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  1. Mobile barrier mechanisms for Na+-coupled symport in an MFS sugar transporter

    This article has 14 authors:
    1. Parameswaran Hariharan
    2. Yuqi Shi
    3. Satoshi Katsube
    4. Katleen Willibal
    5. Nathan D Burrows
    6. Patrick Mitchell
    7. Amirhossein Bakhtiiari
    8. Samantha Stanfield
    9. Els Pardon
    10. H Ronald Kaback
    11. Ruibin Liang
    12. Jan Steyaert
    13. Rosa Viner
    14. Lan Guan
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      In an important study that will be of interest to the mechanistic membrane transport community, the authors capture the first cryo-EM structure of the inward facing melbiose transporter MelB, a well-studied model transporter from the major facilitator (MFS) superfamily. Cryo-EM experiments and supporting biophysical experiments provide solid evidence for transporter conformational changes.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 3 listsLatest version Latest activity
  2. circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA

    This article has 14 authors:
    1. Trine Line Hauge Okholm
    2. Andreas Bjerregaard Kamstrup
    3. Morten Muhlig Nielsen
    4. Anne Kruse Hollensen
    5. Mette Laugesen Graversgaard
    6. Matilde Helbo Sørensen
    7. Lasse Sommer Kristensen
    8. Søren Vang
    9. Samuel S. Park
    10. Gene W. Yeo
    11. Lars Dyrskjøt
    12. Jørgen Kjems
    13. Jakob Skou Pedersen
    14. Christian Kroun Damgaard
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      In this valuable study the authors propose a new regulatory role for one the most abundant circRNAs, circHIPK3, mediated by the RNA binding protein IGF2BP2. While the study presents interesting and largely solid evidence, part of the work is incomplete, requiring additional controls to more robustly support the major claims. The work would also benefit from further discussion addressing the apparently contradictory effects of circHIPK3 and STAT3 depletion in cancer progression.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  3. Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease

    This article has 9 authors:
    1. Kejia Zhang
    2. Patrick Eldin
    3. Jessica H. Ciesla
    4. Laurence Briant
    5. Jenna M. Lentini
    6. Jillian Ramos
    7. Justin Cobb
    8. Joshua Munger
    9. Dragony Fu
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript provides important insights into the degradation of a host tRNA modification enzyme TRMT1 by SARS-CoV-2 protease nsp5. The data convincingly support the main conclusions of the paper. These results will be of interest to virologists interested in studying the alterations in tRNA modifications, host methyltransferases, and viral infections.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  4. Eugenol mimics exercise to promote skeletal muscle fiber remodeling and myokine IL-15 expression by activating TRPV1 channel

    This article has 10 authors:
    1. Tengteng Huang
    2. Xiaoling Chen
    3. Jun He
    4. Ping Zheng
    5. Yuheng Luo
    6. Aimin Wu
    7. Hui Yan
    8. Bing Yu
    9. Daiwen Chen
    10. Zhiqing Huang
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This useful article reports the possible roles of the natural product TRPV1 activator Eugenol on muscle performance and remodeling. It provides as yet incomplete evidence for eugenol, through TRPV1, but nevertheless merits future investigation.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  5. Adenine methylation is very scarce in the Drosophila genome and not erased by the ten-eleven translocation dioxygenase

    This article has 11 authors:
    1. Manon Boulet
    2. Guerric Gilbert
    3. Yoan Renaud
    4. Martina Schmidt-Dengler
    5. Emilie Plantié
    6. Romane Bertrand
    7. Xinsheng Nan
    8. Tomasz Jurkowski
    9. Mark Helm
    10. Laurence Vandel
    11. Lucas Waltzer
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study investigates the presence of DNA adenine methylation (6mA) and the associated function of TET enzyme, a DNA methylation mark eraser, in Drosophila. The study presents valuable findings on the scarcity of 6mA in the Drosophila genome and challenges previous findings regarding the role of TET in 6mA modification. The evidence supporting the claims is solid, and the paper has the potential to stimulate re-evaluations of the significance and regulatory mechanisms of 6mA DNA modifications in Drosophila.

    Reviewed by eLife

    This article has 7 evaluationsAppears in 2 listsLatest version Latest activity
  6. Cryo-EM structure of the CBC-ALYREF complex

    This article has 6 authors:
    1. Bradley P. Clarke
    2. Alexia E. Angelos
    3. Menghan Mei
    4. Pate S. Hill
    5. Yihu Xie
    6. Yi Ren
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important study reports the cryo-electron microscopy structure of a multi-protein complex that recognizes the 5'-end cap of mRNAs and plays a critical role in mRNA export. The structural analyses and biochemical assays in this study provide convincing evidence to support the major claims of the authors, although the inclusion of more functional characterizations in cell-based systems would have strengthened the study. This paper would be of interest to structural biologists and RNA biologists working on mRNA metabolism.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  7. Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation

    This article has 11 authors:
    1. Wayne Mitchell
    2. Ludger J.E. Goeminne
    3. Alexander Tyshkovskiy
    4. Sirui Zhang
    5. Julie Y. Chen
    6. Joao A. Paulo
    7. Kerry A. Pierce
    8. Angelina H. Choy
    9. Clary B. Clish
    10. Steven P. Gygi
    11. Vadim N. Gladyshev
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This valuable study reports comprehensive multi-omic data on the changes induced in young and aged male mouse tail fibroblasts after treatment with chemical reprogramming factors. The authors claim that chemical reprogramming factors induce changes consistent with a reduction of cellular 'biological' age (e.g., correlations with established aging markers in whole tissues). However, the study relies on previously identified aging markers (instead of aging in the tail fibroblast system itself), and thus, at this stage, the evidence in support of the observed molecular changes truly reflecting changes in biological age in the study system is still incomplete.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  8. A cryo-ET study of ciliary rootlet organization

    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This fundamental study offers a compelling molecular model for the organization of rootlets, a critical organelle that links cilia to the basal body, ensuring proper anchoring. While previous research has explored rootlet structure and organization, this study delivers an unprecedented level of resolution, important to the centrosome and cilia field. The model proposed by the authors will serve as a reference for future studies.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  9. Multiple Cullin-Associated E3 Ligases Regulate Cyclin D1 Protein Stability

    This article has 5 authors:
    1. Ke Lu
    2. Ming Zhang
    3. Guozhi Xiao
    4. Liping Tong
    5. Di Chen
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This paper is of interest to cell biologists studying the mechanisms of protein posttranslational modifications. The study investigates Cullin-RING ubiquitin E3 ligases (CRLs) that regulate cyclin D1 protein stability in cells by utilizing siRNA screening and ectopic expression approaches. By screening a siRNA library containing different E3 ligases, the authors identified a previously uncharacterized combination of Cullin 1-7 and associated E3 ligases (Keap1-CUL3, DDB2-CUL4A/4B, WSB2-CUL2/5, and RBX1-CUL1-7) that are important for cyclin D1 ubiquitination and proteasome-mediated degradation.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  10. Protein Kinase Structure and Dynamics: Role of the αC-β4 Loop

    This article has 7 authors:
    1. Jian Wu
    2. Nisha A. Jonniya
    3. Sophia P. Hirakis
    4. Cristina Olivieri
    5. Gianluigi Veglia
    6. Alexandr P. Kornev
    7. Susan S. Taylor
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This valuable study draws attention to the importance of a previously overlooked structural motif in kinase regulation. While the data presented are intriguing and mostly solid, further analysis and additional experiments will be needed in the future to support the authors' hypothesis. The work will be of interest to protein biochemists and enzymologists with an interest in kinases and allostery.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  11. SPAG7 deletion causes intrauterine growth restriction, resulting in adulthood obesity and metabolic dysfunction

    This article has 18 authors:
    1. Stephen E Flaherty
    2. Olivier Bezy
    3. Brianna LaCarubba Paulhus
    4. LouJin Song
    5. Mary Piper
    6. Jincheng Pang
    7. Yoson Park
    8. Shoh Asano
    9. Yu-Chin Lien
    10. John D Griffin
    11. Andrew Robertson
    12. Alan Opsahl
    13. Dinesh Hirenallur-Shanthappa
    14. Youngwook Ahn
    15. Evanthia Pashos
    16. Rebecca A Simmons
    17. Morris J Birnbaum
    18. Zhidan Wu
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study combines molecular genetics and target validation to discover genes involved in obesity and determine their role. It was unanimously agreed that the work is important in terms of significance as it has conceptual and practical implications beyond metabolism, including embryonic and placental development. The strength of evidence is convincing from the use of their forward genetic screen in mice.

    Reviewed by eLife

    This article has 10 evaluationsAppears in 2 listsLatest version Latest activity
  12. PI3Kα inhibition blocks osteochondroprogenitor specification and the hyper-inflammatory response to prevent heterotopic ossification

    This article has 8 authors:
    1. José Antonio Valer
    2. Alexandre Deber
    3. Marius Wits
    4. Carolina Pimenta-Lopes
    5. Marie-José Goumans
    6. José Luis Rosa
    7. Gonzalo Sánchez-Duffhues
    8. Francesc Ventura
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This paper presents valuable insights into the implication of PI3Ka in heterotopic ossification (HO), and illustrates a potential therapeutic efficacy of BYL719 in suppressing HO within a murine model of Fibrodysplasia Ossificans Progressiva. While certain data are novel and compelling, others exhibit redundancies with prior publications and are inadequate in terms of methodology and presentation. Additionally, elucidating the precise molecular mechanisms of BYL719's action is imperative for a comprehensive understanding.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  13. Scaling of an antibody validation procedure enables quantification of antibody performance in major research applications

    This article has 19 authors:
    1. Riham Ayoubi
    2. Joel Ryan
    3. Michael S Biddle
    4. Walaa Alshafie
    5. Maryam Fotouhi
    6. Sara Gonzalez Bolivar
    7. Vera Ruiz Moleon
    8. Peter Eckmann
    9. Donovan Worrall
    10. Ian McDowell
    11. Kathleen Southern
    12. Wolfgang Reintsch
    13. Thomas M Durcan
    14. Claire Brown
    15. Anita Bandrowski
    16. Harvinder Virk
    17. Aled M Edwards
    18. Peter McPherson
    19. Carl Laflamme
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      Antibodies are some of the most critical tools in biomedical research. However, their quality and specificity vary significantly. This fundamental study provides guidelines for how the quality of an antibody should be assessed and recorded and provides compelling data on the selected antibodies. This paper will be of interest to researchers working in experimental cell biology.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  14. An anciently diverged family of RNA binding proteins maintain correct splicing of ultra-long exons through cryptic splice site repression

    This article has 17 authors:
    1. Chileleko Siachisumo
    2. Sara Luzzi
    3. Saad Aldalaqan
    4. Gerald Hysenaj
    5. Caroline Dalgliesh
    6. Kathleen Cheung
    7. Matthew R Gazzara
    8. Ivaylo D Yonchev
    9. Katherine James
    10. Mahsa Kheirollahi Chadegani
    11. Ingrid Ehrmann
    12. Graham R Smith
    13. Simon J Cockell
    14. Jennifer Munkley
    15. Stuart A Wilson
    16. Yoseph Barash
    17. David J Elliott
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study combines CLIP, RNA-seq, and splicing assays with manipulation of RBMX and its homologs RBMY and RBMXL2 to show that the RBMX family suppresses the recognition of cryptic splicing within long exons. The study is important in that it puts forward the intriguing claim that the RBMX family is responsible for the cryptic splice site repression in ultra-long exons. The methods, data, and analyses supporting the claims are solid, broadly supporting the claims, with some weaknesses. The generalization of the findings is somewhat overstated but could be strengthened by deeper statistical integration of the RNA-seq and CLIP datasets.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  15. Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain

    This article has 9 authors:
    1. Gabriella O. Estevam
    2. Edmond M. Linossi
    3. Christian B. Macdonald
    4. Carla A. Espinoza
    5. Jennifer M. Michaud
    6. Willow Coyote-Maestas
    7. Eric A. Collisson
    8. Natalia Jura
    9. James S. Fraser
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript describes a deep mutational scanning study of the kinase domain of the MET receptor tyrosine kinase. The study yields a valuable catalog of essentially all possible deleterious mutations in this portion of the receptor., with convincing evidence. The manuscript will be of interest to researchers working in the field of receptor tyrosine kinases.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  16. Identification of a carbohydrate recognition motif of purinergic receptors

    This article has 8 authors:
    1. Lifen Zhao
    2. Fangyu Wei
    3. Xinheng He
    4. Antao Dai
    5. Dehua Yang
    6. Hualiang Jiang
    7. Liuqing Wen
    8. Xi Cheng
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      Purines are native molecules that affect processes in the immune system, among others. The manuscript describes a valuable investigation of the mode of binding of purines, especially their carbohydrate moiety, to human receptors in cell culture and by computer-based modelling. Solid evidence is presented about the way purines interact with and activate two receptors.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  17. SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes

    This article has 4 authors:
    1. Baira Godneeva
    2. Maria Ninova
    3. Katalin Fejes-Toth
    4. Alexei Aravin
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This important study advances our knowledge of Drosophila Bonus, the sole ortholog of the mammalian transcriptional regulator Tif1. Solid evidence, both in vivo and in vitro, shows how SUMOylation controls the function of the Bonus protein and what the impact of SUMOylation on the function of Bonus protein in the ovary is.

    Reviewed by eLife

    This article has 7 evaluationsAppears in 2 listsLatest version Latest activity
  18. Systematic Analysis of Network-driven Adaptive Resistance to CDK4/6 and Estrogen Receptor Inhibition using Meta-Dynamic Network Modelling

    This article has 3 authors:
    1. Anthony Hart
    2. Sung-Young Shin
    3. Lan K. Nguyen
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript presents a useful method for a comprehensive numerical simulation to systematically characterise the effect of heterogeneity in either the initial conditions or the biophysical parameters on the dynamic behaviour of protein signalling networks. Nevertheless, the presentation and detail of their model appear incomplete to fully support the main claims of the manuscript.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  19. Mitochondrial genomes of Pleistocene megafauna retrieved from recent sediment layers of two Siberian lakes

    This article has 10 authors:
    1. PA Seeber
    2. L Batke
    3. Y Dvornikov
    4. A Schmidt
    5. Y Wang
    6. KR Stoof-Leichsenring
    7. KL Moon
    8. SH Vohr
    9. B Shapiro
    10. LS Epp
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This work presents convincing evidence for the presence of wooly mammoth/rhinoceros ancient environmental DNA (aeDNA) far from the time likely to host living individuals: what is effectively a genetic version of a geological inclusion. These are important findings that will have ramifications for the interpretation and conclusions extracted from aeDNA more generally.

    Reviewed by eLife

    This article has 8 evaluationsAppears in 2 listsLatest version Latest activity
  20. Lactate transporter MCT1 in hepatic stellate cells promotes fibrotic collagen expression in nonalcoholic steatohepatitis

    This article has 17 authors:
    1. Kyounghee Min
    2. Batuhan Yenilmez
    3. Mark Kelly
    4. Dimas Echeverria
    5. Michael Elleby
    6. Lawrence M. Lifshitz
    7. Naideline Raymond
    8. Emmanouela Tsagkaraki
    9. Shauna M. Harney
    10. Chloe DiMarzio
    11. Hui Wang
    12. Nicholas McHugh
    13. Brianna Bramato
    14. Brett Morrision
    15. Jeffery D. Rothstein
    16. Anastasia Khvorova
    17. Michael P. Czech
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This convincing manuscript represents a valuable advance in understanding the role of MCT1 – a transporter for lactate and other organic anions – in hepatocytes and hepatic stellate cells in the liver. The authors also generate exciting new tools to investigate hepatic stellate cell biology, and these may have much broader applications, but future studies are required to validate these new tools.

    Reviewed by eLife

    This article has 9 evaluationsAppears in 2 listsLatest version Latest activity