Physiology

Topography and motion of acid-sensing ion channel intracellular domains

1. Tyler Couch
2. Kyle D Berger
3. Dana L Kneisley
4. Tyler W McCullock
5. Paul Kammermeier
6. David M Maclean

• Curated by eLife

  Evaluation Summary:

  This is a rigorous and clearly written paper that provides quantitative data for the scope of intracellular signalling by ASIC channels. These channels are involved in pain signalling and other processes, and apparently can couple to intracellular pathways independent of ion flow. Here the authors measure the movements of the unstructured intracellular parts of ASIC using fluorescence spectroscopy coupled to functional 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, #2, and #3 agreed to share their names with the authors.)

Reviewed by eLife

Fibrinogen αC-subregions critically contribute blood clot fibre growth, mechanical stability, and resistance to fibrinolysis

1. Helen R McPherson
2. Cedric Duval
3. Stephen R Baker
4. Matthew S Hindle
5. Lih T Cheah
6. Nathan L Asquith
7. Marco M Domingues
8. Victoria C Ridger
9. Simon DA Connell
10. Khalid M Naseem
11. Helen Philippou
12. Ramzi A Ajjan
13. Robert AS Ariëns

• Curated by eLife

  Evaluation Summary:

  This paper is of interest to a broad audience in the blood coagulation and fibrinolysis field. Previously undescribed roles in a range of blood clot properties are attributed to a region of the clotting protein fibrinogen, using state-of-the-art methodology. The data support the main conclusions of the paper, open new avenues of investigation for understanding clot properties, and have clinical implications.

  (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

Use of hiPSC-Derived Cardiomyocytes to Rule Out Proarrhythmic Effects of Drugs: The Case of Hydroxychloroquine in COVID-19

1. Luca Sala
2. Vladislav Leonov
3. Manuela Mura
4. Federica Giannetti
5. Aleksandr Khudiakov
6. Alessandra Moretti
7. Lia Crotti
8. Massimiliano Gnecchi
9. Peter J. Schwartz

Reviewed by ScreenIT

Modulation of fracture healing by the transient accumulation of senescent cells

1. Dominik Saul
2. David G Monroe
3. Jennifer L Rowsey
4. Robyn Laura Kosinsky
5. Stephanie J Vos
6. Madison L Doolittle
7. Joshua N Farr
8. Sundeep Khosla

• Curated by eLife

  Evaluation Summary:

  This is a well conducted study that examines the potential role of senescent cells in fracture healing. Furthermore, the authors have used senolytic agents to examine if targeting cellular senescence will have a significant impact on fracture healing phenotype. The manuscript is succinctly written, and the methods and results are well described. These data provide the first demonstration for a potential role for cellular senescence in regulating fracture healing. The authors’ conclusions are largely supported by the experimental 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. Reviewers #1, #2, and #3 agreed to share their names with the authors.)

Reviewed by eLife

P. falciparum K13 mutations present varying degrees of artemisinin resistance and reduced fitness in African parasites

1. Barbara H. Stokes
2. Kelly Rubiano
3. Satish K. Dhingra
4. Sachel Mok
5. Judith Straimer
6. Nina F. Gnädig
7. Jade R. Bath
8. Ioanna Deni
9. Kurt E. Ward
10. Josefine Striepen
11. Tomas Yeo
12. Leila S. Ross
13. Eric Legrand
14. Frédéric Ariey
15. Clark H. Cunningham
16. Issa M. Souleymane
17. Adama Gansané
18. Romaric Nzoumbou-Boko
19. Claudette Ndayikunda
20. Abdunoor M. Kabanywanyi
21. Aline Uwimana
22. Samuel J. Smith
23. Olimatou Kolley
24. Mathieu Ndounga
25. Marian Warsame
26. Rithea Leang
27. François Nosten
28. Timothy J.C. Anderson
29. Philip J. Rosenthal
30. Didier Ménard
31. David A. Fidock

• Curated by eLife

  Evaluation Summary:

  This study is of interest to the broad malaria research community and especially those who work on drug resistance. The authors provide a summary of their surveys of African and Southeast Asian Plasmodium falciparum parasites for the Kelch 13 gene, a marker of artemisinin resistance. The contribution of several K13 mutations to artemisinin resistance is investigated in different genetic backgrounds and confirms the lack of a barrier for the potential emergence of artemisinin resistance in African parasites. These findings are of prime importance in the context of public health perspective on managing the risk of resistance appearing in Africa.

  (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

Combustible and Electronic Cigarette Exposures Increase ACE2 Activity and SARS-CoV-2 Spike Binding

1. Arunava Ghosh
2. Vishruth Girish
3. Monet Lou Yuan
4. Raymond D. Coakley
5. Joe A. Wrennall
6. Neil E. Alexis
7. Erin L. Sausville
8. Anand Vasudevan
9. Alexander R. Chait
10. Jason M. Sheltzer
11. Robert Tarran

Reviewed by ScreenIT

Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya

1. Samuel Kariuki
2. Zoe A Dyson
3. Cecilia Mbae
4. Ronald Ngetich
5. Susan M Kavai
6. Celestine Wairimu
7. Stephen Anyona
8. Naomi Gitau
9. Robert Sanaya Onsare
10. Beatrice Ongandi
11. Sebastian Duchene
12. Mohamed Ali
13. John David Clemens
14. Kathryn E Holt
15. Gordon Dougan

Reviewed by eLife

The anti-immune dengue subgenomic flaviviral RNA is found in vesicles in mosquito saliva and associated with increased infectivity

1. Shih-Chia Yeh
2. Wei-Lian Tan
3. Avisha Chowdhury
4. Vanessa Chuo
5. R. Manjunatha Kini
6. Julien Pompon
7. Mariano A. Garcia-Blanco

• Curated by eLife

  Evaluation Summary:

  Mosquito saliva can enhance transmission of arboviruses. Here, authors demonstrated that the anti-immune non-coding RNA from Dengue virus, known as the subgenomic flavivirus RNA (sfRNA), is secreted into mosquito saliva within the extracellular vesicles and can facilitate infection of the acceptor human cells when delivered together with infectious virus in mosquito saliva. The study potentially expands our understanding of flavivirus transmission.

  (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

Divergent regulation of KCNQ1/E1 by targeted recruitment of protein kinase A to distinct sites on the channel complex

1. Xinle Zou
2. Sri Karthika Shanmugam
3. Scott A Kanner
4. Kevin J Sampson
5. Robert S Kass
6. Henry M Colecraft

• Curated by eLife

  eLife assessment

  This important study provides a substantial advance with a method by which a protein target resistant to therapeutic approaches can be uniquely modulated by a cellular protein kinase ferried by nanobodies to a precise molecular site of recruitment. Evidence for this major claim is compelling, but evidence for some of the minor claims seems incomplete. The work will be of broad interest to cell biologists, cardiovascular researchers, and drug developers.

Reviewed by eLife

Personalized Virus Load Curves of SARS-CoV-2 Infection

1. Thomas Hillen
2. Carlos Contreras
3. Jay M. Newby

Reviewed by ScreenIT