Evidence map›Paper›PMID 26483558›Full record

ArticleThe Journal of cell biology2015

Molecular control of irreversible bistability during trypanosome developmental commitment.

Maria Rosa Domingo-Sananes, Balazs Szöőr, Michael A J Ferguson, Michael D Urbaniak, Keith R Matthews

Abstract read
In one paragraph

Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
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

25 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. NNature · 2022
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
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  14. Dissipative structures in biological systems: bistability, oscillations, spatial patterns and waves.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2018
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

5 authors.

Maria Rosa Domingo-SananesCentre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, Scotland, UK.
Balazs SzöőrCentre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, Scotland, UK.
Michael A J FergusonDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Michael D UrbaniakDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YG, England, UK m.urbaniak@lancaster.ac.uk keith.matthews@ed.ac.uk.
Keith R MatthewsCentre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, Scotland, UK m.urbaniak@lancaster.ac.uk keith.matthews@ed.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/M009556/1Wellcome Trust 095831Wellcome Trust 097945Wellcome Trust 101842Wellcome Trust 103740Wellcome Trust 103740/Z/14/Z
6 · The paper itself

Abstract

The life cycle of Trypanosoma brucei involves developmental transitions that allow survival, proliferation, and transmission of these parasites. One of these, the differentiation of growth-arrested stumpy forms in the mammalian blood into insect-stage procyclic forms, can be induced synchronously in vitro with cis-aconitate. Here, we show that this transition is an irreversible bistable switch, and we map the point of commitment to differentiation after exposure to cis-aconitate. This irreversibility implies that positive feedback mechanisms operate to allow commitment (i.e., the establishment of "memory" of exposure to the differentiation signal). Using the reversible translational inhibitor cycloheximide, we show that this signal memory requires new protein synthesis. We further performed stable isotope labeling by amino acids in cell culture to analyze synchronized parasite populations, establishing the protein and phosphorylation profile of parasites pre- and postcommitment, thereby defining the "commitment proteome." Functional interrogation of this data set identified Nek-related kinase as the first-discovered protein kinase controlling the initiation of differentiation to procyclic forms.

Indexed as

Aconitic AcidCell Cycle ProteinsCell DifferentiationCycloheximideGene Expression Regulation, DevelopmentalIsotope LabelingLife Cycle StagesNIMA-Related Kinase 1PhosphorylationProtein BiosynthesisProtein Serine-Threonine KinasesProteomeProtozoan ProteinsSignal TransductionStaining and LabelingTrypanosoma brucei bruceiAconitic AcidCell Cycle ProteinsCycloheximideNIMA-Related Kinase 1Protein Serine-Threonine KinasesProteomeProtozoan Proteins

Identifiers

PMID26483558
PMCPMC4621835

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.