N. Wilkinson
    • , Kira M. Chouliaras
    • , Ke Liu
    • , Karen Plant
    • , Radhika Sholapurkar
    • , Indrika Ratnayaka
    • , Wiebke Herzog
    • , Gareth Bond
    • , Tim Chico
    • , George Bou-Gharios
    •  & Sarah De Val
  • Article | | open

    Obesity is associated with altered N-acylethanolamine levels (NAE). Here the authors show that deletion of the gene encoding N-acylphosphatidylethanolamine phospholipase D, a key enzyme for NAE synthesis, in intestinal cells of mice leads to the development of obesity and hepatic steatosis via a mechanism involving the gut-brain axis.

    • Amandine Everard
    • , Hubert Plovier
    • , Marialetizia Rastelli
    • , Matthias Van Hul
    • , Alice de Wouters d’Oplinter
    • , Lucie Geurts
    • , Céline Druart
    • , Sylvie Robine
    • , Nathalie M. Delzenne
    • , Giulio G. Muccioli
    • , Willem M. de Vos
    • , Serge Luquet
    • , Nicolas Flamand
    • , Vincenzo Di Marzo
    •  & Patrice D. Cani
  • Article | | open

    In atherosclerotic plaques, transformation of macrophages into foam cells is a key step in initiating the inflammatory response. Here Fan et al. show that casein kinase 2-interacting protein-1 (CKIP-1) limits foam cell formation and atherosclerosis by preventing expression of the scavenger receptor LOX-1 through REGγ-mediated degradation of Oct-1.

    • Jiao Fan
    • , Lifeng Liu
    • , Qingyan Liu
    • , Yu Cui
    • , Binwei Yao
    • , Minghua Zhang
    • , Yabing Gao
    • , Yesheng Fu
    • , Hongmiao Dai
    • , Jingkun Pan
    • , Ya Qiu
    • , Cui Hua Liu
    • , Fuchu He
    • , Yu Wang
    •  & Lingqiang Zhang
  • Article | | open

    Insulin resistance is associated with development of type 2 diabetes. Here the authors show that TAZ interacts with c-Jun and Tead4, inducing expression of the insulin receptor substrate 1 (IRS1) leading to increased glucose uptake in muscle, and that its activity is counteracted by statin administration.

    • Jun-Ha Hwang
    • , A Rum Kim
    • , Kyung Min Kim
    • , Jung Il Park
    • , Ho Taek Oh
    • , Sung A Moon
    • , Mi Ran Byun
    • , Hana Jeong
    • , Hyo Kyung Kim
    • , Michael B. Yaffe
    • , Eun Sook Hwang
    •  & Jeong-Ho Hong
  • Article | | open

    Selective autophagy receptors are thought to selectively recruit Atg8 positive membranes to cargo via their LIR motif. Here, the authors show the LIR motifs in OPTN and NDP52 are dispensable for selectivity, functioning instead to recruit additional receptors and amplify mitophagy.

    • Benjamin Scott Padman
    • , Thanh Ngoc Nguyen
    • , Louise Uoselis
    • , Marvin Skulsuppaisarn
    • , Lan K. Nguyen
    •  & Michael Lazarou
  • Article | | open

    GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

    • Tuomas O. Kilpeläinen
    • , Amy R. Bentley
    • , Raymond Noordam
    • , Yun Ju Sung
    • , Karen Schwander
    • , Thomas W. Winkler
    • , Hermina Jakupović
    • , Daniel I. Chasman
    • , Alisa Manning
    • , Ioanna Ntalla
    • , Hugues Aschard
    • , Michael R. Brown
    • , Lisa de las Fuentes
    • , Nora Franceschini
    • , Xiuqing Guo
    • , Dina Vojinovic
    • , Stella Aslibekyan
    • , Mary F. Feitosa
    • , Minjung Kho
    • , Solomon K. Musani
    • , Melissa Richard
    • , Heming Wang
    • , Zhe Wang
    • , Traci M. Bartz
    • , Lawrence F. Bielak
    • , Archie Campbell
    • , Rajkumar Dorajoo
    • , Virginia Fisher
    • , Fernando P. Hartwig
    • , Andrea R. V. R. Horimoto
    • , Changwei Li
    • , Kurt K. Lohman
    • , Jonathan Marten
    • , Xueling Sim
    • , Albert V. Smith
    • , Salman M. Tajuddin
    • , Maris Alver
    • , Marzyeh Amini
    • , Mathilde Boissel
    • , Jin Fang Chai
    • , Xu Chen
    • , Jasmin Divers
    • , Evangelos Evangelou
    • , Chuan Gao
    • , Mariaelisa Graff
    • , Sarah E. Harris
    • , Meian He
    • , Fang-Chi Hsu
    • , Anne U. Jackson
    • , Jing Hua Zhao
    • , Aldi T. Kraja
    • , Brigitte Kühnel
    • , Federica Laguzzi
    • , Leo-Pekka Lyytikäinen
    • , Ilja M. Nolte
    • , Rainer Rauramaa
    • , Muhammad Riaz
    • , Antonietta Robino
    • , Rico Rueedi
    • , Heather M. Stringham
    • , Fumihiko Takeuchi
    • , Peter J. van der Most
    • , Tibor V. Varga
    • , Niek Verweij
    • , Erin B. Ware
    • , Wanqing Wen
    • , Xiaoyin Li
    • , Lisa R. Yanek
    • , Najaf Amin
    • , Donna K. Arnett
    • , Eric Boerwinkle
    • , Marco Brumat
    • , Brian Cade
    • , Mickaël Canouil
    • , Yii-Der Ida Chen
    • , Maria Pina Concas
    • , John Connell
    • , Renée de Mutsert
    • , H. Janaka de Silva
    • , Paul S. de Vries
    • , Ayşe Demirkan
    • , Jingzhong Ding
    • , Charles B. Eaton
    • , Jessica D. Faul
    • , Yechiel Friedlander
    • , Kelley P. Gabriel
    • , Mohsen Ghanbari
    • , Franco Giulianini
    • , Chi Charles Gu
    • , Dongfeng Gu
    • , Tamara B. Harris
    • , Jiang He
    • , Sami Heikkinen
    • , Chew-Kiat Heng
    • , Steven C. Hunt
    • , M. Arfan Ikram
    • , Jost B. Jonas
    • , Woon-Puay Koh
    • , Pirjo Komulainen
    • , Jose E. Krieger
    • , Stephen B. Kritchevsky
    • , Zoltán Kutalik
    • , Johanna Kuusisto
    • , Carl D. Langefeld
    • , Claudia Langenberg
    • , Lenore J. Launer
    • , Karin Leander
    • , Rozenn N. Lemaitre
    • , Cora E. Lewis
    • , Jingjing Liang
    • , Behrooz Z. Alizadeh
    • , H. Marike Boezen
    • , Lude Franke
    • , Gerjan Navis
    • , Marianne Rots
    • , Morris Swertz
    • , Bruce H. R. Wolffenbuttel
    • , Cisca Wijmenga
    • , Jianjun Liu
    • , Reedik Mägi
    • , Ani Manichaikul
    • , Thomas Meitinger
    • , Andres Metspalu
    • , Yuri Milaneschi
    • , Karen L. Mohlke
    • , Thomas H. Mosley Jr.
    • , Alison D. Murray
    • , Mike A. Nalls
    • , Ei-Ei Khaing Nang
    • , Christopher P. Nelson
    • , Sotoodehnia Nona
    • , Jill M. Norris
    • , Chiamaka Vivian Nwuba
    • , Jeff O’Connell
    • , Nicholette D. Palmer
    • , George J. Papanicolau
    • , Raha Pazoki
    • , Nancy L. Pedersen
    • , Annette Peters
    • , Patricia A. Peyser
    • , Ozren Polasek
    • , David J. Porteous
    • , Alaitz Poveda
    • , Olli T. Raitakari
    • , Stephen S. Rich
    • , Neil Risch
    • , Jennifer G. Robinson
    • , Lynda M. Rose
    • , Igor Rudan
    • , Pamela J. Schreiner
    • , Robert A. Scott
    • , Stephen S. Sidney
    • , Mario Sims
    • , Jennifer A. Smith
    • , Harold Snieder
    • , Tamar Sofer
    • , John M. Starr
    • , Barbara Sternfeld
    • , Konstantin Strauch
    • , Hua Tang
    • , Kent D. Taylor
    • , Michael Y. Tsai
    • , Jaakko Tuomilehto
    • , André G. Uitterlinden
    • , M. Yldau van der Ende
    • , Diana van Heemst
    • , Trudy Voortman
    • , Melanie Waldenberger
    • , Patrik Wennberg
    • , Gregory Wilson
    • , Yong-Bing Xiang
    • , Jie Yao
    • , Caizheng Yu
    • , Jian-Min Yuan
    • , Wei Zhao
    • , Alan B. Zonderman
    • , Diane M. Becker
    • , Michael Boehnke
    • , Donald W. Bowden
    • , Ulf de Faire
    • , Ian J. Deary
    • , Paul Elliott
    • , Tõnu Esko
    • , Barry I. Freedman
    • , Philippe Froguel
    • , Paolo Gasparini
    • , Christian Gieger
    • , Norihiro Kato
    • , Markku Laakso
    • , Timo A. Lakka
    • , Terho Lehtimäki
    • , Patrik K. E. Magnusson
    • , Albertine J. Oldehinkel
    • , Brenda W. J. H. Penninx
    • , Nilesh J. Samani
    • , Xiao-Ou Shu
    • , Pim van der Harst
    • , Jana V. Van Vliet-Ostaptchouk
    • , Peter Vollenweider
    • , Lynne E. Wagenknecht
    • , Ya X. Wang
    • , Nicholas J. Wareham
    • , David R. Weir
    • , Tangchun Wu
    • , Wei Zheng
    • , Xiaofeng Zhu
    • , Michele K. Evans
    • , Paul W. Franks
    • , Vilmundur Gudnason
    • , Caroline Hayward
    • , Bernardo L. Horta
    • , Tanika N. Kelly
    • , Yongmei Liu
    • , Kari E. North
    • , Alexandre C. Pereira
    • , Paul M. Ridker
    • , E. Shyong Tai
    • , Rob M. van Dam
    • , Ervin R. Fox
    • , Sharon L. R. Kardia
    • , Ching-Ti Liu
    • , Dennis O. Mook-Kanamori
    • , Michael A. Province
    • , Susan Redline
    • , Cornelia M. van Duijn
    • , Jerome I. Rotter
    • , Charles B. Kooperberg
    • , W. James Gauderman
    • , Bruce M. Psaty
    • , Kenneth Rice
    • , Patricia B. Munroe
    • , Myriam Fornage
    • , L. Adrienne Cupples
    • , Charles N. Rotimi
    • , Alanna C. Morrison
    • , Dabeeru C. Rao
    •  & Ruth J. F. Loos
  • Article | | open

    Current treatments for age-related neovascular macular degeneration (nAMD) suffer from limited efficacy. Here, Zhao et al. show that pharmacological inhibition or genetic deletion of the mineralocorticoid receptor (MR) limits choroidal neovascularisation in rodents, and show in a pilot clinical study that targeting the MR pathway may provide clinical benefits in nAMD patiens.

    • Min Zhao
    • , Irmela Mantel
    • , Emmanuelle Gelize
    • , Xinxin Li
    • , Xiaoyue Xie
    • , Alejandro Arboleda
    • , Marie Seminel
    • , Rinath Levy-Boukris
    • , Marilyn Dernigoghossian
    • , Andrea Prunotto
    • , Charlotte Andrieu-Soler
    • , Carlo Rivolta
    • , Jérémie Canonica
    • , Marie-Christine Naud
    • , Sebastian Lechner
    • , Nicolette Farman
    • , Irene Bravo-Osuna
    • , Rocio Herrero-Vanrell
    • , Frederic Jaisser
    •  & Francine Behar-Cohen
  • Article | | open

    Obesity and the distribution of fat within the body are risk factors for cardiometabolic diseases. Here, Rask-Andersen et al. perform GWAS for bio-electrical impedance measurements in UK Biobank participants and identify 29 novel independent loci for fat distribution and a high degree of sex-heterogeneity.

    • Mathias Rask-Andersen
    • , Torgny Karlsson
    • , Weronica E. Ek
    •  & Åsa Johansson
  • Article | | open

    Beta II protein kinase C (βIIPKC) activation contributes to heart failure. Here the authors show, in a rat model of myocardial infarction, that heart failure outcome can be improved by selectively inhibiting the interaction between βIIPKC and its downstream mitochondrial target Mitofusin-1, and that this strategy is superior to global βIIPKC inhibition.

    • Julio C. B. Ferreira
    • , Juliane C. Campos
    • , Nir Qvit
    • , Xin Qi
    • , Luiz H. M. Bozi
    • , Luiz R. G. Bechara
    • , Vanessa M. Lima
    • , Bruno B. Queliconi
    • , Marie-Helene Disatnik
    • , Paulo M. M. Dourado
    • , Alicia J. Kowaltowski
    •  & Daria Mochly-Rosen
  • Article | | open

    Host metabolic reprogramming plays a role in functional responses against pathogens. Here, the authors characterise malonylated proteins in macrophages and show that malonylation of the glycolytic enzyme GAPDH impacts cytokine production by modulating both its enzymatic activity and RNA-binding capacity.

    • Silvia Galván-Peña
    • , Richard G. Carroll
    • , Carla Newman
    • , Elizabeth C. Hinchy
    • , Eva Palsson-McDermott
    • , Elektra K. Robinson
    • , Sergio Covarrubias
    • , Alan Nadin
    • , Andrew M. James
    • , Moritz Haneklaus
    • , Susan Carpenter
    • , Vincent P. Kelly
    • , Michael P. Murphy
    • , Louise K. Modis
    •  & Luke A. O’Neill
  • Article | | open

    Agouti-related peptide (AgRP) producing neurons regulate food intake and metabolic processes in peripheral organs. Here, the authors show that hypothalamic AgRP neurons alter whole body substrate utilization to favour carbohydrate usage and lipid storage.

    • João Paulo Cavalcanti-de-Albuquerque
    • , Jeremy Bober
    • , Marcelo R. Zimmer
    •  & Marcelo O. Dietrich
  • Article | | open

    Bone is innervated, and its turnover is affected by sympathetic nerve activity. Here, the authors show that prostaglandin E2, secreted by osteoblasts, activates the EP4 receptor on sensory nerves, inhibiting sympathetic nerve activity and modulating bone formation in mice.

    • Hao Chen
    • , Bo Hu
    • , Xiao Lv
    • , Shouan Zhu
    • , Gehua Zhen
    • , Mei Wan
    • , Amit Jain
    • , Bo Gao
    • , Yu Chai
    • , Mi Yang
    • , Xiao Wang
    • , Ruoxian Deng
    • , Lei Wang
    • , Yong Cao
    • , Shuangfei Ni
    • , Shen Liu
    • , Wen Yuan
    • , Huajiang Chen
    • , Xinzhong Dong
    • , Yun Guan
    • , Huilin Yang
    •  & Xu Cao
  • Article | | open

    Glutamine metabolism is increased in proliferating cells under hypoxia potentially generating exceeding nitrogen. Here the authors show that under hypoxia a specific metabolic pathway is activated to push glutamine carbons and excess nitrogen via the reductive pathway to dihyroorotate which is then secreted by the cells and that such pathway is necessary for tumor growth.

    • Yuanyuan Wang
    • , Changsen Bai
    • , Yuxia Ruan
    • , Miao Liu
    • , Qiaoyun Chu
    • , Li Qiu
    • , Chuanzhen Yang
    •  & Binghui Li
  • Article | | open

    Animal studies have shown that the nutritional status of parents can predispose the offspring to obesity and obesity-related diseases. Here the authors show that cardiac dysfunction induced by a high-fat diet persists for two generations in Drosophila, and that targeted expression of ATGL/bmm in the offspring, as well as inhibition of H3K27 trimethylation, is cardioprotective.

    • Maria Clara Guida
    • , Ryan Tyge Birse
    • , Alessandra Dall’Agnese
    • , Paula Coutinho Toto
    • , Soda Balla Diop
    • , Antonello Mai
    • , Peter D. Adams
    • , Pier Lorenzo Puri
    •  & Rolf Bodmer
  • Article | | open

    Imbalanced proteostasis is associated with diverse diseases, including ischemia/reperfusion injury in the heart. Here the authors show that the ATF6 arm of the unfolded protein response can be pharmacologically activated with a small molecule in vivo, providing protection from ischemia/reperfusion injury in the heart, the brain, and the kidney.

    • Erik A. Blackwood
    • , Khalid Azizi
    • , Donna J. Thuerauf
    • , Ryan J. Paxman
    • , Lars Plate
    • , Jeffery W. Kelly
    • , R. Luke Wiseman
    •  & Christopher C. Glembotski
  • Article | | open

    Impaired glucagon secretion in patients with diabetes causes hypoglycemia. Here the authors show that therapeutic concentrations of insulin inhibit alpha-cell glucagon secretion by stimulating delta-cell insulin receptor and the release of somatostatin. Blocking somatostatin secretion or action ameliorates this effect.

    • Elisa Vergari
    • , Jakob G. Knudsen
    • , Reshma Ramracheya
    • , Albert Salehi
    • , Quan Zhang
    • , Julie Adam
    • , Ingrid Wernstedt Asterholm
    • , Anna Benrick
    • , Linford J. B. Briant
    • , Margarita V. Chibalina
    • , Fiona M. Gribble
    • , Alexander Hamilton
    • , Benoit Hastoy
    • , Frank Reimann
    • , Nils J. G. Rorsman
    • , Ioannis I. Spiliotis
    • , Andrei Tarasov
    • , Yanling Wu
    • , Frances M. Ashcroft
    •  & Patrik Rorsman
  • Article | | open

    Estrogen promotes negative energy balance and preserves skeletal physiology. Here the authors show that loss of estrogen signalling after ablating estrogen receptor alpha (ERa) in specific hypothalamic neuronal populations leads to a marked sex-dependent increase in bone mass in female mice.

    • Candice B. Herber
    • , William C. Krause
    • , Liping Wang
    • , James R. Bayrer
    • , Alfred Li
    • , Matthew Schmitz
    • , Aaron Fields
    • , Breanna Ford
    • , Zhi Zhang
    • , Michelle S. Reid
    • , Daniel K. Nomura
    • , Robert A. Nissenson
    • , Stephanie M. Correa
    •  & Holly A. Ingraham
  • Article | | open

    Nephrogenesis ceases after postnatal day 2 in the mouse or after the 36th week of gestation in humans, but how this is regulated is unclear. Here, the authors identify a role for the RNA-binding protein Lin28 and suppression of let-7 microRNA in regulating the duration of nephrogenesis.

    • Alena V. Yermalovich
    • , Jihan K. Osborne
    • , Patricia Sousa
    • , Areum Han
    • , Melissa A. Kinney
    • , Michael J. Chen
    • , Daisy A. Robinton
    • , Helen Montie
    • , Dan S. Pearson
    • , Sean B. Wilson
    • , Alexander N. Combes
    • , Melissa H. Little
    •  & George Q. Daley
  • Article | | open

    The Ca2+-activated Cl- channel TMEM16A/Anoctamin 1 (ANO1) mediates secretion and intestinal motility in gastrointestinal epithelia and smooth muscle cells. Here, the authors show a role for ANO1 in zebrafish skeletal muscle which is activated by SR Ca2+ release during excitation-contraction coupling.

    • Anamika Dayal
    • , Shu Fun J. Ng
    •  & Manfred Grabner
  • Article | | open

    AMPK is regulates cellular energy and has been extensively studied, although our knowledge of downstream substrates is incomplete. Here, Chen et al. perform global quantitative analysis for AMPK-dependent sites and validate one hit, ARMC10, as a direct AMPK effector of mitochondrial dynamics.

    • Zhen Chen
    • , Caoqi Lei
    • , Chao Wang
    • , Nan Li
    • , Mrinal Srivastava
    • , Mengfan Tang
    • , Huimin Zhang
    • , Jong Min Choi
    • , Sung Yun Jung
    • , Jun Qin
    •  & Junjie Chen
  • Article | | open

    Thrombospondin 4 has been shown to protect the heart and the skeletal muscle by enhancing matrix secretion and membrane stability thanks to its intracellular function. Here the authors show that thrombospondin 3 exacerbates injury-induced cardiomyopathy and promotes destabilization of the cardiomyocyte membrane by impairing integrin trafficking to the sarcolemma.

    • Tobias G. Schips
    • , Davy Vanhoutte
    • , Alexander Vo
    • , Robert N. Correll
    • , Matthew J. Brody
    • , Hadi Khalil
    • , Jason Karch
    • , Andoria Tjondrokoesoemo
    • , Michelle A. Sargent
    • , Marjorie Maillet
    • , Robert S. Ross
    •  & Jeffery D. Molkentin
  • Article | | open

    TOP1MT is a topoisomerase that is localised to mitochondria. Here, the authors show that TOP1MT has a tumor promoting role in hepatocellular carcinoma by supporting mitochondrial translation and that its deficiency limits tumorigenicity.

    • S. A. Baechler
    • , V. M. Factor
    • , I. Dalla Rosa
    • , A. Ravji
    • , D. Becker
    • , S. Khiati
    • , L. M. Miller Jenkins
    • , M. Lang
    • , C. Sourbier
    • , S. A. Michaels
    • , L. M. Neckers
    • , H. L. Zhang
    • , A. Spinazzola
    • , S. N. Huang
    • , J. U. Marquardt
    •  & Y. Pommier
  • Article | | open

    While human lifespan is only moderately heritable, “getting old” runs in families. Here, van den Berg et al. study mortality data from three-generation cohorts to define a threshold for longevity and find that individuals have an increasing survival advantage with each additional relative in the top 10% survivors of their birth cohort.

    • Niels van den Berg
    • , Mar Rodríguez-Girondo
    • , Ingrid K. van Dijk
    • , Rick J. Mourits
    • , Kees Mandemakers
    • , Angelique A. P. O. Janssens
    • , Marian Beekman
    • , Ken R. Smith
    •  & P. Eline Slagboom
  • Article | | open

    Estimated glomerular filtration rate (eGFR) is a measure of kidney function used to define chronic kidney disease. Here, Morris et al. perform trans-ethnic genome-wide meta-analyses for eGFR in 312,468 individuals and identify novel loci and downstream putative causal genes.

    • Andrew P. Morris
    • , Thu H. Le
    • , Haojia Wu
    • , Artur Akbarov
    • , Peter J. van der Most
    • , Gibran Hemani
    • , George Davey Smith
    • , Anubha Mahajan
    • , Kyle J. Gaulton
    • , Girish N. Nadkarni
    • , Adan Valladares-Salgado
    • , Niels Wacher-Rodarte
    • , Josyf C. Mychaleckyj
    • , Nicole D. Dueker
    • , Xiuqing Guo
    • , Yang Hai
    • , Jeffrey Haessler
    • , Yoichiro Kamatani
    • , Adrienne M. Stilp
    • , Gu Zhu
    • , James P. Cook
    • , Johan Ärnlöv
    • , Susan H. Blanton
    • , Martin H. de Borst
    • , Erwin P. Bottinger
    • , Thomas A. Buchanan
    • , Sylvia Cechova
    • , Fadi J. Charchar
    • , Pei-Lun Chu
    • , Jeffrey Damman
    • , James Eales
    • , Ali G. Gharavi
    • , Vilmantas Giedraitis
    • , Andrew C. Heath
    • , Eli Ipp
    • , Krzysztof Kiryluk
    • , Holly J. Kramer
    • , Michiaki Kubo
    • , Anders Larsson
    • , Cecilia M. Lindgren
    • , Yingchang Lu
    • , Pamela A. F. Madden
    • , Grant W. Montgomery
    • , George J. Papanicolaou
    • , Leslie J. Raffel
    • , Ralph L. Sacco
    • , Elena Sanchez
    • , Holger Stark
    • , Johan Sundstrom
    • , Kent D. Taylor
    • , Anny H. Xiang
    • , Aleksandra Zivkovic
    • , Lars Lind
    • , Erik Ingelsson
    • , Nicholas G. Martin
    • , John B. Whitfield
    • , Jianwen Cai
    • , Cathy C. Laurie
    • , Yukinori Okada
    • , Koichi Matsuda
    • , Charles Kooperberg
    • , Yii-Der Ida Chen
    • , Tatjana Rundek
    • , Stephen S. Rich
    • , Ruth J. F. Loos
    • , Esteban J. Parra
    • , Miguel Cruz
    • , Jerome I. Rotter
    • , Harold Snieder
    • , Maciej Tomaszewski
    • , Benjamin D. Humphreys
    •  & Nora Franceschini
  • Article | | open

    Serine synthesis from glucose is required even when serine is available from the environment. Here, the authors explain this paradox by showing that the enzyme PHGDH enables nucleotide synthesis by coordinating anabolic fluxes related to central carbon metabolism, independent of its role in serine production.

    • Michael A. Reid
    • , Annamarie E. Allen
    • , Shiyu Liu
    • , Maria V. Liberti
    • , Pei Liu
    • , Xiaojing Liu
    • , Ziwei Dai
    • , Xia Gao
    • , Qian Wang
    • , Ying Liu
    • , Luhua Lai
    •  & Jason W. Locasale
  • Article | | open

    Gelsolin is an actin severing and capping protein that regulates cytoskeletal remodeling. Here the authors show that gelsolin is negatively regulated in the heart by PI3Kα‐ generated PIP3, and that loss of gelsolin activity prevents adverse cytoskeletal remodeling and heart failure.

    • Vaibhav B. Patel
    • , Pavel Zhabyeyev
    • , Xueyi Chen
    • , Faqi Wang
    • , Manish Paul
    • , Dong Fan
    • , Brent A. McLean
    • , Ratnadeep Basu
    • , Pu Zhang
    • , Saumya Shah
    • , John F. Dawson
    • , W. Glen Pyle
    • , Mousumi Hazra
    • , Zamaneh Kassiri
    • , Saugata Hazra
    • , Bart Vanhaesebroeck
    • , Christopher A. McCulloch
    •  & Gavin Y. Oudit
  • Article | | open

    Developing new technologies for the neuromodulation of the vagus nerve can enable therapeutic strategies for body weight control in obese patients. Here, the authors present a battery-free self-powered implantable vagus nerve stimulation system that electrically responds to stomach movement.

    • Guang Yao
    • , Lei Kang
    • , Jun Li
    • , Yin Long
    • , Hao Wei
    • , Carolina A. Ferreira
    • , Justin J. Jeffery
    • , Yuan Lin
    • , Weibo Cai
    •  & Xudong Wang
  • Article | | open

    The mechanisms underlying the regenerative capacity of the liver are not fully understood. Here, the authors show that the acute regenerative response to liver injury in mice is regulated by the communication involving the vagus nerve, macrophages, and hepatocytes, leading to hepatic FoxM1 activation and promotion of overall survival.

    • Tomohito Izumi
    • , Junta Imai
    • , Junpei Yamamoto
    • , Yohei Kawana
    • , Akira Endo
    • , Hiroto Sugawara
    • , Masato Kohata
    • , Yoichiro Asai
    • , Kei Takahashi
    • , Shinjiro Kodama
    • , Keizo Kaneko
    • , Junhong Gao
    • , Kenji Uno
    • , Shojiro Sawada
    • , Vladimir V. Kalinichenko
    • , Yasushi Ishigaki
    • , Tetsuya Yamada
    •  & Hideki Katagiri
  • Article | | open

    Tropinone is an intermediate in the biosynthesis of tropane alkaloids. Here, the authors discovered the enzymes AbPYKS and AbCYP82M3, a non-canonical polyketide synthase and a cytochrome P450, that work sequentially to form tropinone from N-methyl-Δ1-pyrrolinium cation.

    • Matthew A. Bedewitz
    • , A. Daniel Jones
    • , John C. D’Auria
    •  & Cornelius S. Barry
  • Article | | open

    Understanding the pH changes at cell surfaces is important for understanding the mechanisms of different physiological processes. Here, the authors report on the development of a cell membrane anchored gold nanoparticle for surface enhanced Raman spectroscopy determination of pH.

    • Leonardo Puppulin
    • , Shigekuni Hosogi
    • , Hongxin Sun
    • , Kazuhiko Matsuo
    • , Toshio Inui
    • , Yasuaki Kumamoto
    • , Toshinobu Suzaki
    • , Hideo Tanaka
    •  & Yoshinori Marunaka
  • Article | | open

    The molecular pathway(s) driving antipsychotics (AP) induced hyperphagia remains unclear. A novel C. elegans system is used here to screen for FDA approved drugs that selectively suppresses this response, unraveling potential molecular mediators influencing AP induced hyperphagia in mouse models.

    • Anabel Perez-Gomez
    • , Maria Carretero
    • , Natalie Weber
    • , Veronika Peterka
    • , Alan To
    • , Viktoriya Titova
    • , Gregory Solis
    • , Olivia Osborn
    •  & Michael Petrascheck
  • Article | | open

    Studying the genetic underpinnings of physical activity and sleep duration can be confounded by self-reporting. Here, Doherty et al. use data from 91,105 UK Biobank participants, whose activity had been monitored for a week by a wearable device, for genome-wide association analysis and identify 14 loci.

    • Aiden Doherty
    • , Karl Smith-Byrne
    • , Teresa Ferreira
    • , Michael V. Holmes
    • , Chris Holmes
    • , Sara L. Pulit
    •  & Cecilia M. Lindgren
  • Article | | open

    Histone lysine demethylases (KDMs) can mediate transcriptional reprogramming in disease states. Here the authors show that KDM3A promotes left ventricular hypertrophy and cardiac fibrosis by activating the transcription of Timp1, and that pharmacological inhibition of KDM3A attenuates cardiac remodeling induced by pressure overload.

    • Qing-Jun Zhang
    • , Tram Anh T. Tran
    • , Ming Wang
    • , Mark J. Ranek
    • , Kristen M. Kokkonen-Simon
    • , Jason Gao
    • , Xiang Luo
    • , Wei Tan
    • , Viktoriia Kyrychenko
    • , Lan Liao
    • , Jianming Xu
    • , Joseph A. Hill
    • , Eric N. Olson
    • , David A. Kass
    • , Elisabeth D. Martinez
    •  & Zhi-Ping Liu
  • Article | | open

    Drp1 and Dnm2 have been implicated in mitochondrial fission events, although their specific activities in constriction and scission have been unclear. Here, the authors demonstrate that Drp1 is sufficient to constrict and sever mitochondrial and peroxisomal membranes in the absence of Dnm proteins.

    • Sukrut C. Kamerkar
    • , Felix Kraus
    • , Alice J. Sharpe
    • , Thomas J. Pucadyil
    •  & Michael T. Ryan
  • Article | | open

    Cubilin and the transmembrane protein amnionless (AMN) form the endocytic receptor cubam that is essential for intestinal vitamin B12 uptake. Here the authors present the 2.3 Å crystal structure of AMN in complex with the amino-terminal region of cubilin and discuss cubam architecture and disease causing mutations.

    • Casper Larsen
    • , Anders Etzerodt
    • , Mette Madsen
    • , Karsten Skjødt
    • , Søren Kragh Moestrup
    •  & Christian Brix Folsted Andersen
  • Article | | open

    The tuberculosis pandemic requires new methods for diagnosing and containing infections prior to active disease. Here, the authors performed a multi-site observational study within sub-Saharan Africa and present serum and plasma metabolic signatures that can predict the onset of active TB with a high degree of sensitivity and specificity.

    • January Weiner 3rd
    • , Jeroen Maertzdorf
    • , Jayne S. Sutherland
    • , Fergal J. Duffy
    • , Ethan Thompson
    • , Sara Suliman
    • , Gayle McEwen
    • , Bonnie Thiel
    • , Shreemanta K. Parida
    • , Joanna Zyla
    • , Willem A. Hanekom
    • , Robert P. Mohney
    • , W. Henry Boom
    • , Harriet Mayanja-Kizza
    • , Rawleigh Howe
    • , Hazel M. Dockrell
    • , Tom H. M. Ottenhoff
    • , Thomas J. Scriba
    • , Daniel E. Zak
    • , Gerhard Walzl
    • , Stefan H. E. Kaufmann
    • , Almaz Abebe
    • , Brian Abel
    • , Richard Adegbola
    • , Ifedayo Adetifa
    • , Lyn Ambrose
    • , Peter Andersen
    • , Martin Antonio
    • , Abraham Aseffa
    • , Debbie van Baarle
    • , Lew Barker
    • , Yonas Bekele
    • , Nicole Bilek
    • , Gillian F. Black
    • , Mark Bowmaker
    • , Keith Branson
    • , Michael Brennan
    • , Novel N. Chegou
    • , Femia Chilongo
    • , William Kwong Chung
    • , Tumani Corrah
    • , Ameilia C. Crampin
    • , Mark Doherty
    • , Gregory Dolganov
    • , Simon Donkor
    • , Katrina Downing
    • , Michelle Fisher
    • , Kees L. M. C. Franken
    • , Neil French
    • , Larry Geiter
    • , Annemieke Geluk
    • , Robert Golinski
    • , Patricia Gorak-Stolinska
    • , Marielle C. Haks
    • , Philip Hill
    • , Jane Hughes
    • , Yun-Gyoung Hur
    • , Rachel Iwnetu
    • , Marc Jacobson
    • , Moses Joloba
    • , Simone A. Joosten
    • , Benjamin Kagina
    • , Desta Kassa
    • , Hussein Kisingo
    • , Michel R. Klein
    • , Magdalena Kriel
    • , Maeve Lalor
    • , Ji-Sook Lee
    • , Andre G. Loxton
    • , Hassan Mahomed
    • , Krista E. van Meijgaarden
    • , Tsehayenesh Mesele
    • , Frank Miedema
    • , Adane Mihret
    • , Humphrey Mulenga
    • , Stefanie Muller
    • , Hazzie Mvula
    • , Nonhlanhla Nene
    • , Bagrey Ngwira
    • , Mary Nsereko
    • , Brenda Okwera
    • , Martin Ota
    • , Adam Penn-Nicholson
    • , Nelita Du Plessis
    • , S. Ramachandran
    • , Ida Rosenkrands
    • , Jerry Sadoff
    • , Jacky Saul
    • , Gary Schoolnik
    • , Felanji Simukonda
    • , Donata Sizemore
    • , Steven Smith
    • , Anne Ben Smith
    • , Gian van der Spuy
    • , Kim Stanley
    • , David Tabb
    • , Mesfin Tafesse
    • , Belete Tegbaru
    • , Toyin Togun
    • , Gerhardus Tromp
    • , Tran Van
    • , Kate Watkins
    • , Frank Weichold
    • , Karin Weldingh
    • , Lawrence Yamuah
    •  & Sarah Zalwango
  • Article | | open

    Obesity increases the risk of hepatocellular carcinoma (HCC) especially in men. Here the authors find a potential mechanistic explanation by showing that, in mice, obesity-induced STAT3 cooperates with the androgen receptor to activate the mTORC pathway through up regulation of CCRK, resulting in hepatic steatosis worsening and HCC development via metabolic and immune reprogramming.

    • Hanyong Sun
    • , Weiqin Yang
    • , Yuan Tian
    • , Xuezhen Zeng
    • , Jingying Zhou
    • , Myth T. S. Mok
    • , Wenshu Tang
    • , Yu Feng
    • , Liangliang Xu
    • , Anthony W. H. Chan
    • , Joanna H. Tong
    • , Yue-Sun Cheung
    • , Paul B. S. Lai
    • , Hector K. S. Wang
    • , Shun-Wa Tsang
    • , King-Lau Chow
    • , Mengying Hu
    • , Rihe Liu
    • , Leaf Huang
    • , Bing Yang
    • , Pengyuan Yang
    • , Ka-Fai To
    • , Joseph J. Y. Sung
    • , Grace L. H. Wong
    • , Vincent W. S. Wong
    •  & Alfred S. L. Cheng