Staphylococcal enterotoxins are prototype superantigens characterized by their ability to bind to major histocompatibility complex (MHC) class II molecules and subsequently activate a large fraction of T‐lymphocytes. The crystal structure of staphylococcal enterotoxin type A (SEA), a 27 kDa monomeric protein, was determined to 1.9 A resolution with an R‐factor of 19.9% by multiple isomorphous replacement. SEA is a two domain protein composed of a beta‐barrel and a beta‐grasp motif demonstrating the same general structure as staphylococcal enterotoxins SEB and TSST‐1. Unique for SEA, however, is a Zn2+ coordination site involved in MHC class II binding. Four amino acids including Ser1, His187, His225 and Asp227 were found to be involved in direct coordination of the metal ion. SEA is the first Zn2+ binding enterotoxin that has been structurally determined.
In recent years a growing amount of research has been conducted in the area of workplace incivility. Whereas many studies have focused on the victims and the consequences of incivility, little attention has been paid to the perpetrators and antecedents of workplace incivility. This study aims to identify possible antecedents of workplace incivility, by investigating organizational aspects as well as the possibility that being the target of incivility from co-workers and supervisors could induce incivility. A total of 512 employees (378 women and 133 men) in the school sector in a Swedish municipality completed an online questionnaire. Overall, the results of structural equation modelling analyses showed that organizational variables were related to the perpetration of incivility. A direct relationship was found between being uncivil and organizational change, job insecurity, low social support from co-workers and high job demands. However, the strongest relationship was found between experienced incivility from co-workers and instigated incivility. This could be reflecting a climate or culture of incivility in the organization, and carry implications for future practice in interventions against workplace incivility. The results indicate the importance of focusing on the perspective of the instigator to gain knowledge about the process of workplace incivility.
Superantigens form complexes with major histocompatibility complex (MHC) class II molecules and T-cell receptors resulting in extremely strong immunostimulatory properties. Staphylococcus aureus enterotoxin A (SEA) belongs to a subgroup of the staphylococcal superantigens that utilizes Zn 2؉ in the high affinity interaction with MHC class II molecules. A high affinity metal binding site was described previously in SEA cocrystallized with Cd 2؉ in which the metal ion was octahedrally co-ordinated, involving the N-terminal serine. We have now co-crystallized SEA with its native cofactor Zn 2؉ and determined its crystal structure at 2.7 Å resolution. As expected for a Zn 2؉ ion, the co-ordination was found to be tetrahedral. Three of the ligands are located on the SEA surface on a C-terminal domain -sheet, while the fourth varies with the conditions. Further analysis of the zinc binding event was performed using titration microcalorimetry, which showed that SEA binds Zn 2؉ with an affinity of K D ؍ 0.3 M in an entropy driven process. The differential Zn 2؉ co-ordination observed here has implications for the mechanism of the SEA-MHC class II interaction.Superantigens bind as nonprocessed proteins to major histocompatibility (MHC) 1 class II molecules on antigen presenting cells and subsequently activate T-lymphocytes by interactions with T-cell receptors. Superantigen activated T-cells proliferate vigorously, and subsequently T-cell and monocyte derived cytokines are produced in large amounts. The released cytokines contribute to the development of toxin-induced disease processes (for a review see Ref. 1).The best characterized superantigens are the staphylococcal enterotoxins. Based on sequence similarity, these may be divided into two subgroups: the first consists of staphylococcal enterotoxins A, D, E, and H (SEA SED, SEE, and SEH) and the second of staphylococcal enterotoxins B and C1-C3 (SEB, SEC1, SEC2, and SEC3) (reviewed in Ref.2). The sequence identity of SEA to other staphylococcal enterotoxins ranges from 25 (SEC1) to 83% (SEE). In addition, SEA, SED, and SEE are all dependent on Zn 2ϩ for high affinity binding to MHC class II molecules in contrast to SEB and SEC1-3 that bind MHC class II molecules independently of metal ions (3).Recently solved crystal structures of the free forms of SEA (4), SEB (5), SEC2 (6), and toxic shock syndrome toxin 1 (7, 8), as well as of the SEB-MHC class II complex (9), have created an understanding for the structural constraints by which superantigens interact with their target receptors. The structure of SEB, bound to a MHC class II molecule, confirmed that the superantigen binds to the ␣-chain of the MHC class II molecule, outside the peptide antigen-binding groove. The more distantly related superantigen, toxic shock syndrome toxin 1, binds in a fashion similar to that of SEB, although it covers a larger area on the receptor and in addition utilizes a bound peptide antigen in the interactions (10).Site-directed mutagenesis of SEA confirmed that co-ordination of Zn 2ϩ ...
Purpose: The aim of the study was to investigate the participating psychologists' experiences with compassion fatigue, and to identify individual, interpersonal, and organizational factors and strategies perceived as contributing or protecting in relation to compassion fatigue. Methods: Semi-structured telephone interviews were conducted with eight psychologists (three men and five women) with more than five years of experience in clinical practice. The interviews were analyzed with thematic analysis, generating five themes. Results: These were organizational and task specific factors which the participants felt contributed to their compassion fatigue ("mission impossible" and "emotional strain"), experiences of compassion fatigue ("consequences"), interpersonal factors that were perceived as contributing or protecting ("interpersonal factors"), and individual factors that were perceived as protecting ("shielding and strengthening factors"). Conclusions: It was found that all of the participants had experienced negative impact of compassion fatigue on their personal lives. A large quantity of patients, and complex patient cases, as well as high expectations on the psychologists were experienced as contributing factors. Collegial support, an empathetic boss, a high degree of agency at work, and fulfiling activities outside of work were experienced as protecting against compassion fatigue.
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