1. Biochemistry and Chemical Biology
  2. Cell Biology
Download icon

Science Forum: The Brazilian Reproducibility Initiative

  1. Olavo B Amaral  Is a corresponding author
  2. Kleber Neves
  3. Ana P Wasilewska-Sampaio
  4. Clarissa FD Carneiro
  1. Federal University of Rio de Janeiro, Brazil
Feature Article
  • Cited 6
  • Views 2,054
  • Annotations
Cite this article as: eLife 2019;8:e41602 doi: 10.7554/eLife.41602

Abstract

Most efforts to estimate the reproducibility of published findings have focused on specific areas of research, even though science is usually assessed and funded on a regional or national basis. Here we describe a project to assess the reproducibility of findings in biomedical science published by researchers based in Brazil. The Brazilian Reproducibility Initiative is a systematic, multi-center effort to repeat between 60 and 100 experiments: the project will focus on a set of common laboratory methods, repeating each experiment in three different laboratories. The results, due in 2021, will allow us to estimate the level of reproducibility of biomedical science in Brazil, and to investigate what the published literature can tell us about the reproducibility of research in a given area.

Article and author information

Author details

  1. Olavo B Amaral

    Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    For correspondence
    olavo@bioqmed.ufrj.br
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4299-8978
  2. Kleber Neves

    Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  3. Ana P Wasilewska-Sampaio

    Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  4. Clarissa FD Carneiro

    Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8127-0034

Funding

Instituto Serrapilheira

  • Olavo B Amaral

CNPq

  • Clarissa FD Carneiro

The project's funder (Instituto Serrapilheira) made suggestions on the study design, but had no role in data collection and interpretation, or in the decision to submit the work for publication. K. N. and A.P.W.S. are supported by post-doctoral scholarships within this project. C.F.D.C. is supported by a PhD scholarship from CNPq.

Reviewing Editor

  1. Peter A Rodgers, eLife, United Kingdom

Publication history

  1. Received: September 3, 2018
  2. Accepted: January 25, 2019
  3. Accepted Manuscript published: February 5, 2019 (version 1)
  4. Version of Record published: February 13, 2019 (version 2)

Copyright

© 2019, Amaral et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,054
    Page views
  • 182
    Downloads
  • 6
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Biochemistry and Chemical Biology
    Johannes Rudolph et al.
    Research Article

    Poly(ADP-ribose) polymerase 1 (PARP1) is an important player in the response to DNA damage. Recently, histone PARylation factor (HPF1) was shown to be a critical modulator of the activity of PARP1 by facilitating PARylation of histones and redirecting the target amino acid specificity from acidic to serine residues. Here we investigate the mechanism and specific consequences of HPF1-mediated PARylation using nucleosomes as both activators and substrates for PARP1. HPF1 provides that catalytic base Glu284 to substantially redirect PARylation by PARP1 such that the histones in nucleosomes become the primary recipients of PAR chains. Surprisingly, HPF1 partitions most of the reaction product to free ADPR, resulting in much shorter PAR chains compared to reactions in the absence of HPF1. This HPF1-mediated switch from polymerase to hydrolase has important implications for the PARP1-mediated response to DNA damage and raises interesting new questions about the role of intracellular ADPR and depletion of NAD+.

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics
    Palur V Raghuvamsi et al.
    Research Article Updated

    The spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface angiotensin-converting enzyme 2 (ACE2) receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, using amide hydrogen–deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped the S:ACE2 interaction interface and uncovered long-range allosteric propagation of ACE2 binding to sites necessary for host-mediated proteolysis of S protein, critical for viral host entry. Unexpectedly, ACE2 binding enhances dynamics at a distal S1/S2 cleavage site and flanking protease docking site ~27 Å away while dampening dynamics of the stalk hinge (central helix and heptad repeat [HR]) regions ~130 Å away. This highlights that the stalk and proteolysis sites of the S protein are dynamic hotspots in the prefusion state. Our findings provide a dynamics map of the S:ACE2 interface in solution and also offer mechanistic insights into how ACE2 binding is allosterically coupled to distal proteolytic processing sites and viral–host membrane fusion. Thus, protease docking sites flanking the S1/S2 cleavage site represent alternate allosteric hotspot targets for potential therapeutic development.