eLife

Latest preprint reviews

1. Coiled coil control of growth factor and inhibitor-dependent EGFR trafficking and degradation

   This article has 5 authors:

   1. Deepto Mozumdar
   2. Sol Hsun-Hui Chang
   3. Kim Quach
   4. Amy Doerner
   5. Alanna Schepartz

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript investigates the cellular role of the juxtamembrane region in the EGF receptor, a poorly understood portion of the EGFR cytosolic domain that connects the transmembrane segment to the kinase domain. Through a series of well-designed experiments, the work shows that the endocytic trafficking route of EGFR following its activation is determined by the juxtamembrane coiled-coil conformation in a model cell line. This finding is important for three reasons. It identifies a critical role for the juxtamembrane region; it resolves the discrepancy that TGF-beta dissociation from EGFR is supposed to occur at higher pH, yet the EGFR-TGF-beta complex continues to signal from endosomes; and it pinpoints the mechanism of EGFR inhibition by a new class of tyrosine kinase inhibitors.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. All reviewers agreed to share their names with the authors.)

   Reviewed by eLife

2. Alternate patterns of temperature variation bring about very different disease outcomes at different mean temperatures

   This article has 4 authors:

   1. Charlotte Kunze
   2. Pepijn Luijckx
   3. Andrew L Jackson
   4. Ian Donohue

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Kunze et al. provide a fine experiment to show that both increases in mean temperature and (extreme) variability in temperature regimes have important consequences in host-pathogen interactions. The results presented in this manuscript shed a light on why disease spread models fed by experimental data (commonly obtained in stable environmental conditions) are frequently inaccurate. These results lead us to more realistic understanding of the impacts of climate change in biological species but also identify the need of mechanisms behind species interaction in fluctuating environments/temperatures. This manuscript thus comes timely as the planet is warming, and disease ecologists, limnologists, epidemiologists and physiologists are interested in the consequences.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors).

   Reviewed by eLife

3. Radiocarbon and genomic evidence for the survival of Equus Sussemionus until the late Holocene

   This article has 22 authors:

   1. Dawei Cai
   2. Siqi Zhu
   3. Mian Gong
   4. Naifan Zhang
   5. Jia Wen
   6. Qiyao Liang
   7. Weilu Sun
   8. Xinyue Shao
   9. Yaqi Guo
   10. Yudong Cai
   11. Zhuqing Zheng
   12. Wei Zhang
   13. Songmei Hu
   14. Xiaoyang Wang
   15. He Tian
   16. Youqian Li
   17. Wei Liu
   18. Miaomiao Yang
   19. Jian Yang
   20. Duo Wu
   21. Ludovic Orlando
   22. Yu Jiang

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper represents multiple milestones in our understanding of the evolution and extinction of Pleistocene equids, including revising the timing of extinction and clarifying the evolutionary history of Equus (Sussemionus) ovodovi. The discovery of the late persistence of non-caballine equid taxa in northern China until deep into the late Holocene is particularly important. This finding will be of broad interest to the paleontology, paleoecology, archaeology, paleogenomic communities and should stimulate important future research into equid extinction processes.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

   Reviewed by eLife

4. Molecular pathology of the R117H cystic fibrosis mutation is explained by loss of a hydrogen bond

   This article has 2 authors:

   1. Márton A Simon
   2. László Csanády

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Multiple inherited mutations in the epithelial CFTR anion-permeable channel cause cystic fibrosis through different molecular mechanisms that can be targeted by different types of drugs to treat the disease. Drawing from available structural information and double-mutant cycle analysis of patch-clamp recordings, Simon and Csanády find that one of the most common CFTR disease-causing mutations, R117H, disrupts an interaction between the R117 side-chain and a main-chain carbonyl that selectively stabilizes the open state of the channel. These findings may open new paths of exploration for treating patients carrying this mutation, and provide important mechanistic constraints towards understanding the gating mechanism of CFTR proteins.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

   Reviewed by eLife

5. A transcriptional constraint mechanism limits the homeostatic response to activity deprivation in mammalian neocortex

   This article has 11 authors:

   1. Vera Valakh
   2. Derek Wise
   3. Xiaoyue Aelita Zhu
   4. Mingqi Sha
   5. Jaidyn Fok
   6. Stephen D Van Hooser
   7. Robin Schectman
   8. Isabel Cepeda
   9. Ryan Kirk
   10. Sean M O'Toole
   11. Sacha B Nelson

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Homeostatic plasticity helps to confine neural network activity within limits. In this study, the authors show that loss of PAR bZIP family of transcription factors leads to overcompensation of excitatory synaptic transmission and average network activity upon sustained activity deprivation. The work identifies an endogenous transcriptional program that constrains upward homeostatic response and whose activity is implicated in preventing aberrant network activity associated with epilepsy and other brain disorders. These are exciting results that address the question of broad importance. While most arguments are supported by data of high quality, further experiments would strengthen the claims about the relative contribution of excitatory and inhibitory mechanisms and clarify the nature of compensation.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

   Reviewed by eLife

6. Stereospecific lasofoxifene derivatives reveal the interplay between estrogen receptor alpha stability and antagonistic activity in ESR1 mutant breast cancer cells

   This article has 14 authors:

   1. David J Hosfield
   2. Sandra Weber
   3. Nan-Sheng Li
   4. Madline Sauvage
   5. Carstyn F Joiner
   6. Govinda R Hancock
   7. Emily A Sullivan
   8. Estelle Ndukwe
   9. Ross Han
   10. Sydney Cush
   11. Muriel Lainé
   12. Sylvie C Mader
   13. Geoffrey L Greene
   14. Sean W Fanning

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper will be of broad interest to many fields, including drug discovery, cancer biology, and structure biology. It makes a significant advance in understanding the mechanism of action of hormone therapies for breast cancer, and how resistance driving mutations alter drug responses. The structural biology data has clear potential for strong impact though some additional analysis might be needed.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

   Reviewed by eLife

7. Cnidarian hair cell development illuminates an ancient role for the class IV POU transcription factor in defining mechanoreceptor identity

   This article has 7 authors:

   1. Ethan Ozment
   2. Arianna N Tamvacakis
   3. Jianhong Zhou
   4. Pablo Yamild Rosiles-Loeza
   5. Esteban Elías Escobar-Hernandez
   6. Selene L Fernandez-Valverde
   7. Nagayasu Nakanishi

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript focusses on a little studied, but highly interesting presumptive mechanosensory cell type in cnidarians, the 'hair cell'. The work shows that the POU-IV transcription factor is required for the maturation of this cell type in the sea anemone Nematostella vectensis. Because POU-IV transcription factors also play essential roles in the differentiation of mechanoreceptors in many bilaterian phyla, this suggests an evolutionarily ancient role of POU-IV in regulating mechanosensory identity. This study will hence be of great interest to developmental biologists and evolutionary biologists who are interested in the developmental evolution of neuronal cell types.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

   Reviewed by eLife

8. Allosteric modulation of the adenosine A2A receptor by cholesterol

   This article has 9 authors:

   1. Shuya Kate Huang
   2. Omar Almurad
   3. Reizel J Pejana
   4. Zachary A Morrison
   5. Aditya Pandey
   6. Louis-Philippe Picard
   7. Mark Nitz
   8. Adnan Sljoka
   9. R Scott Prosser

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Cholesterol has long been known to have significant effects on G protein-coupled receptor (GPCR) ligand binding properties and stability, and cholesterol/GPCR interactions have frequently been observed in high-resolution structures. However, relatively limited biophysical work has been done to investigate the mechanistic basis for cholesterol's effects. This manuscript describes the use of a sensitive 19F NMR probe to monitor conformational equilibria in a prototypical GPCR, the A2a adenosine receptor. These experiments, together with data from other NMR experiments, computational analysis, and G protein assays, show that the subtle effects of cholesterol derive in large part from modulation of membrane biophysical properties, in contrast to conventional allosteric modulators that exert their effects through direct long-lived receptor binding.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

   Reviewed by eLife

9. Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges

   This article has 13 authors:

   1. Elliot H Smith
   2. Jyun-you Liou
   3. Edward M Merricks
   4. Tyler Davis
   5. Kyle Thomson
   6. Bradley Greger
   7. Paul House
   8. Ronald G Emerson
   9. Robert Goodman
   10. Guy M McKhann
   11. Sameer Sheth
   12. Catherine Schevon
   13. John D Rolston

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Smith et al. describes the propagation patterns of electrical activity in the brains of human epileptic patients. The authors demonstrate that interictal spikes, commonly observed electrical events in epileptic patients, propagate in a similar manner to seizures. This suggests that interictal spikes could be used in surgical planning, which would be of great interest to neurosurgeons and neurologists treating patients with medication refractory epilepsy.

     (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

   Reviewed by eLife

10. Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos

    This article has 7 authors:

    1. Graham JM Hickey
    2. Candice L Wike
    3. Xichen Nie
    4. Yixuan Guo
    5. Mengyao Tan
    6. Patrick J Murphy
    7. Bradley R Cairns

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      This manuscript is of broad interest to developmental biologists and those studying transcriptional/epigenetic regulation of cell-specific and housekeeping gene programs. The work demonstrates that Polycomb complexes coordinate the regulation of distinct groups of genes during early embryogenesis, which offers interesting insights into how very early embryos differentially control housekeeping versus specific developmental gene promoters/enhancers. The data are of high quality, and the conclusions are insightful yet measured.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

    Reviewed by eLife