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An external sensing system in Plasmodium falciparum-infected erythrocytes

Overview of attention for article published in Malaria Journal, February 2016
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An external sensing system in Plasmodium falciparum-infected erythrocytes
Published in
Malaria Journal, February 2016
DOI 10.1186/s12936-016-1144-6
Pubmed ID

Yang Wu, Laura N. Cruz, Tadge Szestak, Gavin Laing, Gemma R. Molyneux, Celia R. S. Garcia, Alister G. Craig


A number of experiments have previously indicated that Plasmodium falciparum-infected erythrocytes (pRBC) were able to sense host environment. The basis of this ability to detect external cues is not known but in screening signalling molecules from pRBC using commercial antibodies, a 34 kDa phosphorylated molecule that possesses such ability was identified. The pRBC were exposed to different culture conditions and proteins were extracted for 1D or 2D gel electrophoresis followed by Western blot. The localization of 34 kDa protein was examined by biochemical fractionation followed by Western blot. High-resolution mass spectrometric analysis of immune precipitants was used to identify this protein and real-time quantitative reverse transcriptase polymerase chain reaction was used for detecting mRNA expression level. The 34 kDa protein was called PfAB4 has immediate responses (dephosphorylation and rapid turnover) to host environmental stimuli such as serum depletion, osmolality change and cytokine addition. PfAB4 is expressed constitutively throughout the erythrocytic lifecycle with dominant expression in trophozoites 30 h post-infection. Tumour necrosis factor (TNF) treatment induced a transient detectable dephosphorylation of PfAB4 in the ItG strain (2 min after addition) and the level of expression and phosphorylation returned to normal within 1-2 h. PfAB4 localized dominantly in pRBC cytoplasm, with a transient shift to the nucleus under TNF stimulation as shown by biochemical fractionation. High-resolution mass spectrometric analysis of immune precipitants of AB4 antibodies revealed a 34 kDa PfAB4 component as a mixture of proliferating cellular nuclear antigen-1 (PCNA1) and exported protein-2 (EXP2), along with a small number of other inconsistently identified peptides. Different parasite strains have different PfAB4 expression levels, but no significant association between mRNA and PfAB4 levels was seen, indicating that the differences may be at the post-transcriptional, presumably phosphorylation, level. A triple serine phosphorylated PCNA1 peptide was identified from the PfAB4 high expression strain only, providing further evidence that the identity of PfAB4 is PCNA1 in P. falciparum. A protein element in the human malaria parasite that responds to external cues, including the pro-inflammatory cytokine TNF have been discovered. Treatment results in a transient change in phosphorylation status of the response element, which also migrates from the parasite cytoplasm to the nucleus. The response element has been identified as PfPCNA1. This sensing response could be regulated by a parasite checkpoint system and be analogous to bacterial two-component signal transduction systems.

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Mendeley readers

The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 2%
Ghana 1 2%
Unknown 41 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 23%
Student > Ph. D. Student 9 21%
Student > Bachelor 8 19%
Student > Master 6 14%
Other 2 5%
Other 3 7%
Unknown 5 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 16 37%
Biochemistry, Genetics and Molecular Biology 12 28%
Medicine and Dentistry 5 12%
Chemistry 2 5%
Computer Science 1 2%
Other 2 5%
Unknown 5 12%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 February 2016.
All research outputs
of 21,005,902 outputs
Outputs from Malaria Journal
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Outputs of similar age
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Outputs of similar age from Malaria Journal
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Altmetric has tracked 21,005,902 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,288 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.6. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
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We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them