Elinor Schad

The Co-crystal structure of staphylococcal enterotoxin type A with Zn2+ at 2.7 A resolution. Implications for major histocompatibility complex class II binding.

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 Zn2+ in the high affinity interaction with MHC class II molecules. A high affinity metal binding site was described previously in SEA co-crystallized with Cd2+ in which the metal ion was octahedrally co-ordinated, involving the N-terminal serine. We have now co-crystallized SEA with its native co-factor Zn2+ and determined its crystal structure at 2.7 Å resolution. As expected for a Zn2+ ion, the co-ordination was found to be tetrahedral. Three of the ligands are located on the SEA surface on a C-terminal domain β-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 Zn2+ with an affinity of KD = 0.3 μM in an entropy driven process. The differential Zn2+ co-ordination observed here has implications for the mechanism of the SEA-MHC class II interaction.

STAPHYLOCOCCAL ENTEROTOXINS A, D, AND E : STRUCTURE AND FUNCTION, INCLUDING MECHANISM OF T-CELL SUPERANTIGENICITY

Abstract Staphylococcal enterotoxins (SEs) are a family of structurally related exotoxin molecules produced by certain Gram-positive Staphylococcus aureus bacterial strains. SEs are a major cause of food poisoning and are involved in bacterial Gram-positive shock in humans. SEs bind to major histocompatibility complex (MHC) class II molecules on antigen-presenting cells (APCs) and subsequently activate a large fraction, 5–20%, of T lymphocytes (1). This property has led to their classification of superantigens (SAg). The T cells are activated by SAg to proliferate and produce cytokines such as interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor-α and β (TNF-α and β) (2,3). Depending on origin, superantigens can be divided in two groups, viral and bacterial. For reviews see Refs. 4–8.

Factors contributing to the perpetration of workplace incivility: the importance of organizational aspects and experiencing incivility from others

ABSTRACT 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.

Genetically engineered superantigens in experimental tumor therapy

ConclusionsThe data discussed in this review demonstrates that genetically engineered superantigens are highly effective anti-tumor agents in an experimental murine tumor model. The tumor-suppressive activity of Fab-SEA fusion proteins has been shown against established B16 lung metastases and recently also demonstrated against disseminated human colon carcinomas in SCID mice engrafted with human lymphocytes [9, 24]. The local response involves a pronounced infiltration and activation of CD4+ and CD8+ T lymphocytes. Fab-SEA proteins direct CTL against antigen-positive tumor cells and induce local release of tumor-suppressive cytokines. In situ expression of cytokines in the tumor may be particularly important in elimination of antigen-negative tumor cells inevitably present in any tumor. We have also shown that it is feasible to reduce the systemic toxicity and simultaneously retain the therapeutic efficacy of Fab-SEA fusion proteins by means of site-directed mutageneses of amino acids critical for MHC class II binding. The C215Fab-SEAD227A mutant had an estimated Kd of 10-9 M for the tumor antigen compared to Kd of less than 10-5 for the interaction with MHC class II molecules, giving the fusion protein a 10000-fold preference for the tumor antigen versus MHC class II molecules compared to a 100-fold difference for the wild-type C215Fab-SEA for the tumor antigen. It is likely, however, that the optimal MHC class II binding of SEA may vary in different clinical indications. If the targeted tumors such as lymphomas and leukemias, express MHC class II, it may be favorable to retain the affinity for MHC class II at a moderate level, since SEA induced cross-linking of MHC class II on the tumor cell might increase expression of co-stimulatory signals (Fig. 7). Similarly, during therapy of certain solid tumors, release of inflammatory cytokines by tumor-infiltrating MHC class II+ monocytes, may be influenced by MHC class II cross-linking, and thereby facilitate tumor uptake of the Fab-SEA protein.

No time to talk! Teachers’ perceptions of organizational communication: Context and climate

Teachers’ perceptions of organizational communication were assessed using a tailored questionnaire, sampling 401 primary and lower secondary school teachers from two municipalities in Sweden. Overall, the teachers were satisfied with the workplace communication climate, the communication structure, and collegial communication; however, a lack of time for communication was reported. Using a job demands–resource framework and hierarchical linear regression, the organizational communication variables were shown to predict job satisfaction even when controlling for relevant work environment indicators. In total, the model predicted 49.2% of the variance in job satisfaction. It is argued that school leaders should focus primarily both on providing opportunities for collegial interactions and working actively to improve the communication climate in schools.

Psychologists work situation: : cross-sectional associations between perceived workload, self-rated health and expectations on the future work situation

Objectives Psychologists often experience demanding work situations. Despite their professional training, a high workload may hinder rest and recovery and have negative implications for health and expectations on work. Accordingly, we examined how Swedish psychologists perceived their workload, health and future work situation as well as whether workload was associated with self-rated health and satisfaction with the future work situation. Methods Permanently employed and authorised psychologists (N = 2518 (1910 women and 608 men)), working at least 50% of full-time, were included. The mean age was 46 years (SD 11 years). All were responders to a cross-sectional survey with a response rate of 48% (n = 3240). Workload was assessed with four items, each of which was dichotomized (0 = never to monthly; 1 = weekly to daily) and summed into an index score reflecting increasing workload (range 0–4). Self-rated health was assessed with one item (dichotomized into “poor/less good” or “good/very good/excellent”) as was expectations on the future work situation (dichotomized into “very satisfied/satisfied” or “dissatisfied/very dissatisfied”). Results Poor self-rated health was reported by 14.6% and 40.1% reported high workload on at least three of the four workload items. In total 37.6% expressed some degree of dissatisfaction regarding the future work situation. Age and gender adjusted logistic regression analyses showed that increasing workload was associated with increasing reports of poor self-rated health (OR = 1.32, 95% CI = 1.20 to 1.45, p < 0.001) and dissatisfaction regarding the future expectations on work (OR = 1.26, 95% CI = 1.18 to 1.34, p < 0.001). Conclusion Reports of high workload and dissatisfaction over the expected future work situation were common. That a high workload was associated with poor self-rated health and dissatisfaction over the future work situation suggests the existence of a potentially ungainful mismatch between the person and the environment, regarding both health and occupational function.