Functional and genetic dissection of susceptibility to experimental «Cryptococcus neoformans» infection
Bibliographic record
Abstract
This thesis examines the functional and genetic factors that control the inbred mouse host response to Cryptococcus neoformans. The inbred mouse strains C57BL/6J and C3H/HeN were susceptible, and the inbred mouse strains CBA/J and SJL/J were resistant, to experimental cryptococcal pneumonia. This observation led to three general hypotheses: (1) early innate immune differences between inbred strains cause differential susceptibility to cryptococcal pneumonia; (2) natural variation in susceptibility among inbred strains is a complex trait under the control of specific genetic loci; and (3) allergic airway disease is a common phenotype among susceptible inbred strains. Functional characterization of the innate immune response in C57BL/6J and SJL/J mice revealed a heightened pro-inflammatory response in SJL/J as early as three hours post-infection. This polarization continued throughout the course of infection; C57BL/6J mice presented an allergic, Th2 immune response, and SJL/J mice presented a Th1 immune response. Intracellular signaling analysis in vitro revealed that the enhanced pro-inflammatory response observed in SJL/J mice was dependent on the prolonged activation of the NF-κB and phosphatidylinositol 3 kinase pathways. Next, a quantitative trait loci (QTL) analysis for cryptococcal pneumonia susceptibility in a segregating F2 population bred from the parental inbred strains C57BL/6J and CBA/J was performed. This revealed a sex-effect in the quantitative lung fungal burden that warranted a stratified QTL analysis approach. Two significant novel QTL were identified in the female F2 intercross: Cnes1 on chromosome 1, and Cnes2 on chromosome 17. Cnes3 was identified in the male F2 intercross as a unique QTL distal to Cnes2. Furthermore, a genome-wide pairwise analysis revealed significant QTL interactions in both the female and male F2 intercrosses that collectively explained 43.8 and 19.5% of the phenotypic variance in each sex, respectively. Finally, characte
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".