Drosophila immune priming to Enterococcus faecalis relies on immune tolerance rather than resistance.

Innate immune priming increases an organism's survival of a second infection after an initial, non-lethal infection. We used Drosophila melanogaster and an insect-derived strain of Enterococcus faecalis to study transcriptional control of priming. In contrast to other pathogens, the enhanced survival in primed animals does not correlate with decreased E. faecalis load. Further analysis shows that primed organisms tolerate, rather than resist infection. Using RNA-seq of immune tissues, we found many genes were upregulated in only primed flies, suggesting a distinct transcriptional program in response to initial and secondary infections. In contrast, few genes continuously express throughout the experiment or more efficiently re-activate upon reinfection. Priming experiments in immune deficient mutants revealed Imd is largely dispensable for responding to a single infection but needed to fully prime. Together, this indicates the fly's innate immune response is plastic-differing in immune strategy, transcriptional program, and pathway use depending on infection history.

Developing an interpretation bias modification training task for alleviating loneliness in young people.

OBJECTIVE: Loneliness is common among young people and is associated with negative health outcomes. Because loneliness is associated with a bias for interpreting social situations as threatening, cognitive bias modification for interpretation (CBM-I) training is a potential early intervention tool. We developed and delivered a single session of mental imagery enhanced digital CBM-I training, assessing feasibility, acceptability, and magnitude of change in interpretational style and loneliness. METHOD: CBM-I training materials were developed using a co-creation approach with 18-25-year-olds with experience of loneliness. Another group of 18-25-year-olds with high loneliness received either online CBM-I (n = 29) or control (n = 27) training. RESULTS: CBM-I training uptake and retention rates were 88% and 92%, respectively. Participants found the training acceptable. The CBM-I group showed a reduction in social threat interpretations (d = 0.77), an increase in social benign interpretations (d = 0.84), and a decrease in loneliness (d = 0.56). The control group showed a small reduction in social threat interpretations (d = 0.21), no change in social benign interpretations (d = 0.04), and an increase in loneliness (d = 0.41). CONCLUSIONS: Interpretation biases relevant to youth loneliness may be modifiable, and CBM-I training could reduce feelings of loneliness. This informs psychological models of loneliness, and the development of CBM-I interventions targeting loneliness in young people.

The role of CaMKK2 in Golgi-associated vesicle trafficking.

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a serine/threonine-protein kinase, that is involved in maintaining various physiological and cellular processes within the cell that regulate energy homeostasis and cell growth. CaMKK2 regulates glucose metabolism by the activation of downstream kinases, AMP-activated protein kinase (AMPK) and other calcium/calmodulin-dependent protein kinases. Consequently, its deregulation has a role in multiple human metabolic diseases including obesity and cancer. Despite the importance of CaMKK2, its signalling pathways and pathological mechanisms are not completely understood. Recent work has been aimed at broadening our understanding of the biological functions of CaMKK2. These studies have uncovered new interaction partners that have led to the description of new functions that include lipogenesis and Golgi vesicle trafficking. Here, we review recent insights into the role of CaMKK2 in membrane trafficking mechanisms and discuss the functional implications in a cellular context and for disease.