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  1. Genetic code expansion, click chemistry, and light-activated PI3K reveal details of membrane protein trafficking downstream of receptor tyrosine kinases

    This article has 12 authors:
    1. Duk-Su Koh
    2. Anastasiia Stratiievska
    3. Subhashis Jana
    4. Shauna C. Otto
    5. Teresa M. Swanson
    6. Anthony Nhim
    7. Sara Carlson
    8. Marium Raza
    9. Lígia Araujo Naves
    10. Eric N. Senning
    11. Ryan Mehl
    12. Sharona E. Gordon
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study develops a new and important method for dissecting out two overlapping cell signaling pathways, phosphoinositide signaling and membrane protein trafficking. The combination of two state-of-the-art spectroscopic techniques provides compelling evidence for a reciprocal influence between an enzyme and a channel. The work will be of interest to the broader cell biology, biophysics and biochemistry communities.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity
  2. Intermittent fasting promotes type 3 innate lymphoid cells secreting IL-22 contributing to the beigeing of white adipose tissue

    This article has 10 authors:
    1. Hong Chen
    2. Lijun Sun
    3. Lu Feng
    4. Xue Han
    5. Yunhua Zhang
    6. Wenbo Zhai
    7. Zehe Zhang
    8. Michael Mulholland
    9. Weizhen Zhang
    10. Yue Yin
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study provides valuable findings showing the production of IL-22 from intestinal ILC3 during intermittent fasting promotes beigeing of white adipose tissue. The authors provided solid data and mechanistic insight by which IL-22-derived from ILC3 directly induces beigeing.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity
  3. CRISPR-Cas9 knockdown of ESR1 in preoptic GABA-kisspeptin neurons suppresses the preovulatory surge and estrous cycles in female mice

    This article has 6 authors:
    1. Jenny Clarkson
    2. Siew Hoong Yip
    3. Robert Porteous
    4. Alexia Kauff
    5. Alison K Heather
    6. Allan E Herbison
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important study provides convincing evidence of the criticality of estradiol – estrogen receptor-mediated upregulation of kisspeptin within neurons of the preoptic area to generate an ovulation-inducing luteinizing hormone surge. The use of in vivo CRIPSR-Cas9 is novel in this system and provides a road map for future studies in reproductive neuroendocrinology. This paper will be of interest to reproductive neuroscientists and endocrinologists.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity
  4. Tmem263 deletion disrupts the GH/IGF-1 axis and causes dwarfism and impairs skeletal acquisition

    This article has 5 authors:
    1. Dylan C Sarver
    2. Jean Garcia-Diaz
    3. Muzna Saqib
    4. Ryan C Riddle
    5. G William Wong
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study discloses important physiological function for TMEM63 in regulating postnatal growth in mice. The data supporting the impaired body growth and skeletal phenotype as well as disrupted growth hormone/insulin-like growth factor-I (GH/IGF-I) signaling in TMEM63 knockout mice are compelling. However, to establish that alteration of hepatic GH/IGF-I signaling is the cause for observed growth and skeletal phenotype in TMEM63 knockout mice would need additional work.

    Reviewed by eLife

    This article has 8 evaluationsAppears in 2 listsLatest version Latest activity
  5. Inhibition of CERS1 in skeletal muscle exacerbates age-related muscle dysfunction

    This article has 17 authors:
    1. Martin Wohlwend
    2. Pirkka-Pekka Laurila
    3. Ludger JE Goeminne
    4. Tanes Lima
    5. Ioanna Daskalaki
    6. Xiaoxu Li
    7. Giacomo von Alvensleben
    8. Barbara Crisol
    9. Renata Mangione
    10. Hector Gallart-Ayala
    11. Amélia Lalou
    12. Olivier Burri
    13. Stephen Butler
    14. Jonathan Morris
    15. Nigel Turner
    16. Julijana Ivanisevic
    17. Johan Auwerx
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This solid study presents valuable insights into the role of Cers1 on skeletal muscle function during aging, although further substantiation would help to fully establish the experimental assertions. It examines an unexplored aspect of muscle biology that is a relevant opening to future studies in this area of research.

    Reviewed by eLife

    This article has 7 evaluationsAppears in 2 listsLatest version Latest activity
  6. The MODY-associated KCNK16 L114P mutation increases islet glucagon secretion and limits insulin secretion resulting in transient neonatal diabetes and glucose dyshomeostasis in adults

    This article has 11 authors:
    1. Arya Y Nakhe
    2. Prasanna K Dadi
    3. Jinsun Kim
    4. Matthew T Dickerson
    5. Soma Behera
    6. Jordyn R Dobson
    7. Shristi Shrestha
    8. Jean-Philippe Cartailler
    9. Leesa Sampson
    10. Mark A Magnuson
    11. David A Jacobson
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study characterizes how a point mutation in the TALK-1 potassium channel, encoded by the KCNK16 gene, causes MODY diabetes. The mutation, L114P, causes a gain-of-function to increase K+ currents and inhibit glucose-stimulated insulin secretion. Increased glucagon likely results from paracrine effects in the islets. The data are convincing and the work will be valuable for understanding islet function.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity
  7. Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model

    This article has 3 authors:
    1. Yunlu Xue
    2. Yimin Zhou
    3. Constance L Cepko
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This fundamental study advances our understanding of the cell specific treatment of cone photoreceptor degeneration by Txnip. The evidence supporting the conclusions is compelling with rigorous genetic manipulation of Txnip mutations. The work will be of broad interest to vision researchers, cell biologists and biochemists.

    Reviewed by eLife

    This article has 13 evaluationsAppears in 2 listsLatest version Latest activity
  8. A computational model predicts sex-specific responses to calcium channel blockers in mammalian mesenteric vascular smooth muscle

    This article has 9 authors:
    1. Gonzalo Hernandez-Hernandez
    2. Samantha C O'Dwyer
    3. Pei-Chi Yang
    4. Collin Matsumoto
    5. Mindy Tieu
    6. Zhihui Fong
    7. Timothy J Lewis
    8. L Fernando Santana
    9. Colleen E Clancy
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The study is of importance for the cardiac modeling field by developing a novel mathematical model with sex difference. The data are compelling, and the model is helpful for mechanistic understanding, and thus is also important for experimental physiology. The model is based on experimental data and validated against some experimental data.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity
  9. Septin 7 interacts with Numb to preserve sarcomere structural organization and muscle contractile function

    This article has 12 authors:
    1. Rita De Gasperi
    2. Laszlo Csernoch
    3. Beatrix Dienes
    4. Monika Gonczi
    5. Jayanta K Chakrabarty
    6. Shahar Goeta
    7. Abdurrahman Aslan
    8. Carlos A Toro
    9. David Karasik
    10. Lewis M Brown
    11. Marco Brotto
    12. Christopher P Cardozo
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This convincing study demonstrates a potentially important role for the factor Numb in skeletal muscle excitation-contraction coupling, since a Numb knockout reduced contractile force. The authors thus demonstrate a novel role for Numb in calcium release in skeletal muscle.

    Reviewed by eLife

    This article has 15 evaluationsAppears in 2 listsLatest version Latest activity
  10. Calcineurin inhibition enhances Caenorhabditis elegans lifespan by defecation defects-mediated calorie restriction and nuclear hormone signaling

    This article has 3 authors:
    1. Priyanka Das
    2. Alejandro Aballay
    3. Jogender Singh
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This useful study has the potential to reveal insights into how calcineurin influences C. elegans lifespan through its role in controlling the defecation motor program. Currently, the evidence in support of the conclusions is still incomplete, largely due to concerns about partial gene inactivation by RNAi. The inclusion of experiments using a tax-6 null allele would mitigate these concerns.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  11. Calcineurin inhibition enhances Caenorhabditis elegans lifespan by defecation defects-mediated calorie restriction and nuclear hormone signaling

    This article has 3 authors:
    1. Priyanka Das
    2. Alejandro Aballay
    3. Jogender Singh
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This useful study has the potential to reveal insights into how calcineurin influences C. elegans lifespan through its role in controlling the defecation motor program. Currently, the evidence in support of the conclusions is still incomplete, largely due to concerns about partial gene inactivation by RNAi. The inclusion of experiments using a tax-6 null allele would mitigate these concerns.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  12. Divergent regulation of KCNQ1/E1 by targeted recruitment of protein kinase A to distinct sites on the channel complex

    This article has 6 authors:
    1. Xinle Zou
    2. Sri Karthika Shanmugam
    3. Scott A Kanner
    4. Kevin J Sampson
    5. Robert S Kass
    6. Henry M Colecraft
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important study provides a substantial advance with a method by which a protein target resistant to therapeutic approaches can be uniquely modulated by a cellular protein kinase ferried by nanobodies to a precise molecular site of recruitment. Evidence for this major claim is compelling, but evidence for some of the minor claims seems incomplete. The work will be of broad interest to cell biologists, cardiovascular researchers, and drug developers.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  13. Leveraging inter-individual transcriptional correlation structure to infer discrete signaling mechanisms across metabolic tissues

    This article has 26 authors:
    1. Mingqi Zhou
    2. Ian Tamburini
    3. Cassandra Van
    4. Jeffrey Molendijk
    5. Christy M Nguyen
    6. Ivan Yao-Yi Chang
    7. Casey Johnson
    8. Leandro M Velez
    9. Youngseo Cheon
    10. Reichelle Yeo
    11. Hosung Bae
    12. Johnny Le
    13. Natalie Larson
    14. Ron Pulido
    15. Carlos HV Nascimento-Filho
    16. Cholsoon Jang
    17. Ivan Marazzi
    18. Jamie Justice
    19. Nicholas Pannunzio
    20. Andrea L Hevener
    21. Lauren Sparks
    22. Erin E Kershaw
    23. Dequina Nicholas
    24. Benjamin L Parker
    25. Selma Masri
    26. Marcus M Seldin
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important paper provides web based interface for cross-tissue analysis of omics datasets from – so far – two different human populations, with compelling evidence that the tool can be used to make meaningful scientific discoveries. Conceptually, these analyses are relevant for any systems biologist or bioinformatician who is interested in integrating large population datasets. Currently, the resource is already of use for scientists studying the HMDP or using GTEx data, and we hope to see updates in the coming years that incorporate more populations and more datatypes, which could make it a general tool for a wide community.

    Reviewed by eLife

    This article has 8 evaluationsAppears in 2 listsLatest version Latest activity
  14. Ryanodine receptor 2 inhibition reduces dispersion of cardiac repolarization, improves contractile function, and prevents sudden arrhythmic death in failing hearts

    This article has 5 authors:
    1. Pooja Joshi
    2. Shanea Estes
    3. Deeptankar DeMazumder
    4. Bjorn C Knollmann
    5. Swati Dey
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important study examined the use of dantrolene, a Ryanodine Receptor stabilizer, in slowing pathological progression of pressure-overload heart failure in a guinea pig model and reducing arrhythmias. Convincing data were collected and analyzed using validated methodology and can be used as a starting point for future studies of dantrolene in Ca2+ handling in ROS production and further deterioration of cardiac function in chronic heart failure.

    Reviewed by eLife

    This article has 7 evaluationsAppears in 2 listsLatest version Latest activity
  15. Molecular tuning of sea anemone stinging

    This article has 8 authors:
    1. Lily S He
    2. Yujia Qi
    3. Corey AH Allard
    4. Wendy A Valencia-Montoya
    5. Stephanie P Krueger
    6. Keiko Weir
    7. Agnese Seminara
    8. Nicholas W Bellono
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This is an important paper that links distinctive stinging behavior of two related anemones occupying different ecological niches to varying inactivation properties of voltage-gated calcium channels conferred by auxiliary Cavβ subunits. Further convincing evidence is provided that these differences are mediated by alternative splicing of Cavβ subunit of the calcium channel. The study will be of interest to scientists studying Ca2+ signaling, ion channel biophysicists, and marine biologists.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity
  16. Melanocortin 1 receptor regulates cholesterol and bile acid metabolism in the liver

    This article has 8 authors:
    1. Keshav Thapa
    2. James J Kadiri
    3. Karla Saukkonen
    4. Iida Pennanen
    5. Bishwa Ghimire
    6. Minying Cai
    7. Eriika Savontaus
    8. Petteri Rinne
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The significance of this manuscript is that is provides useful information for the field of hepatology and endocrinology on the regulatory mechanisms of cholesterol homeostasis by melanocortin. The authors provide solid evidence utilizing both in vivo and in vitro molecular, cellular, and biochemical approaches to support their claims.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  17. Mechanistic insights into robust cardiac IKs potassium channel activation by aromatic polyunsaturated fatty acid analogues

    This article has 8 authors:
    1. Briana M Bohannon
    2. Jessica J Jowais
    3. Leif Nyberg
    4. Vanessa Olivier-Meo
    5. Valentina Corradi
    6. D Peter Tieleman
    7. Sara I Liin
    8. H Peter Larsson
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This work reports important findings regarding the regulation of ion channels by polyunsaturated fatty acids (PUFAs) through the identification of novel aromatic PUFA analogs with potent effects on the IKs channels, which allow for mechanistic insights into their mode of action. The experiments are solid, combining site-directed mutagenesis, electrophysiological and pharmacological approaches to dissect the different molecular mechanisms and sites involved in the functional interactions. This work will be of broad interest to ion channel biophysicists, physiologists, and medical chemists interested in drug development for LQT syndrome. The study presents some limitations that may need to be addressed or further discussed, in order to strengthen the conclusions reached in the study.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  18. An acute microglial metabolic response controls metabolism and improves memory

    This article has 20 authors:
    1. Anne Drougard
    2. Eric H Ma
    3. Vanessa Wegert
    4. Ryan Sheldon
    5. Ilaria Panzeri
    6. Naman Vatsa
    7. Stefanos Apostle
    8. Luca Fagnocchi
    9. Judith Schaf
    10. Klaus Gossens
    11. Josephine Völker
    12. Shengru Pang
    13. Anna Bremser
    14. Erez Dror
    15. Francesca Giacona
    16. Sagar Sagar
    17. Michae X Henderson
    18. Marco Prinz
    19. Russell G Jones
    20. John Andrew Pospisilik
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important study demonstrates a link between an acute high fat diet, microglial metabolism and improved higher cognitive function. The evidence supporting the proposed model is incomplete at this stage and would benefit from additional experiments probing the link between microglial metabolism and higher cognitive function. Following more mechanistic dissection, this work will be of interest to a broad audience in the field of neuroscience, metabolism, and immunology.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity
  19. High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen

    This article has 9 authors:
    1. Wan-ping Yang
    2. Mei-qi Li
    3. Jie Ding
    4. Jia-yan Li
    5. Gang Wu
    6. Bao Liu
    7. Yu-qi Gao
    8. Guo-hua Wang
    9. Qian-qian Luo
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This useful study reports that a week or more of hypoxia exposure in mice increases erythropoiesis and decreases the number of iron-recycling macrophages in the spleen, compromising their capacity for red blood cell phagocytosis – reflected by increased mature erythrocyte retention in the spleen. Compared to an earlier version, the study has been strengthened with mouse experiments under hypobaric hypoxia and complemented by extensive ex vivo analyses. Unfortunately, while some of the evidence is solid, the work as it currently stands only incompletely supports the authors' hypotheses. While the study would benefit from additional experiments that more directly buttress the central claims, it should be of interest to the fields of hemopoiesis and bone marrow biology and possibly also blood cancer.

    Reviewed by eLife

    This article has 14 evaluationsAppears in 2 listsLatest version Latest activity
  20. Calcium and bicarbonate signaling pathways have pivotal, resonating roles in matching ATP production to demand

    This article has 8 authors:
    1. Maura Greiser
    2. Mariusz Karbowski
    3. Aaron David Kaplan
    4. Andrew Kyle Coleman
    5. Nicolas Verhoeven
    6. Carmen A Mannella
    7. W Jonathan Lederer
    8. Liron Boyman
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The important work presented here provides findings that substantially advance our understanding of a major research question into how bicarbonate/CO2 signaling regulates cardiac mitochondrial energy supply. The methods, data, and analyses broadly support the claims with only minor weaknesses concerning the exact spatial location of the enzymes involved. The work will be of broad interest to cell biologists and biochemists interested in metabolic control.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity