eLife

Latest preprint reviews

1. The deep-rooted origin of disulfide-rich spider venom toxins

   This article has 2 authors:

   1. Naeem Yusuf Shaikh
   2. Kartik Sunagar

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This is an important survey of disulfide-rich peptides (DRPs), which comprise a large fraction of the most functionally important components of spider venom. While spider DRPs were thought to have evolved independently numerous times throughout the spider tree of life, the authors make a solid case for the idea that they all stem from a single common ancestral protein. The study makes a significant advance towards formalizing the diversity of spider venoms, which will be of interest both to scientists working on protein evolution and to those working on functional venomics.

   Reviewed by eLife

2. The anti-caspase 1 inhibitor VX-765 reduces immune activation, CD4+ T cell depletion, viral load, and total HIV-1 DNA in HIV-1 infected humanized mice

   This article has 7 authors:

   1. Mathieu Amand
   2. Philipp Adams
   3. Rafaela Schober
   4. Gilles Iserentant
   5. Jean-Yves Servais
   6. Michel Moutschen
   7. Carole Seguin-Devaux

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     The present study presents the important finding that HIV infection activates the NLRP3, IFI16, and AIM 2 inflammasome pathways and that treatment with the anti-caspase 1 inhibitor VX-765 moderately reduces inflammasome activation and CD4 T cell depletion in a humanized NSG mouse model. The evidence supporting that inflammasome activation may play an important role in CD4 T cell depletion and that anti-caspase-1 inhibitors may reduce harmful inflammation is for the most part solid, although not always complete. The results will be of interest to scientists and physicians working on HIV immunology, pathogenesis and cure strategies.

   Reviewed by eLife

3. The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation

   This article has 12 authors:

   1. Xiao-Lan Liu
   2. Yulin Yang
   3. Yue Hu
   4. Jingjing Wu
   5. Chuqiao Han
   6. Qiaojia Lu
   7. Xihui Gan
   8. Shaohua Qi
   9. Jinhu Guo
   10. Qun He
   11. Yi Liu
   12. Xiao Liu

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This important study provides evidence for CPC-3 mediating induction of the transcription factor CPC-1 in starved Neurospora cells, with CPC-1-mediated recruitment of Gcn5 and acetylation of the FRQ promoter counteracting the function of histone deacetylase HDA1, which in turn maintains high occupancy of the transcription factor WCC and attendant circadian rhythm of FRQ expression. The findings are significant in showing how the well-established pathways for circadian rhythm centered on FRQ gene expression and cross-pathway control centered on CPC-1 induction are integrated to maintain rhythmic cell growth in the face of amino acid limitation. However, the evidence for these claims is incomplete in certain respects and additional statistical analyses and experimental evidence are needed to better support the claims of rhythmic CPC-1 binding at FRQ, of the role of GCN-5 in rhythmic FRQ transcription in starvation conditions, and of rhythmic transcription of CPC-1-regulated amino acid biosynthetic genes.

   Reviewed by eLife

4. Exploring therapeutic strategies for infantile neuronal axonal dystrophy (INAD/PARK14)

   This article has 13 authors:

   1. Guang Lin
   2. Burak Tepe
   3. Geoff McGrane
   4. Regine C Tipon
   5. Gist Croft
   6. Leena Panwala
   7. Amanda Hope
   8. Agnes JH Liang
   9. Zhongyuan Zuo
   10. Seul Kee Byeon
   11. Lily Wang
   12. Akhilesh Pandey
   13. Hugo J Bellen

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This work is of significant interest to those studying neurodegeneration, demonstrating key pathologies in PLA2G6-associated disease in both patient-derived neuronal models and a novel trans heterozygote mouse model. Moreover, it identifies a number of possible compounds that could potentially be re-purposed for therapeutic use in PLA2G6-associated neurodegeneration. Lastly, it shows a proof-of-principle in a mouse model that gene therapy with human PLA2G6 can rescue defects in PLA2G6 deficiency. Whilst the majority of the data are solid and convincing, there are a number of consolidatory experiments that would add greatly to the overall impact and novelty of the work.

   Reviewed by eLife

5. Drug specificity and affinity are encoded in the probability of cryptic pocket opening in myosin motor domains

   This article has 10 authors:

   1. Artur Meller
   2. Jeffrey M Lotthammer
   3. Louis G Smith
   4. Borna Novak
   5. Lindsey A Lee
   6. Catherine C Kuhn
   7. Lina Greenberg
   8. Leslie A Leinwand
   9. Michael J Greenberg
   10. Gregory R Bowman

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This important study presents insights into how conformational dynamics differentially influences drug specificity and affinity in myosin isoforms using computational approaches. The evidence supporting the conclusions is convincing, establishing a relationship between inhibition and protein dynamics using state of the art computational techniques followed by experimental validation. The work will be of broad interest to computational biophysicists and medicinal chemists.

   Reviewed by eLife

6. Emergent dynamics of adult stem cell lineages from single nucleus and single cell RNA-Seq of Drosophila testes

   This article has 24 authors:

   1. Amelie A Raz
   2. Gabriela S Vida
   3. Sarah R Stern
   4. Sharvani Mahadevaraju
   5. Jaclyn M Fingerhut
   6. Jennifer M Viveiros
   7. Soumitra Pal
   8. Jasmine R Grey
   9. Mara R Grace
   10. Cameron W Berry
   11. Hongjie Li
   12. Jasper Janssens
   13. Wouter Saelens
   14. Zhantao Shao
   15. Chun Hu
   16. Yukiko M Yamashita
   17. Teresa Przytycka
   18. Brian Oliver
   19. Julie A Brill
   20. Henry Krause
   21. Erika L Matunis
   22. Helen White-Cooper
   23. Stephen DiNardo
   24. Margaret T Fuller

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This study provides further detailed analysis of recently published Fly Atlas data supplemented with newly generated single cell RNA-seq data. Through characterizing these datasets, the authors define different germ cell and somatic cell clusters throughout the testis. This work confirms and extends previous observations regarding the changing gene expression programs these cells exhibit during their differentiation. This manuscript provides an important and detailed foundation for future studies of these lineages.

   Reviewed by eLife

7. Reserpine maintains photoreceptor survival in retinal ciliopathy by resolving proteostasis imbalance and ciliogenesis defects

   This article has 14 authors:

   1. Holly Y Chen
   2. Manju Swaroop
   3. Samantha Papal
   4. Anupam K Mondal
   5. Hyun Beom Song
   6. Laura Campello
   7. Gregory J Tawa
   8. Florian Regent
   9. Hiroko Shimada
   10. Kunio Nagashima
   11. Natalia de Val
   12. Samuel G Jacobson
   13. Wei Zheng
   14. Anand Swaroop

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This work provides an important pipeline for high-throughput screening platform to be used for drug discovery. The current data are incomplete. Further validation of human patients-derived iPSC clones and functional assays in mice will strengthen the conclusion.

   Reviewed by eLife

8. Recessive pathogenic variants in MCAT cause combined oxidative phosphorylation deficiency

   This article has 13 authors:

   1. Bryn D Webb
   2. Sara M Nowinski
   3. Ashley Solmonson
   4. Jaya Ganesh
   5. Richard J Rodenburg
   6. Joao Leandro
   7. Anthony Evans
   8. Hieu S Vu
   9. Thomas P Naidich
   10. Bruce D Gelb
   11. Ralph J DeBerardinis
   12. Jared Rutter
   13. Sander M Houten

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This paper is a first report of a human subject with an MCAT mutation showing reduced mitochondrial activity, but without defining the molecular mechanism connecting the loss of MCAT activity to mitochondrial dysfunction. It adds to the important field of mitochondrial disease genes and how they impact human physiology.

   Reviewed by eLife

9. A hierarchy of cell death pathways confers layered resistance to shigellosis in mice

   This article has 8 authors:

   1. Justin L Roncaioli
   2. Janet Peace Babirye
   3. Roberto A Chavez
   4. Fitty L Liu
   5. Elizabeth A Turcotte
   6. Angus Y Lee
   7. Cammie F Lesser
   8. Russell E Vance

   This article has been curated by 1 group:

   • Curated by eLife

     eLife assessment

     This paper reports important findings on the mechanisms by which death pathways are activated by Shigella infection to impact the host response. The methods used provide compelling evidence for the involvement of multiple death cell pathways in the pathogenesis and host response to murine shigellosis. The results presented therein will be of interest to investigators in the field of bacterial pathogenesis, infectious disease and immunology.

   Reviewed by eLife

10. Tyramine and its Amtyr1 receptor modulate attention in honey bees (Apis mellifera)

    This article has 11 authors:

    1. Joseph S Latshaw
    2. Reece E Mazade
    3. Mary Petersen
    4. Julie A Mustard
    5. Irina Sinakevitch
    6. Lothar Wissler
    7. Xiaojiao Guo
    8. Chelsea Cook
    9. Hong Lei
    10. Jürgen Gadau
    11. Brian Smith

    This article has been curated by 1 group:

    • Curated by eLife

      eLife assessment:

      This article reports the fundamental discovery that interfering with the function of the tyramine receptor causes a rapid decline in responses to olfactory stimuli in the honey bee. While tyramine signaling might specifically control the process of latent inhibition without affecting appetitive conditioning, the present analysis is incomplete in terms of ruling out the possibility that tyramine affects other functions of the antennal lobe. Nonetheless, compelling data highlight the role of one of the most highly expressed biogenic amine receptors in the insect olfactory system.

    Reviewed by eLife