eLife

Latest preprint reviews

1. Autosomal Allelic Inactivation: Variable Replication and Dosage Sensitivity

   This article has 9 authors:

   1. Michael B. Heskett
   2. Athanasios E. Vouzas
   3. Brian Johnstone
   4. Krister P. Freese
   5. Phillip A. Yates
   6. Philip F. Copenhaver
   7. Paul T. Spellman
   8. David M. Gilbert
   9. Mathew J. Thayer

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study links allelic expression imbalance with replication timing, suggesting a stochastic model for haploinsufficiency in dosage-sensitive disease. The integration of allele-specific RNA-seq and replication timing in clonal systems provides solid evidence for an association between asynchronous replication and allelic imbalance, although the scope and generality of some conclusions require more cautious interpretation. This study will interest epigeneticists and genome regulation researchers studying replication timing and monoallelic expression, as well as developmental biologists and human geneticists concerned with clonal heterogeneity, haploinsufficiency, and variable disease penetrance.

     [Editors' note: this paper was reviewed by Review Commons.]

   Reviewed by eLife

2. The transcription factor BCL11A restores differentiation potential to aged oligodendrocyte progenitor cells

   This article has 6 authors:

   1. Tanay Ghosh
   2. Roey Baror
   3. Chao Zhao
   4. Amar Sharma
   5. Nick Goldman
   6. Robin JM Franklin

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This valuable study demonstrates molecular changes associated with age related impairment in oligodendrocyte differentiation and ability to myelinate. The identification of particular genes that are associated with this decline will provide potential future targets for therapeutic interventions. The reviewers felt that the quality of the evidence was solid while identifying some minor weaknesses that if addressed would enhance the rigor of the study.

   Reviewed by eLife

3. Structural basis for the folding of PINK1 by the HSP90–CDC37 chaperone complex

   This article has 8 authors:

   1. Kei Okatsu
   2. Hayato Yamamoto
   3. Akinori Okamoto
   4. Shinya H. Goto
   5. Yumiko Nishimoto
   6. Yukihiko Sugita
   7. Takeshi Noda
   8. Shuya Fukai

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study presents a high-quality cryo-EM structure of the human kinase PINK1 in complex with the HSP90-CDC37 chaperone complex, capturing a partially folded intermediate in which the C-lobe and C-terminal extension are structured while the N-lobe remains unfolded and engaged by the HSP90 clamp. The structural data are broadly consistent with a recently published structure of the same complex, providing useful insight into early steps of PINK1 maturation and highlighting residues linked to familial Parkinson's disease. However, the mechanistic conclusions remain incomplete because the manuscript does not experimentally validate key hypotheses raised by the structure, including the functional roles of the C-lobe interface, the HPNI motif, the C-terminal extension, or the proposed competition between HSP90 and TOM20.

   Reviewed by eLife

4. RNA Selectively Modulates Activity of Virulent Amyloid PSMα3 and Host Defense LL-37 via Phase Separation and Aggregation Dynamics

   This article has 12 authors:

   1. Bader Rayan
   2. Eilon Barnea
   3. Rinat Indig
   4. Christian F Pantoja
   5. Jesse Gayk
   6. Yael Lupu- Haber
   7. Alexander Upcher
   8. Amir Argoetti
   9. Jacob Aunstrup Larsen
   10. Alexander K Buell
   11. Markus Zweckstetter
   12. Meytal Landau

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study investigates how RNA molecules modulate phase separation, aggregation, and cytotoxicity of the staphylococcal virulent peptide PSMα3 and the human host‑defence peptide LL‑37 using an array of biophysical and cell‑based assays. If validated, these findings would be important, as they suggest that nucleic acids can tune the material state and bioactivity of amyloids, with implications for host-pathogen interactions and for the design of therapeutics that target phase behaviour. However, the evidence is incomplete: many key claims rest on qualitative imaging and contested assumptions about "functional" amyloids, and the absence of quantitative binding data, phase diagrams, and appropriate controls limits confidence in the conclusions.

   Reviewed by eLife

5. Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons

   This article has 3 authors:

   1. Daniel Beaudet
   2. Christopher L Berger
   3. Adam G Hendricks

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     In their valuable study, Beaudet, Berger and Hendricks provide a mechanistic link between disease-associated tau hyperphosphorylation, loss of cooperative tau envelope formation on microtubules, and dysregulation of axonal transport prior to aggregation. Using complementary in vitro reconstitution and human iPSC-derived neuronal assays with phosphodeficient and phosphomimetic tau constructs targeting 14 disease-relevant sites, the authors convincingly show that phosphorylation state alters tau organization on microtubules and differentially impacts kinesin- and lysosome-based transport. The evidence is solid and well aligned with the conclusions, yet the work could be further strengthened by incorporating additional controls and motor-specific assays to refine the mechanistic depth.

   Reviewed by eLife

6. Ventral Hippocampal Temporoammonic and Schaffer Collateral Pathways Differentially Control Fear- and Anxiety-Related Behaviors

   This article has 6 authors:

   1. Maltesh Kambali
   2. Muxiao Wang
   3. Rajasekar Nagarajan
   4. Jinrui Lyu
   5. Howard Gritton
   6. Uwe Rudolph

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     Kambali et al use optogenetic manipulations to examine whether the ventral hippocampal Schaffer collateral (vCA3-to-vCA1) and temporoammonic (EC-to-vCA1) pathways regulate anxiety- and fear-related behaviors in mice. They find that both pathways regulate the expression of fear (freezing) responses to a context and auditory conditioned stimulus paired with foot shock (trace conditioning protocol), but only the Schaffer collateral pathway regulates the expression of anxiety-related behaviors in the elevated plus maze, open field test, and Vogel conflict test. Overall, the study is valuable: it detects bidirectional effects of optogenetic excitation and inhibition in both pathways. However, the strength of the evidence in support of its main claims is incomplete.

   Reviewed by eLife

7. The type VI secretion system governs strain maintenance in a wild mammalian gut microbiome

   This article has 13 authors:

   1. Beth A Shen
   2. Kyle L Asfahl
   3. Bentley Lim
   4. Savannah K Bertolli
   5. Samuel S Minot
   6. Matthew C Radey
   7. Kelsi Penewit
   8. Billy Ngo
   9. Stephen J Salipante
   10. Christopher D Johnston
   11. S Brook Peterson
   12. Andrew L Goodman
   13. Joseph D Mougous

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This fundamental work significantly advances our understanding of how contact-dependent antagonism enables keystone bacteria to establish and maintain their niche over time. The evidence obtained is convincing, supporting most of the conclusions drawn. This work will be of significant interest to the microbiome research community.

   Reviewed by eLife

8. Cytoplasmatic polyadenylation of mRNA by TENT5A is critical for enamel mineralization

   This article has 15 authors:

   1. Goretti Aranaz-Novaliches
   2. Olga Gewartowska
   3. Frantisek Spoutil
   4. Seweryn Mroczek
   5. Pavel Talacko
   6. Karel Harant
   7. Ana-Matilde Augusto-Vale
   8. Irena Krejzova
   9. Carlos Eduardo Madureira Trufen
   10. Pawel Krawczyk
   11. Ales Benda
   12. Vendula Novosadová
   13. Radislav Sedlacek
   14. Andrzej Dziembowski
   15. Jan Prochazka

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study reports an important and novel finding that TENT5A, an enzyme involved in fine-tuning poly(A) tail length on selected mRNAs, is required for proper enamel mineralization in mice. The evidence supporting the authors' conclusion that reduced expression of enamel matrix proteins (EMPs) in TENT5A-deficient mice results from shortened poly(A) tails remains incomplete, as TENT5A may possess additional functions independent of post-transcriptional regulation that are not addressed in the current study.

   Reviewed by eLife

9. Strong mnemonic prediction errors increase cognitive control, attention, and arousal

   This article has 4 authors:

   1. Alice M Xue
   2. Jenna Jokhani
   3. Anthony M Norcia
   4. Anthony D Wagner

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study characterizes a cascade of neural processes triggered by memory-based prediction errors. The study uses an impressive collection of approaches and methods to characterize and measure cognitive control, arousal, and memory changes as a function of memory-based violations. The analyses are technically sophisticated and rigorous and, taken together, provide solid evidence that there are multiple processes accompanying prediction errors, and that they differentially relate to successful encoding. The manuscript would be much improved by the addition of a discussion or visual schematic that integrates the numerous findings together into a more coherent model.

   Reviewed by eLife

10. Opposite and complementary roles of the two calcium thresholds for inducing LTP and LTD in models of striatal projection neurons

    This article has 1 author:

    1. Daniel Trpevski

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This computational study constitutes an extension to prior work on biophysical calcium-based synaptic plasticity rules with metaplasticity, investigating how single neurons can learn to perform non-linear pattern classification. This important work presents a significantly simpler solution to the studied problem with potentially broad applicability, there is however incomplete evidence to support the core conclusions.

    Reviewed by eLife