Molecular Biology

Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer’s model

1. Felicia Reinitz
2. Elizabeth Y Chen
3. Benedetta Nicolis di Robilant
4. Bayarsaikhan Chuluun
5. Jane Antony
6. Robert C Jones
7. Neha Gubbi
8. Karen Lee
9. William Hai Dang Ho
10. Sai Saroja Kolluru
11. Dalong Qian
12. Maddalena Adorno
13. Katja Piltti
14. Aileen Anderson
15. Michelle Monje
16. H Craig Heller
17. Stephen R Quake
18. Michael F Clarke

• Curated by eLife

  Evaluation Summary:

  This is interesting and potentially impactful work uncovering mechanisms of stem cell exhaustion and impaired self-renewal that precede inflammatory phenotypes in Alzheimer's disease. The authors describe a mechanism converging on BMP signaling that may represent an early therapeutic target. The reviewers of this manuscript were excited about the potential impact but had some concerns which, if addressed, will strengthen the conclusions reached in this work.

  (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 name with the authors.)

Reviewed by eLife

Omicron Spike Protein Has a Positive Electrostatic Surface That Promotes ACE2 Recognition and Antibody Escape

1. Hin Hark Gan
2. John Zinno
3. Fabio Piano
4. Kristin C. Gunsalus

Reviewed by ScreenIT

SARS-CoV-2 Nsp1 N-terminal and linker regions as a platform for host translational shutoff

1. Andrea Graziadei
2. Fabian Schildhauer
3. Christian Spahn
4. Matthew Kraushar
5. Juri Rappsilber

Reviewed by ScreenIT

An efficient and cost-effective method for directed mutagenesis at multiple dispersed sites—a case study with Omicron Spike DNA

1. Rita Rani
2. Kishore V L Parsa
3. Kiranam Chatti
4. Aarti Sevilimedu

Reviewed by ScreenIT

Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops

1. João C Sabino
2. Madalena R de Almeida
3. Patrícia L Abreu
4. Ana M Ferreira
5. Paulo Caldas
6. Marco M Domingues
7. Nuno C Santos
8. Claus M Azzalin
9. Ana Rita Grosso
10. Sérgio Fernandes de Almeida

• Curated by eLife

  Evaluation Summary:

  The work provides new insight into the potential role of 5hmc DNA in specific transcriptional processes. This implies that 5hmC containing DNA has specific epigenetic features beyond being a simple intermediate in interconversion between repressive 5mC and active C DNA. This work has the merit to focus the attention on a rare DNA modification, helping defining its functions, starting from in vitro evidence and extending these findings in cellular context. There are some weaknesses in the presentation of the data, the controls and the statistical analyses.

  (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

Aerosol formation during processing of potentially infectious samples on Roche immunochemistry analyzers (cobas e analyzers) and in an end-to-end laboratory workflow to model SARS-CoV-2 infection risk for laboratory operators

1. Géza V. Burghardt
2. Markus Eckl
3. Doris Huether
4. Oliver H. D. Larbolette
5. Alessia Lo Faso
6. Beatus R. Ofenloch-Haehnle
7. Marlene A. Riesch
8. Rolf A. Herb

Reviewed by ScreenIT

How concerning is a SARS-CoV-2 variant of concern? Computational predictions and the variants labeling system

1. Dana Ashoor
2. Maryam Marzouq
3. Khaled Trabelsi
4. Sadok Chlif
5. Nasser Abotalib
6. Noureddine Ben Khalaf
7. Ahmed R. Ramadan
8. M-Dahmani Fathallah

Reviewed by ScreenIT

On demand expression control of endogenous genes with DExCon, DExogron and LUXon reveals differential dynamics of Rab11 family members

1. Jakub Gemperle
2. Thomas S Harrison
3. Chloe Flett
4. Antony D Adamson
5. Patrick T Caswell

• Curated by eLife

  Evaluation Summary:

  This work reports a genome editing strategy that enables blocking and tetracycline-controlled re-expression of fluorescently-tagged proteins from endogenous loci. The authors combine this with the photoactivatable tet-on/off system, a knocksideways approach, as well as the auxin-inducible degron system to improve spatial and temporal control of gene expression. They demonstrate the applicability of the methods by studying the localization, function and protein-expression dynamics of the Rab11-family of small GTPases. Using these approaches, the authors discover subtle differences in the localization as well as expression and degradation kinetics of Rab11a/b/Rab25. The work will be of broad interest to molecular and cell biologists.

  (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

Comprehensive fitness landscape of SARS-CoV-2 Mpro reveals insights into viral resistance mechanisms

1. Julia M Flynn
2. Neha Samant
3. Gily Schneider-Nachum
4. David T Barkan
5. Nese Kurt Yilmaz
6. Celia A Schiffer
7. Stephanie A Moquin
8. Dustin Dovala
9. Daniel NA Bolon

• Curated by eLife

  Evaluation Summary:

  The main protease of SARS-CoV-2 (Mpro) is a leading target for drug design due to its conserved and indispensable role in the life cycle. This study used cutting-edge molecular and statistical methods to generate a detailed genotype-phenotype map of this protein, also called a "fitness landscape." This fitness landscape is impressive in its detail and resolution and offers new insight that can be used to potentially generate new anti-viral drugs. This study was original in conception, precise in execution, and impressive in design. In sum, this constitutes a very meaningful addition to scientific literature.

  (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 name with the authors.)

Reviewed by eLife, ScreenIT

SARS-CoV-2 Viral Genes Compromise Survival and Functions of Human Pluripotent Stem Cell-derived Cardiomyocytes via Reducing Cellular ATP Level

1. Juli Liu
2. Yucheng Zhang
3. Shiyong Wu
4. Lei Han
5. Cheng Wang
6. Sheng Liu
7. Ed Simpson
8. Ying Liu
9. Yue Wang
10. Weinian Shou
11. Yunlong Liu
12. Michael Rubart-von der Lohe
13. Jun Wan
14. Lei Yang

Reviewed by ScreenIT