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Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL), a Resistance Mechanism for Two Distinct Compound Classes

Overview of attention for article published in ACS Infectious Diseases, April 2016
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1 tweeter

Citations

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37 Mendeley
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Title
Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL), a Resistance Mechanism for Two Distinct Compound Classes
Published in
ACS Infectious Diseases, April 2016
DOI 10.1021/acsinfecdis.6b00025
Pubmed ID
Authors

Pamela A. Magistrado, Victoria C. Corey, Amanda K. Lukens, Greg LaMonte, Erika Sasaki, Stephan Meister, Melanie Wree, Elizabeth Winzeler, Dyann F. Wirth

Abstract

MMV007564 is a novel antimalarial benzimidazolyl piperidine chemotype identified in cellular screens. To identify the genetic determinant of MMV007564 resistance, parasites were cultured in the presence of the compound to generate resistant lines. Whole genome sequencing revealed distinct mutations in the gene named Plasmodium falciparum cyclic amine resistance locus (pfcarl), encoding a conserved protein of unknown function. Mutations in pfcarl are strongly associated with resistance to a structurally unrelated class of compounds, the imidazolopiperazines, including KAF156, currently in clinical trials. Our data demonstrate that pfcarl mutations confer resistance to two distinct compound classes, benzimidazolyl piperidines and imidazolopiperazines. However, MMV007564 and the imidazolopiperazines, KAF156 and GNF179, have different timings of action in the asexual blood stage and different potencies against the liver and sexual blood stages. These data suggest that pfcarl is a multidrug-resistance gene rather than a common target for benzimidazolyl piperidines and imidazolopiperazines.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 37 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 30%
Student > Master 7 19%
Student > Ph. D. Student 4 11%
Other 3 8%
Professor > Associate Professor 3 8%
Other 4 11%
Unknown 5 14%
Readers by discipline Count As %
Chemistry 14 38%
Agricultural and Biological Sciences 6 16%
Immunology and Microbiology 5 14%
Biochemistry, Genetics and Molecular Biology 3 8%
Psychology 1 3%
Other 2 5%
Unknown 6 16%

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 08 April 2016.
All research outputs
#10,670,279
of 13,415,518 outputs
Outputs from ACS Infectious Diseases
#350
of 475 outputs
Outputs of similar age
#185,092
of 264,924 outputs
Outputs of similar age from ACS Infectious Diseases
#19
of 25 outputs
Altmetric has tracked 13,415,518 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 475 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 264,924 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 25 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.