Memory B cells (MBCs) have enhanced capabilities to differentiate to plasma cells and generate a rapid burst of Abs upon secondary stimulation. To determine if MBCs harbor an epigenetic landscape that contributes to increased differentiation potential, we derived the chromatin accessibility and transcriptomes of influenza-specific IgM and IgG MBCs compared with naive cells. MBCs possessed an accessible chromatin architecture surrounding plasma cell-specific genes, as well as altered expression of transcription factors and genes encoding cell cycle, chemotaxis, and signal transduction processes. Intriguingly, this MBC signature was conserved between humans and mice. selleck compound MBCs of both species possessed a heightened heme signature compared with naive cells. Differentiation in the presence of hemin enhanced oxidative phosphorylation metabolism and MBC differentiation into Ab-secreting plasma cells. Thus, these data define conserved MBC transcriptional and epigenetic signatures that include a central role for heme and multiple other pathways in augmenting MBC reactivation potential.Human primary monocytes are composed of a minor, more mature CD16+(CD14low/neg) population and a major CD16neg(CD14+) subset. The specific functions of CD16+ versus CD16neg monocytes in steady state or inflammation remain poorly understood. In previous work, we found that IL-12 is selectively produced by the CD16+ subset in response to the protozoan pathogen, Toxoplasma gondii In this study, we demonstrated that this differential responsiveness correlates with the presence of an IFN-induced transcriptional signature in CD16+ monocytes already at baseline. Consistent with this observation, we found that in vitro IFN-γ priming overcomes the defect in the IL-12 response of the CD16neg subset. In contrast, pretreatment with IFN-γ had only a minor effect on IL-12p40 secretion by the CD16+ population. Moreover, inhibition of the mTOR pathway also selectively increased the IL-12 response in CD16neg but not in CD16+ monocytes. We further demonstrate that in contrast to IFN-γ, IFN-α fails to promote IL-12 production by the CD16neg subset and blocks the effect of IFN-γ priming. Based on these observations, we propose that the acquisition of IL-12 responsiveness by peripheral blood monocyte subsets depends on extrinsic signals experienced during their developmental progression in vivo. This process can be overridden during inflammation by the opposing regulatory effects of type I and II IFN as well as the mTOR inhibition. Phyllodes tumours (PTs) categorised as benign, borderline and malignant, account for 1% of all breast tumours. Histological assessment does not always predict tumour behaviour, hindering determination of the clinical course and management.Epithelial-mesenchymal transition (EMT) is an important process during embryogenesis. Dysregulation of EMT causes loss of cell polarity, decreased intercellular adhesion, increased motility and invasiveness, promoting tumour progression. Similarly, cancer stem cells (CSCs) promote tumour growth, resistance and recurrence. The aim of this study is to evaluate expression of CSC markers; enhancer of zeste homolog 2 (EZH2), CD24 and CD44 and EMT associated proteins; ezrin (EZR) and high-mobility group AT-hook 2 (HMGA2) in PTs. Uing tissue microarray sections, immunohistochemistry was performed on 360 PTs. Epithelial and stromal expressions of EZH2, EZR, HMGA2, CD24 and CD44 were evaluated to assess their impact on disease progression and behaviour in correlation with clinicopathological parameters. Stromal expression of EZH2, EZR and HMGA2 was observed in 73 (20.3%), 53 (14.7%) and 28 (7.8%) of tumours, epithelial expression in 121 (35.9%), 3 (0.8%) and 351 (97.5%) tumours, respectively. CD24 and CD44 staining was absent in both components. Expression of biomarkers correlated significantly with aggressive tumour traits such as stromal hypercellularity, atypia, mitoses and permeative tumour borders.Stromal expression of EZH2 and EZR shortened disease-free survival and overall survival; HMGA2 expression did not alter patient survival. EZH2 and EZR may thus be useful in predicting PT behaviour.Expression of biomarkers correlated significantly with aggressive tumour traits such as stromal hypercellularity, atypia, mitoses and permeative tumour borders.Stromal expression of EZH2 and EZR shortened disease-free survival and overall survival; HMGA2 expression did not alter patient survival. EZH2 and EZR may thus be useful in predicting PT behaviour. The recommended front of neck access procedure in can't intubate, can't oxygenate scenarios relies on palpation of the cricothyroid membrane (CTM), or dissection of the neck down to the larynx if CTM is impalpable. CTM palpation is particularly challenging in obese patients, most likely due to an increased distance between the skin and the CTM (CTM depth). The aims of this study were to measure the CTM depth in a representative clinical sample, and to quantify the relationship between body mass index (BMI) and CTM depth. This is a retrospective analysis of 355 clinical CT scans performed at a teaching hospital over an 8-month period. CTM depth was measured by two radiologists, and mean CTM depth calculated. Age, gender, height and weight were recorded, and BMI calculated. Linear relationships between patient characteristics and CTM depth were assessed in order to derive a predictive equation for calculating CTM depth. The variables included for this model were those with a strong association with CTM depth, that is, a p value of 0.10 or less. Mean CTM depth was 8.12 mm (IQR 6.36-11.70). There was no association between CTM depth and sex (β -0.33, 95% CI -1.33 to 0.68, p=0.53), height (cm) (β 0.01, 95% CI -0.05 to 0.06, p=0.79) or age (years) (β -0.01, 95% CI 0.10 to 0.15, p=0.62). Increasing weight (kg) (β 0.12, 95% CI 0.10 to 0.15, p<0.001) and BMI (kg/m ) (β 0.52, 95% CI 0.44 to 0.60, p<0.001) were strongly associated with CTM depth. Predicted CTM depth increased from 6.4 mm (95% CI 4.9 to 8.1) at a BMI of 20 kg/m to 16.8 (95% CI 13.7 to 20.1) at BMI 40 kg/m . CTM depth was strongly associated with BMI in a retrospective analysis of patients having clinical CT scans.CTM depth was strongly associated with BMI in a retrospective analysis of patients having clinical CT scans.