Impact of a Virtual Reality-Based Simulation on Empathy and Attitudes Toward Schizophrenia.

Virtual Reality (VR) has been identified as one of the most promising resources for developing empathy towards stigmatized groups as it allows individuals to experience a situation close to reality from another person's perspective. This quasi-experimental study aimed to examine the impact on empathy, knowledge, and attitudes towards people with schizophrenia of a VR simulation that reproduces the experience of psychotic symptoms while performing a cognitive task compared with watching a 2D video and, thus, how these experiences could reduce stigma towards people diagnosed with schizophrenia. The sample comprised of 102 higher education health students, distributed by the experimental and control groups. The impact of the program was measured by completing multiple questionnaires on levels of empathy, attitudes, and mental health knowledge. Both methods (VR and 2D video) were, to a certain extent, effective. However, VR was more effective at eliciting attitudes and knowledge change compared to the control group. These findings suggest that not only VR but also 2D videos could be interesting strategies to enhance empathy and improve attitudes towards people with schizophrenia in higher education health students.

Development of weCope, a mobile app for illness self-management in schizophrenia

Abstract Objective To describe the development of weCope, a Portuguese mobile app for people with schizophrenia. Methods The development of weCope followed 4 stages: I-102 people with psychotic disorders completed an online questionnaire; II-a multidisciplinary focus group was conducted among five mental health professionals; III-we developed the app; IV-9 participants used weCope during 8 weeks to assess its efficiency. Results weCope targets coping with voices, problem solving, goals setting and stress management, and results indicated that: weCope improved symptoms, sense of recovery and personal and social functioning; 59% of the participants were willing to download an application for illness self-management; professionals revealed some concerns about mHealth but enhanced the high importance to develop these apps; usability testing revealed that 89% considered weCope useful for illness self-management. However, the more years with mental illness, the less importance is given to a mobile application for this purpose. Discussion weCope was developed through a comprehensive development process and may contribute to a subjective perception of the patient's better well-being and health condition.

Biochemical and biophysical characterization of recombinant yeast proteasome maturation factor ump1.

Protein degradation is essential for maintaining cellular homeostasis. The proteasome is the central enzyme responsible for non-lysosomal protein degradation in eukaryotic cells. Although proteasome assembly is not yet completely understood, a number of cofactors required for proper assembly and maturation have been identified. Ump is a short-lived maturation factor required for the efficient biogenesis of the 20S proteasome. Upon the association of the two precursor complexes, Ump is encased and is rapidly degraded after the proteolytic sites in the interior of the nascent proteasome are activated. In order to further understand the mechanisms behind proteasomal maturation, we expressed and purified yeast Ump in E. coli for biophysical and structural analysis. We show that recombinant Ump is purified as a mixture of different oligomeric species and that oligomerization is mediated by intermolecular disulfide bond formation involving the only cysteine residue present in the protein. Furthermore, a combination of bioinformatic, biochemical and structural analysis revealed that Ump shows characteristics of an intrinsically disordered protein, which might become structured only upon interaction with the proteasome subunits.

The C-terminal extension of the beta7 subunit and activator complexes stabilize nascent 20 S proteasomes and promote their maturation.

The eukaryotic 20 S proteasome is formed by dimerization of two precursor complexes containing the maturation factor Ump1. Beta7/Pre4 is the only one of the 14 subunits forming the 20 S proteasome that is absent from these precursor complexes in Saccharomyces cerevisiae. Increased expression of Pre4 leads to a reduction in the level of precursor complex, indicating that Pre4 incorporation into these complexes is rate-limiting for their dimerization. When we purified these precursor complexes, we observed co-purification of Blm10, a large protein known to attach to the alpha ring surface of proteasomes. In contrast to single mutants lacking either Blm10 or the C-terminal extension of Pre4, a mutant lacking both grew extremely poorly, accumulated very high levels of precursor complexes, and was impaired in beta subunit maturation. The effect of blm10Delta on proteasome biogenesis is modest, apparently because the 19 S regulatory particle is capable of substituting for Blm10, as long as precursor complex dimers are stabilized by the Pre4 C terminus. We found that a mutation (sen3/rpn2) affecting the Rpn2 subunit inhibits attachment of the 19 S activator to the 20 S particle or its precursors. Although the sen3 mutation alone had no apparent effect on precursor complex dimerization and active site maturation, the sen3 blm10 double mutant was impaired in these processes. Together these data demonstrate that Blm10 and the 19 S activator have a partially redundant function in stabilizing nascent 20 S proteasomes and in promoting their activation.

Biting the hand that feeds: Rpn4-dependent feedback regulation of proteasome function.

The 26S proteasome of eukaryotic cells mediates ubiquitin-dependent as well as ubiquitin-independent degradation of proteins in many regulatory processes as well as in protein quality control. The proteasome itself is a dynamic complex with varying compositions and interaction partners. Studies in Saccharomyces cerevisiae have revealed that expression of proteasome subunit genes is coordinately controlled by the Rpn4 transcriptional activator. The cellular level of Rpn4 itself is subject to a complex regulation, which, aside of a transcriptional control of its gene, intriguingly involves ubiquitin-dependent as well as ubiquitin-independent control of its stability by the proteasome. A novel study by Ju et al. [D. Ju, H. Yu, X. Wang, Y. Xie, Ubiquitin-mediated degradation of Rpn4 is controlled by a phosphorylation-dependent ubiquitylation signal, Biochim. Biophys. Acta (in press), doi:10.1016/j.bbamcr.2007.04.012] now revealed another level of complexity by showing that phosphorylation of a specific serine residue in Rpn4 is required for its efficient targeting by the Ubr2 ubiquitin ligase.

Role of C-terminal extensions of subunits beta2 and beta7 in assembly and activity of eukaryotic proteasomes.

A close inspection of the crystal structure of the yeast 20 S proteasome revealed that a prominent connection between the two beta-rings is mediated by the subunit beta7/Pre4. Its C-terminal extension intercalates between the beta1/Pre3 and beta2/Pup1 subunits on the opposite ring. We show that the interactions promoted by the beta7/Pre4 tail are important to facilitate the formation of 20 S particles from two half-proteasome precursor complexes and/or to stabilize mature 20 S proteasomes. The deletion of 19 residues from the beta7/Pre4 C terminus leads to an accumulation of half-proteasome precursor complexes containing the maturation factor Ump1. The C-terminal extension of beta7/Pre4, which forms several hydrogen bonds with beta1/Pre3, is in addition required for the post-acidic activity mediated by the latter subunit. Deletion of the C-terminal tail of beta7/Pre4 results in an inhibition of beta1/Pre3 propeptide processing and abrogation of post-acidic activity. Our data obtained with yeast strains that expressed the mature form of Pre3 lacking its propeptide suggest that interactions between the Pre4 C terminus and Pre3 stabilize a conformation of its active site, which is essential for post-acidic activity. Deletion of the C-terminal extension of beta2/Pup1, which wraps around beta3/Pup3 within the same beta-ring, is lethal, indicating that this extension serves an essential function in proteasome assembly or stability.