TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Various pathways involved in the pathogenesis of sJIA have been identified through gene expression profiling in peripheral blood mononuclear cells (PBMC), but not in neutrophils. Since neutrophils are important in tissue damage during inflammation, and are elevated as part of the acute phase response, we hypothesised that neutrophil pathways could also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab.', 'We studied the transcriptomes of peripheral blood mononuclear cells (PBMC) and neutrophils from eight paired samples obtained from 4 sJIA patients taken before and after treatment, selected on the basis that they achieved ACR90 responses within 12 weeks of therapy initiation with tocilizumab. RNA was extracted and gene expression profiling was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. A longitudinal analysis using paired t-test (p<0.05 and FC1.5) was applied to identify differentially expressed genes (DEGs) between the two time points followed by ingenuity pathway analysis. Gene Set Enrichment Analysis (GSEA) and quantitative real-time PCR were then performed to verify the microarray results.', 'Gene ontology analysis in neutrophils revealed that response to tocilizumab significantly altered genes regulating mitochondrial dysfunction and oxidative stress (p=4.6E-05). This was independently verified with GSEA, by identifying a set of oxidative genes whose expression correlated with response to tocilizumab. In PBMC, treatment of sJIA with tocilizumab appeared to affect genes in Oncostatin M signalling and B cell pathways.\Question: Are mitochondrial and oxidative stress genes differentially expressed in neutrophils of sJIA patients treated with tocilizumab : a pilot microarray study?

SOLUTION: For the first time we demonstrate that neutrophils from sJIA patients responding to tocilizumab showed significantly different changes in gene expression. These data could highlight the importance of mitochondrial genes that modulate oxidative stress in the pathogenesis of sJIA.

PROBLEM: Context: Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer.', 'Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer.\Question: Do allogeneic lymphocytes persist and traffic in feral MHC-matched mauritian cynomolgus macaques?

SOLUTION: MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naive animals may define the immune mechanisms responsible for protection and guide future vaccine development.

PROBLEM: Context: Experimental animal studies provided evidence for a synergistic effect of immunological and psychological stressors on subsequent sickness behaviours. Up to now, little corroborating evidence for such synergy exists for humans, in whom it may provide a mechanism leading to the expression of functional somatic symptoms. The aim of the present study was to determine an interaction between stress(-vulnerability) and an immunological activation on experimental pain sensitivity, i.e., pressure pain threshold and tolerance in healthy humans.', 'In healthy female participants (n=25, mean age 22.3 years), negative affectivity (NA) and experienced stress were assessed by questionnaire before receiving a Salmonella typhi vaccine or saline control in a randomized blinded cross-over design. Pressure pain threshold was assessed at the lower back and calves and pain tolerance was assessed at the thumbnail, before and six hours after each injection.', 'Vaccination induced leukocytosis (+100%) and increased serum IL-6 (+670%). NA predicted decreased pain tolerance after vaccination (=-.57, p=.007), but not after placebo (=.25, p=.26). Post-hoc analyses also demonstrated an association with administration order.\Question: Does negative affectivity predict decreased pain tolerance during low-grade inflammation in healthy women?

SOLUTION:
NA moderated the effects of inflammation on pain tolerance. This finding is consistent with a synergistic model whereby inflammation may lower the threshold for pain reporting in individuals with increased vulnerability for somatic symptom reporting.