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 4
  • Views 1,972
  • 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

  • 1,972
    Page views
  • 178
    Downloads
  • 4
    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
    Eric M Jones et al.
    Tools and Resources Updated

    The >800 human G protein–coupled receptors (GPCRs) are responsible for transducing diverse chemical stimuli to alter cell state- and are the largest class of drug targets. Their myriad structural conformations and various modes of signaling make it challenging to understand their structure and function. Here, we developed a platform to characterize large libraries of GPCR variants in human cell lines with a barcoded transcriptional reporter of G protein signal transduction. We tested 7800 of 7828 possible single amino acid substitutions to the beta-2 adrenergic receptor (β2AR) at four concentrations of the agonist isoproterenol. We identified residues specifically important for β2AR signaling, mutations in the human population that are potentially loss of function, and residues that modulate basal activity. Using unsupervised learning, we identify residues critical for signaling, including all major structural motifs and molecular interfaces. We also find a previously uncharacterized structural latch spanning the first two extracellular loops that is highly conserved across Class A GPCRs and is conformationally rigid in both the inactive and active states of the receptor. More broadly, by linking deep mutational scanning with engineered transcriptional reporters, we establish a generalizable method for exploring pharmacogenomics, structure and function across broad classes of drug receptors.

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics
    Xiaowei Hou et al.
    Research Advance

    The calcium release-activated calcium channel Orai regulates Ca2+ entry into non-excitable cells and is required for proper immune function. While the channel typically opens following Ca2+ release from the endoplasmic reticulum, certain pathologic mutations render the channel constitutively open. Previously, using one such mutation (H206A), we obtained low (6.7 Å) resolution X-ray structural information on Drosophila melanogaster Orai in an open conformation (Hou, Burstein, & Long, 2018). Here, we present a structure of this open conformation at 3.3 Å resolution using fiducial-assisted cryo-EM. The improved structure reveals the conformations of amino acids in the open pore, which dilates by outward movements of subunits. A ring of phenylalanine residues repositions to expose previously shielded glycine residues to the pore without significant rotational movement of the associated helices. Together with other hydrophobic amino acids, the phenylalanines act as the channel's gate. Structured M1-M2 turrets, not evident previously, form the channel's extracellular entrance.