Metabolic pathways that regulate T-cell function show promise as therapeutic targets in diverse diseases. Here, we show that at rest cultured human effector memory and central memory CD4+ T-cells have elevated levels of glycolysis and oxidative phosphorylation (OXPHOS), in comparison to naïve T-cells. Despite having low resting metabolic rates, naive T-cells respond to TCR stimulation with robust and rapid increases in glycolysis and OXPHOS. This early metabolic switch requires Akt activity to support increased rates of glycolysis and STAT5 activity for amino acid biosynthesis and TCA cycle anaplerosis. Importantly, both STAT5 inhibition and disruption of TCA cycle anaplerosis are associated with reduced IL-2 production, demonstrating the functional importance of this early metabolic program. Our results define STAT5 as a key node in modulating the early metabolic program following activation in naive CD4+ T-cells and in turn provide greater understanding of how cellular metabolism shapes T-cell responses.
The flipped classroom is a relatively new active learning pedagogical intervention, gaining popularity as a blended learning methodology. The flipped classroom comprises two distinct parts, directed learning carried out at the student's own pace away from the classroom and an interactive, class-based activity encouraging problem-solving and experiential learning. This research presents a 1-year study to measure student performance and perception toward a flipped classroom approach to teaching core biochemical calculations to first-year undergraduate biochemistry and genetics students. A post-task questionnaire showed an overall positive student perception with an associated significant improvement in the end of module summative assessment. These results suggest that this teaching approach offers some advantages over more traditional teaching pedagogies. K E Y W O R D S biochemistry and genetics, flipped classroom, molar calculations, undergraduate teaching.
Birth represents a relatively dramatic transition from an environment with a low microbial burden to one abundant in commensal and potentially pathogenic challenges that the neonatal immune system must be able to respond to. Immune responses in preterm and term neonates differ from those of adults, generally being characterized as diminished, tolerant or Th skewed although we must be mindful that these are highly evolved, stage of life appropriate responses.Efforts to clarify the phenotypes and mechanisms prevalent at this time are ongoing so that we can better understand the significance of differences at this stage of development for long-term health.The need to understand how the neonatal immune response differs to that of adults is driven by the mortality and morbidity associated with infection and sepsis in newborns and infants and the need for protective vaccine responses that can mitigate these.
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