Biophysics

  1. Label-free imaging of M1 and M2 macrophage phenotypes in the human dermis in vivo using two-photon excited FLIM

    1. Marius Kröger
    2. Jörg Scheffel
    3. Evgeny A Shirshin
    4. Johannes Schleusener
    5. Martina C Meinke
    6. Jürgen Lademann
    7. Marcus Maurer
    8. Maxim E Darvin

    • Curated by eLife

      Evaluation Summary:

      Kröger et al use 2-photon FLIM tomography to perform correlative imaging on in vitro, ex vivo and in vivo blood and skin cells to determine characteristic NADPH fluorescence lifetimes for M1 and M2 ends of macrophage spectrum. Interestingly, M1 and M2 macrophages, and all other tissue cells, had distinctive lifetime features leading to robust prediction of phenotypes, with ground trust defined by cytokine staining. They generate a decision tree that has ~90% accuracy in identifying M1 and M2 based on FLIM parameters and additional information. The ability to use two photon fluorescence lifetime tomography of NADPH fluorescence to identify macrophages and their inflammatory status in human tissues should open opportunities in experimental medicine and eventually medical diagnosis.

      (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

    2 evaluationsAppears in 1 listLatest version Latest activity

  2. The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism

    1. Elena B. Riel
    2. Björn C. Jürs
    3. Sönke Cordeiro
    4. Marianne Musinszki
    5. Marcus Schewe
    6. Thomas Baukrowitz

    Reviewed by Biophysics Colab

    1 evaluationAppears in 2 listsLatest version Latest activity

  3. Allosteric modulation of the adenosine A2A receptor by cholesterol

    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

    • 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

    5 evaluationsAppears in 1 listLatest version Latest activity

  4. pH-dependent 11° F1FO ATP synthase sub-steps reveal insight into the FO torque generating mechanism

    1. Seiga Yanagisawa
    2. Wayne D Frasch

    • Curated by eLife

      Evaluation Summary:

      This paper is of outstanding interest to the broad community of scientists interested in biological energy conversion in general and rotary ATPases in particular. The authors show that the 36{degree sign} power stroke in ATP synthesis is subdivided into two steps of 11{degree sign} and 25{degree sign} in the E. coli enzyme, which serves as a comparatively simple model of the fundamental and universally important process of ATP production in mitochondria and chloroplasts. By combining precise and sophisticated single-molecule studies with directed mutagenesis, this work provides the much-needed functional context for recent high-resolution cryo-EM structures of rotary ATPases.

      (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

    5 evaluationsAppears in 1 listLatest version Latest activity

  5. #COVIDisAirborne: AI-Enabled Multiscale Computational Microscopy of Delta SARS-CoV-2 in a Respiratory Aerosol

    1. Abigail Dommer
    2. Lorenzo Casalino
    3. Fiona Kearns
    4. Mia Rosenfeld
    5. Nicholas Wauer
    6. Surl-Hee Ahn
    7. John Russo
    8. Sofia Oliveira
    9. Clare Morris
    10. Anthony Bogetti
    11. Anda Trifan
    12. Alexander Brace
    13. Terra Sztain
    14. Austin Clyde
    15. Heng Ma
    16. Chakra Chennubhotla
    17. Hyungro Lee
    18. Matteo Turilli
    19. Syma Khalid
    20. Teresa Tamayo-Mendoza
    21. Matthew Welborn
    22. Anders Christensen
    23. Daniel G. A. Smith
    24. Zhuoran Qiao
    25. Sai Krishna Sirumalla
    26. Michael O’Connor
    27. Frederick Manby
    28. Anima Anandkumar
    29. David Hardy
    30. James Phillips
    31. Abraham Stern
    32. Josh Romero
    33. David Clark
    34. Mitchell Dorrell
    35. Tom Maiden
    36. Lei Huang
    37. John McCalpin
    38. Christopher Woods
    39. Alan Gray
    40. Matt Williams
    41. Bryan Barker
    42. Harinda Rajapaksha
    43. Richard Pitts
    44. Tom Gibbs
    45. John Stone
    46. Daniel Zuckerman
    47. Adrian Mulholland
    48. Thomas Miller
    49. Shantenu Jha
    50. Arvind Ramanathan
    51. Lillian Chong
    52. Rommie Amaro

    Reviewed by ScreenIT

    1 evaluationAppears in 1 listLatest version Latest activity

  6. Drug targeting Nsp1-ribosomal complex shows antiviral activity against SARS-CoV-2

    1. Mohammad Afsar
    2. Rohan Narayan
    3. Md Noor Akhtar
    4. Deepakash Das
    5. Huma Rahil
    6. Santhosh Kambaiah Nagaraj
    7. Sandeep M Eswarappa
    8. Shashank Tripathi
    9. Tanweer Hussain

    • Curated by eLife

      Evaluation Summary:

      This work reports on a drug repurposing effort to target the non-structural protein 1 (Nsp1) of SARS-Cov-2, involved in suppressing host immune function. The authors use a combination of computational, in vitro and cellular assays to this end. They start by virtual screening of an FDA approved drug library, followed by biophysical assays to measure the binding affinity of the top hits as well as molecular dynamics simulations and free energy calculations to confirm binding poses. Finally, in vitro and cellular assays were used to quantify translation inhibition and rescue as well as the production of infectious virus particles. One of the FDA approved drugs, Montelukast, emerges as a promising antiviral drug candidate.

      (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, ScreenIT

    5 evaluationsAppears in 3 listsLatest version Latest activity

  7. Conformational dynamics and allosteric modulation of the SARS-CoV-2 spike

    1. Marco A Díaz-Salinas
    2. Qi Li
    3. Monir Ejemel
    4. Leonid Yurkovetskiy
    5. Jeremy Luban
    6. Kuang Shen
    7. Yang Wang
    8. James B Munro

    • Curated by eLife

      Evaluation Summary:

      This manuscript describes timely work on the structural dynamics of the SARS-CoV-2 spike protein that will be of importance to a broad range of scientists with interests in the biology of SARS-CoV-2 and COVID-19 and the function of anti-COVID-19 vaccines and antibodies as well as to molecular biophysicists generally interested in single-molecule imaging, protein dynamics, allostery, and molecular mechanisms. The experiments were very well-designed, controlled, and executed, and the data are of very high quality. Nonetheless, although the conclusions seem to be generally supported by the data and consistent with expectations based on previous findings, there are some concerns regarding the modeling and error analysis of some of the 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 #2 agreed to share their name with the authors.)

    Reviewed by eLife, ScreenIT

    4 evaluationsAppears in 2 listsLatest version Latest activity

  8. Ensemble cryo-electron microscopy reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex

    1. James Chen
    2. Qi Wang
    3. Brandon Malone
    4. Eliza Llewellyn
    5. Yakov Pechersky
    6. Kashyap Maruthi
    7. Ed T. Eng
    8. Jason K. Perry
    9. Elizabeth A. Campbell
    10. David E. Shaw
    11. Seth A. Darst

    Reviewed by ScreenIT

    1 evaluationAppears in 1 listLatest version Latest activity

  9. Analyzing SARS CoV-2 Patient Data Using Quantum Supervised Machine Learning

    1. Zara Yu

    Reviewed by ScreenIT

    1 evaluationAppears in 1 listLatest version Latest activity

  10. Structural Basis of the Main Proteases of Coronavirus Bound to Drug Candidate PF-07321332

    1. Jian Li
    2. Cheng Lin
    3. Xuelan Zhou
    4. Fanglin Zhong
    5. Pei Zeng
    6. Yang Yang
    7. Yuting Zhang
    8. Bo Yu
    9. Xiaona Fan
    10. Peter J. McCormick
    11. Rui Fu
    12. Yang Fu
    13. Haihai Jiang
    14. Jin Zhang

    Reviewed by ScreenIT

    1 evaluationAppears in 1 listLatest version Latest activity
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