Regulation of B cell fate by chronic activity of the IgE B cell receptor.

IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE+ B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE+ germinal center (GC) B cell but variably increased PC responses. We were unable to confirm reports that the IgE BCR directly promoted intrinsic apoptosis. Instead, IgE+ GC B cells exhibited poor antigen presentation and prolonged cell cycles, suggesting reduced competition for T cell help. We propose that chronic BCR activity and access to T cell help play critical roles in regulating IgE responses

Electronic cigarette use and risk perception in a Stop Smoking Service in England

Introduction: Electronic cigarette (e-cigarette) use rose substantially within the UK in recent years but currently, Stop Smoking Services in England do not prescribe them due to a lack of regulation. Previous research has examined e-cigarette use and attitudes within English Stop Smoking Services using samples of practitioners and managers; the current study recruited a sample of service users. Methods: Participants (N¼319) aged 18–60 years old were recruited from Roy Castle FagEnds, Liverpool, England (Stop Smoking Service). A cross-sectional questionnaire was completed, which recorded demographic variables, e-cigarette use alongside risk perception, and lastly, smoking behaviour i.e. smoking duration, cigarettes per day, and nicotine dependence. Results: Most participants were female (57.1%), current smokers (53.0%), and current or former e-cigarette users (51.7%). Participants who perceived e-cigarettes as less harmful than smoked tobacco were more likely to have smoked fewer cigarettes per day (p¼0.008). Furthermore, those who felt uncertain whether e-cigarettes were safer than smoked tobacco, were less likely to have tried them (p50.001). Conclusion: This study suggests that e-cigarette use is becoming common among users of Stop Smoking Services (despite e-cigarettes being unavailable from such services) and that e-cigarette risk perception is related to e-cigarette status. The results highlight the importance of providing smokers intending to quit smoking with current and accurate e-cigarette information. Findings may inform future Stop Smoking Services provision and the results demonstrate that further research is warranted

B cell receptor ligation induces IgE plasma cell elimination

The proper regulation of IgE production safeguards against allergic disease, highlighting the importance of mechanisms that restrict IgE plasma cell (PC) survival. IgE PCs have unusually high surface B cell receptor (BCR) expression, yet the functional consequences of ligating this receptor are unknown. Here, we found that BCR ligation induced BCR signaling in IgE PCs followed by their elimination. In cell culture, exposure of IgE PCs to cognate antigen or anti-BCR antibodies induced apoptosis. IgE PC depletion correlated with the affinity, avidity, amount, and duration of antigen exposure and required the BCR signalosome components Syk, BLNK, and PLCγ2. In mice with a PC-specific impairment of BCR signaling, the abundance of IgE PCs was selectively increased. Conversely, BCR ligation by injection of cognate antigen or anti-IgE depleted IgE PCs. These findings establish a mechanism for the elimination of IgE PCs through BCR ligation. This has important implications for allergen tolerance and immunotherapy as well as anti-IgE monoclonal antibody treatments

Density functional theory calculations of adsorption-induced surface stress changes

Density functional theory calculations of adsorbate-induced surface stress changes have been performed for a number of adsorbate and overlayer systems for which experimental data exists, namely: oxygen and sulphur adsorption on Ni(1 0 0); oxygen adsorption on W(1 1 0); pseudomorphic growth of Ni on Cu(1 0 0) and of Fe on W(1 1 0); oxygen adsorption on a 5 ML pseudomorphic film of Ni(1 0 0) grown on Cu(1 0 0). The theoretical calculations reproduce all the qualitative features of the experimental data, but there are some significant quantitative differences, most notably for the two atomic adsorbates on the bulk Ni(1 0 0) surface, for which the theoretical stress changes are substantially smaller than the experimental ones, a situation not obviously attributable to experimental error. For the W(1 1 0)/Fe system there is also a marked difference between experiment and theory in the coverage at which key surface stress changes occur

Scarring Effects on Tunneling in Chaotic Double-Well Potentials

The connection between scarring and tunneling in chaotic double-well potentials is studied in detail through the distribution of level splittings. The mean level splitting is found to have oscillations as a function of energy, as expected if scarring plays a role in determining the size of the splittings, and the spacing between peaks is observed to be periodic of period {$2\pi\hbar$} in action. Moreover, the size of the oscillations is directly correlated with the strength of scarring. These results are interpreted within the theoretical framework of Creagh and Whelan. The semiclassical limit and finite-{$\hbar$} effects are discussed, and connections are made with reaction rates and resonance widths in metastable wells.Comment: 22 pages, including 11 figure

Avian malaria-mediated population decline of a widespread iconic bird species

Parasites have the capacity to affect animal populations by modifying host survival, and it is increasingly recognised that infectious disease can negatively impact biodiversity. Populations of the house sparrow (Passer domesticus) have declined in many European towns and ities, but the causes of these declines remain unclear. We investigated associations between parasite infection and house sparrow demography across suburban London where sparrow abundance has declined by 71% since 1995. Plasmodium relictum infection was found at higher prevalences (averaging 74%) in suburban London house sparrows than previously recorded in any wild bird population in Northern Europe. Survival rates of juvenile and adult sparrows and population growth rate were negatively related to Plasmodium relictum infection intensity. Other parasites were much less prevalent and exhibited no relationship with sparrow survival and no negative relationship with population growth. Low rates of co-infection suggested sparrows were not immunocompromised. Our findings indicate that P. relictum infection may be influencing house sparrow population dynamics in suburban areas. The demographic sensitivity of the house sparrow to P. relictum infection in London might reflect a recent increase in exposure to this parasite