Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo

Autoreactive B lymphocytes first encountering self-antigens in peripheral tissues are normally regulated by induction of anergy or apoptosis. According to the "two-signal" model, antigen recognition alone should render B cells tolerant unless T cell help or inflammatory signals such as lipopolysaccharide are provided. However, no such signals seem necessary for responses to T-independent type 2 (TI-2) antigens, which are multimeric antigens lacking T cell epitopes and Toll-like receptor ligands. How then do mature B cells avoid making a TI-2-like response to multimeric self-antigens? We present evidence that TI-2 antigens decorated with ligands of inhibitory sialic acid-binding Ig-like lectins (siglecs) are poorly immunogenic and can induce tolerance to subsequent challenge with immunogenic antigen. Two siglecs, CD22 and Siglec-G, contributed to tolerance induction, preventing plasma cell differentiation or survival. Although mutations in CD22 and its signaling machinery have been associated with dysregulated B cell development and autoantibody production, previous analyses failed to identify a tolerance defect in antigen-specific mutant B cells. Our results support a role for siglecs in B cell self-/nonself-discrimination, namely suppressing responses to self-associated antigens while permitting rapid "missing self"-responses to unsialylated multimeric antigens. The results suggest use of siglec ligand antigen constructs as an approach for inducing tolerance

Spontaneous alloying in binary metal microclusters - A molecular dynamics study -

Microcanonical molecular dynamics study of the spontaneous alloying(SA), which is a manifestation of fast atomic diffusion in a nano-sized metal cluster, is done in terms of a simple two dimensional binary Morse model. Important features observed by Yasuda and Mori are well reproduced in our simulation. The temperature dependence and size dependence of the SA phenomena are extensively explored by examining long time dynamics. The dominant role of negative heat of solution in completing the SA is also discussed. We point out that a presence of melting surface induces the diffusion of core atoms even if they are solid-like. In other words, the {\it surface melting} at substantially low temperature plays a key role in attaining the SA.Comment: 15 pages, 12 fgures, Submitted to Phys.Rev.

PTSD in paramedics: history, conceptual issues and psychometric measures

Post-traumatic stress disorder (PTSD) is more common in paramedics than in the general population because of the stressful and distressing nature of their work. Forms of PTSD associated with chronic stress and repeated trauma are scarcely researched among paramedics. This is striking as this workforce is potentially more likely to be affected by these types of PTSD. Diagnostic processes are still largely based on acute rather than chronic psychological trauma. PTSD diagnosis has been influenced by sociological perceptions of mental illness and changes in diagnostic criteria. Criteria for the diagnosis of PTSD in the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases have changed in the past decade, which may facilitate more appropriate diagnoses of PTSD in paramedics. Paramedics often have a complex aetiology of PTSD resulting from experiences of both chronic and acute events. Questionnaires that cover exposure to both individual and repeated stressful events are required to enable further research in the area of PTSD in paramedics

Structure-activity relationship in HC-SCR of NOx, by TEM, O-2-chemisorption, and EDXS study of Ag/Al2O3

Ag/alumina catalysts with different silver loading (1.28 - 6 wt %) for lean NO reduction activity were prepared by impregnation and the incipient wetness method. Complementary HRTEM, HAADF, O-2-chemisorption, and EDXS studies were applied to investigate the dependence between silver particle size and catalytic activities of the prepared materials. The catalyst with the lowest silver loading (1.28 wt %) was found to be the most active catalyst in terms of reacted NO molecules per mole of silver. On the basis of the HRTEM, HAADF, and O-2-chemisorption studies it could be concluded that the mean particle size or particle size distribution of the samples alone could not explain the big difference in the activities. EDXS analyses showed on the other hand that all of the samples were very heterogeneous in terms of particle size distribution, e.g., including both small and very big particles. Furthermore, both metallic silver and mainly hexagonal silver oxide (Ag2O) were found to be present in the samples. Despite the valuable information provided by ex situ characterization of the prepared samples, it needs to be emphasized that establishing a structure-reactivity relationship for this type of catalyst requires in situ characterization