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Record W2604226451 · doi:10.1093/toxsci/kfx067

From the Cover: Tributyltin Alters the Bone Marrow Microenvironment and Suppresses B Cell Development

2017· article· en· W2604226451 on OpenAlexafffund
Amelia H. Baker, Ting Wu, Alicia M. Bolt, Louis C. Gerstenfeld, Koren K. Mann, Jennifer J. Schlezinger

Bibliographic record

VenueToxicological Sciences · 2017
Typearticle
Languageen
FieldEngineering
TopicMarine Biology and Environmental Chemistry
Canadian institutionsMcGill UniversityJewish General Hospital
FundersNational Institute of Environmental Health SciencesNatural Sciences and Engineering Research Council of Canada
KeywordsAdipogenesisStromal cellTributyltinBone marrowChemistryMesenchymal stem cellHaematopoiesisCell biologyCancer researchPharmacologyEndocrinologyInternal medicineImmunologyStem cellBiologyMedicine

Abstract

fetched live from OpenAlex

Organotins are industrial chemicals and agricultural pesticides, and they contaminate both outdoor and indoor environments. Organotins are detectable in human sera at biologically active concentrations and are immuno-and neuro-toxicants. Triphenyltin, tributyltin (TBT) and dibutyltin activate peroxisome proliferator-activated receptor γ in bone marrow multipotent mesenchymal stromal cells and promote adipogenesis. TBT also has been shown to suppress osteogenesis; osteoblasts not only support bone homeostasis but also support B lymphopoiesis. In addition, developing B cells are highly sensitive to exogenous insults. Thus, we hypothesized that bone marrow B cells may be negatively affected by TBT exposure both directly, through activation of apoptosis, and indirectly, through alterations of the bone marrow microenvironment. TBT activated apoptosis in developing B cells at environmentally relevant concentrations (as low as 80 nM) in vitro, via a mechanism that is distinct from that induced by high dose (μM) TBT and that requires p53. TBT suppressed the proliferation of hematopoietic cells in an ex vivo bone marrow model. Concurrent treatment of stromal cells and B cells or pretreatment of stromal cells with TBT induced adipogenesis in the stromal cells and reduced the progression of B cells from the early pro B (Hardy fraction B) to the pre B stage (Hardy fraction D). In vivo, TBT induced adipogenesis in bone marrow, reduced "aging-sensitive" AA4+CD19+ B cells in bone marrow, and reduced splenic B cell numbers. Immunosenescence and osteoporosis are adverse health effects of aging, we postulate that TBT exposure may mimic, and possibly intensify, these pathologies.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.394
Threshold uncertainty score0.614

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.016
GPT teacher head0.209
Teacher spread0.192 · 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 teacher head, 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

Citations29
Published2017
Admission routes2
Has abstractyes

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