Biophysics

Unsupervised Bayesian Ising Approximation for decoding neural activity and other biological dictionaries

1. Damián G Hernández
2. Samuel J Sober
3. Ilya Nemenman

• Curated by eLife

  Evaluation Summary:

  Hernandez et al use an elegant mathematical framework to build a novel tool for extracting unusually frequent (or infrequent) patterns in multidimensional biological data when only a small number of measurements are available. This is a common problem in many biological settings, so the tool could potentially be used to answer a wide range of statistically hard questions. As a first demonstration of its use, the authors show that the new tool can be used to reveal novel properties about neural responses in zebra finches during song generation.

  (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

Conformational decoupling in acid-sensing ion channels uncovers mechanism and stoichiometry of PcTx1-mediated inhibition

1. Stephanie A Heusser
2. Christian B Borg
3. Janne M Colding
4. Stephan A Pless

• Curated by eLife

  Evaluation Summary:

  This work provides direct evidence that PcTx1, a modulator commonly used to study acid-sensing ion channels, induces a conformational change that persists long after an effect on the channel activity has dissipated. The data support this central claim of the paper and invite future investigation of the precise mechanism. The work is of general interest to those studying ion channel biophysics and pharmacology and is a fine example of the power of combined functional and fluorescence measurements.

  (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

Molecular insights into the differential dynamics of SARS-CoV-2 variants of concern

1. Nabanita Mandal
2. Aditya K. Padhi
3. Soumya Lipsa Rath

Reviewed by ScreenIT

Enhanced specificity mutations perturb allosteric signaling in CRISPR-Cas9

1. Lukasz Nierzwicki
2. Kyle W East
3. Uriel N Morzan
4. Pablo R Arantes
5. Victor S Batista
6. George P Lisi
7. Giulia Palermo

• Curated by eLife

  Evaluation Summary:

  This is a comprehensive study combining solution NMR with molecular dynamics simulations to uncover the effects of three key mutations in the Cas9 HNH domain that increase CRISP-Cas9 complex specificity and reduce off-target activity. Through the analysis of these three different mutations, the authors concluded that by tuning the conformational dynamics of the HNH module in the CRISP-Cas9 complex, it is possible to control the function and specificity of the system. Combined these findings could have important implications for the design of new variants for this important gene editing complex.

  (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

Physical observables to determine the nature of membrane-less cellular sub-compartments

1. Mathias L Heltberg
2. Judith Miné-Hattab
3. Angela Taddei
4. Aleksandra M Walczak
5. Thierry Mora

• Curated by eLife

  Evaluation Summary:

  There has been a lively debate recently concerning the multiplicity of reported observations of phase-separated compartments inside of cells. Specifically, some claims of phase separation have been challenged, and an alternative model put forward in which clustering of observed particles is due to a clustering of binding sites with no phase separation. The current study does an admirable job of proposing and analyzing ways of distinguishing these two scenarios.

  (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

Intelligent Resolution: Integrating Cryo-EM with AI-driven Multi-resolution Simulations to Observe the SARS-CoV-2 Replication-Transcription Machinery in Action

1. Anda Trifan
2. Defne Gorgun
3. Zongyi Li
4. Alexander Brace
5. Maxim Zvyagin
6. Heng Ma
7. Austin Clyde
8. David Clark
9. Michael Salim
10. David J. Hardy
11. Tom Burnley
12. Lei Huang
13. John McCalpin
14. Murali Emani
15. Hyenseung Yoo
16. Junqi Yin
17. Aristeidis Tsaris
18. Vishal Subbiah
19. Tanveer Raza
20. Jessica Liu
21. Noah Trebesch
22. Geoffrey Wells
23. Venkatesh Mysore
24. Thomas Gibbs
25. James Phillips
26. S. Chakra Chennubhotla
27. Ian Foster
28. Rick Stevens
29. Anima Anandkumar
30. Venkatram Vishwanath
31. John E. Stone
32. Emad Tajkhorshid
33. Sarah A. Harris
34. Arvind Ramanathan

Reviewed by ScreenIT

Low-affinity integrin states have faster ligand-binding kinetics than the high-affinity state

1. Jing Li
2. Jiabin Yan
3. Timothy A Springer

• Curated by eLife

  Evaluation Summary:

  Li, Yan and Springer report ligand binding on- and off-rates for three different conformations of α4β1 as well as α5β1 integrin. This is the first report that provides these numbers, which are important to understand the 'mode of integrin activation'. The study is - from a technical stand point - flawlessly performed and the calculated data is in perfect agreement with the previously published data.

  (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

A mechano-osmotic feedback couples cell volume to the rate of cell deformation

1. Larisa Venkova
2. Amit Singh Vishen
3. Sergio Lembo
4. Nishit Srivastava
5. Baptiste Duchamp
6. Artur Ruppel
7. Alice Williart
8. Stéphane Vassilopoulos
9. Alexandre Deslys
10. Juan Manuel Garcia Arcos
11. Alba Diz-Muñoz
12. Martial Balland
13. Jean-François Joanny
14. Damien Cuvelier
15. Pierre Sens
16. Matthieu Piel

• Curated by eLife

  Evaluation Summary:

  The paper by Venkova et al. is a comprehensive study of mammalian cell volume dynamics during the common cellular process of adhesion and spreading on a flat substrate, osmotic changes, and mechanical confinement. The paper reveals a complex interplay between cell water/ion regulation, cytoskeletal processes, and mechanical deformation of the cell. The topic is important in cell physiology and should be of considerable interest to cell biologists, mechanobiologists and biophysicists.

  (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

The pathogen-encoded signalling receptor Tir exploits host-like intrinsic disorder for infection

1. Marta F. M. Vieira
2. Guillem Hernandez
3. Qiyun Zhong
4. Miguel Arbesú
5. Tiago Veloso
6. Tiago Gomes
7. Maria L. Martins
8. Hugo Monteiro
9. Carlos Frazão
10. Gad Frankel
11. Andreas Zanzoni
12. Tiago N. Cordeiro

Reviewed by Review Commons

How Does Temperature Affect the Dynamics of SARS-CoV-2 M Proteins? Insights from Molecular Dynamics Simulations

1. Soumya Lipsa Rath
2. Madhusmita Tripathy
3. Nabanita Mandal

Reviewed by ScreenIT