Evidence map›Paper›PMID 28830560›Full record

ArticleJournal of negative results in biomedicine2017

In vitro aggregating β-lactamase-polyQ chimeras do not induce toxic effects in an in vivo Caenorhabditis elegans model.

Roel Van Assche, Charline Borghgraef, Jonathan Vaneyck, Mireille Dumoulin, Liliane Schoofs, Liesbet Temmerman

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of negative results in biomedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 59% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Roel Van AsscheAnimal Physiology and Neurobiology, Department of Biology, KU Leuven (University of Leuven), Zoological Institute, Naamsestraat 59, 3000, Leuven, Belgium.
Charline BorghgraefAnimal Physiology and Neurobiology, Department of Biology, KU Leuven (University of Leuven), Zoological Institute, Naamsestraat 59, 3000, Leuven, Belgium.
Jonathan VaneyckEnzymology and Protein Folding, Center for Protein Engineering, InBioS, Institute of Chemistry, University of Liège, Sart-Tilman, 4000, Liège, Belgium.
Mireille DumoulinEnzymology and Protein Folding, Center for Protein Engineering, InBioS, Institute of Chemistry, University of Liège, Sart-Tilman, 4000, Liège, Belgium.
Liliane SchoofsAnimal Physiology and Neurobiology, Department of Biology, KU Leuven (University of Leuven), Zoological Institute, Naamsestraat 59, 3000, Leuven, Belgium.
Liesbet TemmermanAnimal Physiology and Neurobiology, Department of Biology, KU Leuven (University of Leuven), Zoological Institute, Naamsestraat 59, 3000, Leuven, Belgium. liesbet.temmerman@kuleuven.be.
KU Leuven · BEUniversity of Liège · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA series of human diseases are caused by the misfolding and aggregation of specific proteins or peptides into amyloid fibrils; nine of these diseases, referred to as polyglutamine diseases, are associated with proteins carrying an expanded polyglutamine (polyQ) region. While the presence of this latter is thought to be the determinant factor for the development of polyQ diseases, the non-polyQ regions of the host proteins are thought to play a significant modulating role.

methodIn order to better understand the role of non-polyQ regions, the toxic effects of model proteins bearing different polyQ regions (containing up to 79 residues) embedded at two distinct locations within the β-lactamase (BlaP) host enzyme were evaluated in Caenorhabditis elegans. This small organism can be advantageous for the validation of in vitro findings, as it provides a multicellular context yet avoids the typical complexity of common studies relying on vertebrate models. Several phenotypic assays were performed in order to screen for potential toxic effects of the different BlaP-polyQ proteins.

resultsDespite the significant in vitro aggregation of BlaP-polyQ proteins with long polyQ regions, none of the BlaP-polyQ chimeras aggregated in the generated transgenic in vivo models.

conclusionThe absence of a toxic effect of the expression of BlaP-polyQ chimeras may find its cause in biochemical mechanisms present in vivo to cope with protein aggregation (e.g. presence of chaperones) or in C. elegans' limitations such as its short lifespan. It is plausible that the aggregation propensities of the different BlaP chimeras containing embedded polyQ sequences are too low in this in vivo environment to permit their aggregation. These experiments emphasize the need for several comparative and in vivo verification studies of biologically relevant in vitro findings, which reveal both the strengths and limitations of widely used model systems.

Indexed as

Models, AnimalAnimalsAnimals, Genetically Modifiedbeta-LactamasesCaenorhabditis elegansChimeraPeptidesProtein AggregatesProtein Structure, Secondarybeta-LactamasesPeptidespolyglutamineProtein AggregatesCaenorhabditis elegansIn vivo protein aggregationModel polyglutamine proteinsNon-polyQ regionspolyQβ-lactamase BlaP

Identifiers

PMID28830560
PMCPMC5568214
OpenAlexW2522243733

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.