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Record W3087927086 · doi:10.1016/j.celrep.2020.108170

Bisphosphoglycerate Mutase Deficiency Protects against Cerebral Malaria and Severe Malaria-Induced Anemia

2020· article· en· W3087927086 on OpenAlexafffund
Guoyue Xu, Rebekah van Bruggen, Christian O. Gualtieri, Neda Moradin, Adrien Fois, Diane Vallerand, Mariana De Sa Tavares Russo, Angelia V. Bassenden, Wenyun Lu, Mifong Tam, Sylvie Lesage, Hélène Girouard, Daina Avizonis, Geneviève Deblois, Josef T. Prchal, Mary M. Stevenson, Albert M. Berghuis, Tom W. Muir, Joshua D. Rabinowitz, Silvia M. Vidal, Nassima Fodil, Philippe Gros

Bibliographic record

VenueCell Reports · 2020
Typearticle
Languageen
FieldMedicine
TopicHemoglobinopathies and Related Disorders
Canadian institutionsInstitute for Research in Immunology and CancerOccupational Cancer Research CentreMcGill UniversityUniversité de MontréalHôpital Maisonneuve-RosemontMcGill University Health Centre
FundersNational Cancer InstituteFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchUniversity of TorontoTerry Fox FoundationFondation du cancer du sein du QuébecCanadian Institute for Advanced ResearchRoyal Bank of CanadaMcGill University
KeywordsMalariaAnemiaCerebral MalariaImmunologyMedicinePlasmodium falciparumBiologyVirologyInternal medicine

Abstract

fetched live from OpenAlex

The replication cycle and pathogenesis of the Plasmodium malarial parasite involves rapid expansion in red blood cells (RBCs), and variants of certain RBC-specific proteins protect against malaria in humans. In RBCs, bisphosphoglycerate mutase (BPGM) acts as a key allosteric regulator of hemoglobin/oxyhemoglobin. We demonstrate here that a loss-of-function mutation in the murine Bpgm ( Bpgm L166P ) gene confers protection against both Plasmodium -induced cerebral malaria and blood-stage malaria. The malaria protection seen in Bpgm L166P mutant mice is associated with reduced blood parasitemia levels, milder clinical symptoms, and increased survival. The protective effect of Bpgm L166P involves a dual mechanism that enhances the host's stress erythroid response to Plasmodium -driven RBC loss and simultaneously alters the intracellular milieu of the RBCs, including increased oxyhemoglobin and reduced energy metabolism, reducing Plasmodium maturation, and replication. Overall, our study highlights the importance of BPGM as a regulator of hemoglobin/oxyhemoglobin in malaria pathogenesis and suggests a new potential malaria therapeutic target.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.214
Teacher spread0.203 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations12
Published2020
Admission routes2
Has abstractyes

Explore more

Same venueCell ReportsSame topicHemoglobinopathies and Related DisordersFrench-language works237,207