RESUMO
In the yeast Saccharomyces cerevisiae and other ascomycetes, the maintenance of cell wall integrity is governed by a family of plasma-membrane spanning sensors that include the Wsc-type proteins. These cell wall proteins apparently sense stress-induced mechanical forces at the cell surface and target the cell wall integrity (CWI) signaling pathway, but the structural base for their sensor function is yet unknown. Here, we solved a high-resolution crystal structure of the extracellular cysteine-rich domain (CRD) of yeast Wsc1, which shows the characteristic PAN/Apple domain fold with two of the four Wsc1 disulfide bridges being conserved in other PAN domain cores. Given the general function of PAN domains in mediating protein-protein and protein-carbohydrate interactions, this finding underpins the importance of Wsc domains in conferring sensing and localization functions. Our Wsc1 CRD structure reveals an unusually high number of surface-exposed aromatic residues that are conserved in other fungal CRDs, and can be arranged into three solvent-exposed clusters. Mutational analysis demonstrates that two of the aromatic clusters are required for conferring S. cerevisiae Wsc1-dependent resistance to the glucan synthase inhibitor caspofungin, and the chitin-binding agents Congo red and Calcofluor white. These findings suggest an essential role of surface-exposed aromatic clusters in fungal Wsc-type sensors that might include an involvement in stress-induced sensor-clustering required to elicit appropriate cellular responses via the downstream CWI pathway.
RESUMO
Background: Open-door policies in psychiatry are discussed as a means to improve the treatment of involuntarily committed patients in various aspects. Current research on open-door policies focuses mainly on objective effects, such as the number of coercive interventions or serious incidents. The aim of the present study was to investigate more subjective perceptions of different psychiatric inpatient settings with different door policies by analyzing ward atmosphere and patient satisfaction. Methods: Quantitative data on the ward atmosphere using the Essen Climate Evaluation Scale (EssenCES) and on patient satisfaction (ZUF-8) were obtained from involuntarily committed patients (n = 81) in three psychiatric hospitals with different ward settings and door policies (open, facultative locked, locked). Furthermore, qualitative interviews with each of 15 patients, nurses, and psychiatrists were conducted in one psychiatric hospital with a facultative locked ward comparing treatment in an open vs. a locked setting. Results: Involuntarily committed patients rated the EssenCES' subscale "Experienced Safety" higher in an open setting compared with a facultative locked and a locked setting. The subscale "Therapeutic Hold" was rated higher in an open setting than a locked setting. Regarding the safety experienced from a mental health professionals' perspective, the qualitative interviews further revealed advantages and disadvantages of door locking in specific situations, such as short-term de-escalation vs. increased tension. Patient satisfaction did not differ between the hospitals but correlated weakly with the EssenCES' subscale "Therapeutic Hold." Conclusion: Important aspects of the ward atmosphere seem to be improved in an open vs. a locked setting, whereas patient satisfaction does not seem to be influenced by the door status in the specific population of patients under involuntary commitment. The ward atmosphere turned out to be more sensitive to differences between psychiatric inpatient settings with different door policies. It can contribute to a broader assessment by including subjective perceptions by those who are affected directly by involuntary commitments. Regarding patient satisfaction under involuntary commitment, further research is needed to clarify both the relevance of the concept and its appropriate measurement.
