Interleukin-4 downregulates transcription factor BCL6 to promote memory B cell selection in germinal centers.

Germinal center (GC)-derived memory B cells (MBCs) are critical for humoral immunity as they differentiate into protective antibody-secreting cells during re-infection. GC formation and cellular interactions within the GC have been studied in detail, yet the exact signals that allow for the selection and exit of MBCs are not understood. Here, we showed that IL-4 cytokine signaling in GC B cells directly downregulated the transcription factor BCL6 via negative autoregulation to release cells from the GC program and to promote MBC formation.

Transition-Metal-Free Continuous-Flow Synthesis of 2,5-Diaryl Furans: Access to Medicinal Building Blocks and Optoelectronic Materials.

The direct transformation of 1,3-dienes into valuable 2,5-diarylfurans using transition-metal-free conditions is presented. By employing a simple oxidation─dehydration sequence on readily accessible 1,3-dienes, important 2,5-diarylfuran building blocks frequently used in medicinal and material chemistry are prepared. The oxidation step is realized using singlet oxygen, and the intermediate endoperoxide is dehydrated under metal-free conditions and at ambient temperature using the Appel reagent.

Early T-bet promotes LFA1 upregulation required for CD8+ effector and memory T cell development.

The T-box transcription factor T-bet is regarded as a "master regulator" of CD4+ Th1 differentiation and IFN-γ production. However, in multiple models of infection, T-bet appears less critical for CD8+ T cell expansion and effector function. Here, we show that following vaccination with a replication-deficient strain of Toxoplasma gondii, CD8+ T cell expression of T-bet is required for optimal expansion of parasite-specific effector CD8+ T cells.

The experiences and perceptions of wellbeing provision among English ambulance services staff: a multi-method qualitative study.

Background: NHS ambulance service staff are at risk of poor physical and mental wellbeing because of the likelihood of encountering stressful and traumatic incidents. While reducing sickness absence and improving wellbeing support to ambulance staff is a key NHS priority, few studies have empirically documented a national picture to inform policy and service re-design. The study aimed to understand how ambulance service trusts in England deal with staff health and wellbeing, as well as how the staff perceive and use wellbeing services.

cDC1 coordinate innate and adaptive responses in the omentum required for T cell priming and memory.

In the peritoneal cavity, the omentum contains fat-associated lymphoid clusters (FALCs) whose role in response to infection is poorly understood. After intraperitoneal immunization with , conventional type 1 dendritic cells (cDC1s) were critical to induce innate sources of IFN-γ and cellular changes in the FALCs. Unexpectedly, infected peritoneal macrophages that migrated into the FALCs primed CD8 T cells.