Unique expression of genes influencing transendothelial leukocyte migration in HIV-1 resistant women in the pumwani sex worker cohort
Bibliographic record
Abstract
OBJECTIVE: The Pumwani Sexworker Cohort in Nairobi, Kenya has enrolled >2100 women from 1985 to 2002. A small subset of women enrolled during this period remain HIV uninfected despite high-risk sex work exposures. This study investigated the expression of genes involved in leukocyte movement and migration and their role in HIV resistance. METHODS: Whole blood was collected from 75 HIV uninfected women: 38 HIV resistant women (average of 15.39 negative years) and 37 susceptible new enrollees (average of 1.027 negative years). The mRNA expression of 84 genes was analyzed using a custom RT2 Profiler PCR-array and compared between HIV resistant women and HIV negative susceptible controls. The function and influence of genes with mRNA significantly differentially expressed were analyzed using Ingenuity Pathway Analysis (QIAGEN) and Pathway Studio (Elsevier). RESULTS: Eighteen genes were significantly up-expressed in HIV resistant women. Among them, 16 genes are involved in the leukocyte movement and migration (p < 0.00001). Among them, 4 genes (CTNNB1, ITGB1, PIK3CA and PTPN11) are involved in transendothelial leukocyte migration signaling (p < 0.00001), 8 genes (CTNNB1, DPP4, ITGB1, PIK3CA, PTPN11, TICAM1, TIMP1, VCAN) are involved in cellular infiltration by leukocytes (p < 0.00001), and 6 genes (CTNNB1, ITGB1, MAP3K4, PIK3CA, PTPN11, TIMP1) are involved in the Leukocyte Extravasation Signaling (p < 0.00001). DISCUSSION/CONCLUSIONS: We propose that the HIV resistant women of the PSC may exhibit a unique leukocyte migratory response in dealing with pathogen infection. The potential mechanisms could contribute to the unique leukocyte migratory response: modifications to the PI3K/AKT signaling, extracellular matrix remodeling, integrin structure and function, and activation of T-cell receptors.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".