The generation of amyloid fibrils from an amyloidogenic polypeptide occurs by a nucleation-dependent process initiated in vitro by seeding the protein solution with preformed fibrils. This phenomenon is evidenced in vivo by the fact that amyloid protein A (AA) amyloidosis in mice is markedly accelerated when the animals are given, in addition to an inflammatory stimulus, an i.v. injection of protein extracted from AA amyloid-laden mouse tissue. Heretofore, the chemical nature of this “amyloid enhancing factor” (AEF) has not been definitively identified. Here we report that the active principle of AEF extracted from the spleen of mice with silver nitrate-induced AA amyloidosis was identified unequivocally as the AA fibril itself. Further, we demonstrated that this material was extremely potent, being active in doses <1 ng, and that it retained its biologic activity over a considerable length of time. Notably, the AEF was also effective when administered orally. Our studies have provided evidence that AA and perhaps other forms of amyloidosis are transmissible diseases, akin to the prion-associated disorders.

The debriefing phase is an important feature of simulation activities for learning. This study applies a sociomaterial perspective on debriefing in interprofessional simulation with medical and nursing students. Sociomaterial perspectives are increasingly being used in order to understand professional practice and learning in new ways, conceptualising professional practice as being embodied, relational and situated in sociomaterial relations. The aim of the study is to explore how debriefing is carried out as a practice supporting students’ interprofessional learning. Eighteen debriefing sessions following interprofessional full-scale manikin-based simulation with nursing and medical students from two different universities were video-recorded and analysed collaboratively by a team of researchers, applying a structured scheme for constant comparative analysis. The findings show how debriefing is intertwined with, and shaped by social and material relationships. Two patterns of enacting debriefing emerged. Debriefing as algorithm was enacted as a protocol-based, closed inquiry approach. Debriefing as laissez-faire was enacted as a loosely structured collegial conversation with an open inquiry approach. The findings indicate that neither an imposed structure of the debriefing, nor the lack of structure assured interprofessional collaboration to emerge as a salient topic for reflection, even though that was an explicit learning objective for the simulation.

This qualitative and longitudinal study focuses on graduate employment and the development of graduate employment paths. The aim of this article is to explore the present professional trajectory from higher education to working life, with particular reference to graduates from two different study programmes at Linköping University in Sweden: Political Science and Psychology. More specifically, the article focuses on how graduates construe their professional trajectories in terms of their envisaged future work as senior students, and later as novice and early-career professionals with 18 and 34 months of work life experience. The results indicate that graduates’ professional identities and vision of their future work change over time. The set of categories, depicting the graduates’ vision and experiences of their professional trajectories, do not seem to follow a specific temporal and logical progression in their career. Rather, they appear in different order and at different points in time after graduation. The results, instead, endorse the discourse of lifelong learning and the need for flexibility and employability on the labour market.

Depletion of Foxp3⁺CD4⁺ regulatory T cells (Treg) in adults results in chronic inflammation and autoimmune disease. However, the impact of transient Treg‐cell depletion on self‐reactive responses is poorly defined. Here, we studied the effect of transient depletion of Treg cells on CD4⁺ T‐cell responses to endogenous self‐antigens. Short‐term ablation of Treg cells in mice resulted in rapid activation of CD4⁺ T cells, increased percentage of IFN‐γ⁺ and Th17 cells in lymphoid organs, and development of autoimmune gastritis. To track self‐reactive responses, we analyzed the activation of naïve gastric‐specific CD4⁺ T cells. There was a dramatic increase in proliferation and acquisition of effector function of gastric‐specific T cells in the stomach draining LNs of Treg‐cell‐depleted mice, compared with untreated mice, either during Treg‐cell depletion or after Treg‐cell reconstitution. Moreover, the hyperproliferation of gastric‐specific T cells in the Treg‐cell‐ablated mice was predominantly antigen‐dependent. Transient depletion of Treg cells resulted in a shift in the ratio of peripheral:thymic Treg cells in the reemerged Treg‐cell population, indicating an altered composition of Treg cells. These findings indicate that transient Treg‐cell depletion results in ongoing antigen‐driven self‐reactive T‐cell responses and emphasize the continual requirement for an intact Treg‐cell population.

Spongiform encephalopathies have been reported to be transmitted by blood transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows similarities with prion disease and amyloid-containing organ-extracts can prime a recipient for the disease. In this systemic form of amyloidosis N-terminal fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main amyloid protein. Initial amyloid deposits appear in the perifollicular region of the spleen, followed by deposits in the liver. We used the established murine model and induced AA-amyloidosis in NMRI mice by intravenous injections of purified amyloid fibrils (‘amyloid enhancing factor’) combined with inflammatory challenge (silver nitrate subcutaneously). Blood plasma and peripheral blood monocytes were isolated, sonicated and re-injected into new recipients followed by an inflammatory challenge during a three week period. When the animals were sacrificed presence of amyloid was analyzed in spleen sections after Congo red staining. Our result shows that some of the peripheral blood monocytes, isolated from animals with detectable amyloid, contained amyloid-seed that primed for AA-amyloid. The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes. Plasma recovered from mice with AA amyloidosis lacked seeding capacity. Amyloid enhancing activity can reside in monocytes recovered from mice with AA-amyloidosis and in a prion-like way trigger amyloid formation in conjunction with an inflammatory disorder. Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant. The monocyte-transfer mechanism should be eligible for the human disease and we point out blood transfusion as a putative route for transfer of amyloidosis.