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Record W7049252249

NOD2 and Mycobacteria

2010· dissertation· en· W7049252249 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueeScholarship@McGill (McGill) · 2010
Typedissertation
Languageen
FieldEngineering
TopicPhotocathodes and Microchannel Plates
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchMcGill University
KeywordsNOD2Innate immune systemMycobacterium tuberculosisTuberculosisPattern recognition receptorImmunityPeptidoglycanAcquired immune system
DOInot available

Abstract

fetched live from OpenAlex

The genus Mycobacterium comprises a variety of highly successful intracellular pathogens. Mycobacterium tuberculosis is the causative agent of tuberculosis (TB) in humans and currently infects one third of the world's population. Mycobacterium avium ssp. paratuberculosis is the established cause of Johne's disease in ruminants and is epidemiologically associated with Crohn's disease (CD) in humans. Both TB and CD are complex genetic diseases for which immunological pathways associated with disease susceptibility or resistance have been identified based on human genetic studies. Common polymorphisms in NOD2 have recently been described to predispose to CD. NOD2 encodes a receptor of the Nod-like receptor (NLR) family involved in mediating innate immunity upon recognition of fragments of bacterial peptidoglycan (PGN), a structural component of most bacterial cell wall. CD-associated NOD2 polymorphisms were shown to abrogate this response. While recent studies have uncovered an important role of NOD2 for the recognition of mycobacterial species, the consequences and significance of this recognition remain obscure. The first part of the work presented in this thesis investigates the consequences of NOD2-mediated recognition on innate responses, adaptive immunity and resistance to mycobacterial infection. Using Nod2-deficient mice as a model to study CD-associated NOD2 mutations in humans, we show that the NOD2 pathway is critical for both innate and acquired anti-mycobacterial immunity. Impaired mycobacterial recognition at early time points following infection altered the immunopathology in the lungs and resulted in decreased survival of Nod2-deficient mice when virulent M. tuberculosis was given by aerosol. The second part of this thesis focuses on the biochemical basis of mycobacterial recognition by NOD2. The bacterial N-acetylmuramic acid hydroxylase (NamH) enzyme introduces a specific modification in PGN. We correlated the presence of this enzyme in mycobacteri

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.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.209
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0000.000

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 head0.008
GPT teacher head0.207
Teacher spread0.199 · 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