Investigating how mindfulness promotes the restorative effects of nature exposure in virtual reality

Over the last century, the number of people living in urban areas has been increasing and the general health and happiness of the public has been decreasing (Emfield & Neider, 2014). As more people move into urban environments, the negative consequences of reduced connection with nature are becoming more apparent. One promising way to reverse this trend is by reconnecting humans with the natural world. Natural environments have been shown to exert beneficial influences on mental health; however, to effectively develop therapeutic interventions, there is a strong need to understand the mechanisms of action by which natural environments support positive mental health outcomes. This thesis investigated potential mechanisms of action for therapeutic nature exposure as well as the preliminary efficacy of nature exposure therapy in virtual reality. Research subjects completed a survey measure assessing previous visits to nature and self-reported mental health symptoms. They subsequently completed an in situ experimental session in which they received one of three treatments (real nature, virtual nature or no nature) and then completed a laboratory stress task. Levels of mindfulness during the stressor and changes in self-reported levels of state positive and negative affect before and after the stressor were assessed. Results showed nature visitation indirectly correlated with psychopathology and emotional responses to nature. Additionally, mindfulness covaried with nature treatment type (real nature or virtual nature) for positive affect. These results elucidate the relationship between nature and mental health and demonstrate the potential for virtual restorative environments to be used in the treatment of mental health disorders

Augmenting Immersive Telepresence Experience with a Virtual Body

We propose augmenting immersive telepresence by adding a virtual body, representing the user's own arm motions, as realized through a head-mounted display and a 360-degree camera. Previous research has shown the effectiveness of having a virtual body in simulated environments; however, research on whether seeing one's own virtual arms increases presence or preference for the user in an immersive telepresence setup is limited. We conducted a study where a host introduced a research lab while participants wore a head-mounted display which allowed them to be telepresent at the host's physical location via a 360-degree camera, either with or without a virtual body. We first conducted a pilot study of 20 participants, followed by a pre-registered 62 participant confirmatory study. Whereas the pilot study showed greater presence and preference when the virtual body was present, the confirmatory study failed to replicate these results, with only behavioral measures suggesting an increase in presence. After analyzing the qualitative data and modeling interactions, we suspect that the quality and style of the virtual arms, and the contrast between animation and video, led to individual differences in reactions to the virtual body which subsequently moderated feelings of presence.Comment: Accepted for publication in Transactions in Visualization and Computer Graphics (TVCG), to be presented in IEEE VR 202

Virtual Reality Sickness Reduces Attention During Immersive Experiences

In this paper, we show that Virtual Reality (VR) sickness is associated with a reduction in attention, which was detected with the P3b Event-Related Potential (ERP) component from electroencephalography (EEG) measurements collected in a dual-task paradigm. We hypothesized that sickness symptoms such as nausea, eyestrain, and fatigue would reduce the users' capacity to pay attention to tasks completed in a virtual environment, and that this reduction in attention would be dynamically reflected in a decrease of the P3b amplitude while VR sickness was experienced. In a user study, participants were taken on a tour through a museum in VR along paths with varying amounts of rotation, shown previously to cause different levels of VR sickness. While paying attention to the virtual museum (the primary task), participants were asked to silently count tones of a different frequency (the secondary task). Control measurements for comparison against the VR sickness conditions were taken when the users were not wearing the Head-Mounted Display (HMD) and while they were immersed in VR but not moving through the environment. This exploratory study shows, across multiple analyses, that the effect mean amplitude of the P3b collected during the task is associated with both sickness severity measured after the task with a questionnaire (SSQ) and with the number of counting errors on the secondary task. Thus, VR sickness may impair attention and task performance, and these changes in attention can be tracked with ERP measures as they happen, without asking participants to assess their sickness symptoms in the moment

Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu

Overexpression of the transmembrane receptor tyrosine kinase ErbB2 is common in multiple malignancies, including breast and ovarian cancer. ErbB2 is resistant to degradation mediated by c-Cbl, the E3 ubiquitin ligase responsible for ligand-induced ubiquitination of ErbB1 (epidermal growth factor receptor). Because of its resistance to degradation, ErbB2 is the preferred dimerization partner for other members of the ErbB family, and its overexpression in vivo is associated with poor prognosis. We now show that the chaperone-binding ubiquitin ligase CHIP efficiently ubiquitinates and down-regulates ErbB2. CHIP expression shortens the half-life of both nascent and mature ErbB2 protein. In vitro ubiquitination assay shows that CHIP serves as a ubiquitin ligase for ErbB2, and both exogenously expressed and endogenous CHIP coprecipitate with the kinase. Furthermore, CHIP association with ErbB2 requires a chaperone intermediate and is increased by the chaperone-binding drug geldanamycin, a potent stimulator of ErbB2 ubiquitination and degradation. These data describe a previously unrecognized pathway, amenable to pharmacologic manipulation, that mediates ErbB2 stability

Prognostic implications of carboxyl-terminus of Hsc70 interacting protein and lysyl-oxidase expression in human breast cancer

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2010 Patani.Background: Ubiquitin modification of proteins influences cellular processes relevant to carcinogenesis. CHIP (carboxyl-terminus of Hsc70-interacting protein) is a chaperone-dependent E3 ubiquitin ligase, regulating the stability of heat shock protein 90 (HSP90) interacting proteins. CHIP is implicated in the modulation of estrogen receptor (ESR1) and Her-2/neu (ERBB2) stability. LOX (lysyl-oxidase) serves intracellular roles and catalyses the cross-linking of extracellular matrix (ECM) collagens and elastin. LOX expression is altered in human malignancies and their peri-tumoral stroma. However, paradoxical roles are reported. In this study, the level of mRNA expression of CHIP and LOX were assessed in normal and malignant breast tissue and correlated with clinico-pathological parameters. Materials and Methods: Breast cancer (BC) tissues (n = 127) and normal tissues (n = 33) underwent RNA extraction and reverse transcription; transcript levels were determined using real-time quantitative PCR and normalized against CK-19. Transcript levels were analyzed against TNM stage, nodal involvement, tumor grade and clinical outcome over a ten-year follow-up period. Results: CHIP expression decreased with increasing Nottingham Prognostic Index (NPI): NPI-1 vs. NPI-3 (12.2 vs. 0.2, P = 0.0264), NPI-2 vs. NPI-3 (3 vs. 0.2, P = 0.0275). CHIP expression decreased with increasing TNM stage: TNM-1 vs. TNM-2 (12 vs. 0, P = 0.0639), TNM-1 vs. TNM-2-4 (12 vs. 0, P = 0.0434). Lower transcript levels were associated with increasing tumor grade: grade 1 vs. grade 3 (17.7 vs. 0.3, P = 0.0266), grade 2 vs. grade 3 (5 vs. 0.3, P = 0.0454). The overall survival (OS) for tumors classified as ‘low-level expression’, was poorer than those with ‘high-level expression’ (118.1 vs. 152.3 months, P = 0.039). LOX expression decreased with increasing NPI: NPI-1 vs. NPI-2 (3 vs. 0, P = 0.0301) and TNM stage: TNM-1 = 3854639, TNM-2 = 908900, TNM-3 = 329, TNM-4 = 1.232 (P = NS). Conclusion: CHIP expression is associated with favorable prognostic parameters, including tumor grade, TNM stage and NPI. CHIP expression predicts OS. LOX expression is associated with improved NPI. In addition to their prognostic utility, mechanistic insights into tumor suppressor function may offer potential therapeutic strategies

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Sperm protein 17 is a novel marker for predicting cisplatin response in esophageal squamous cancer cell lines

Expression of sperm protein 17 (Sp17) mRNA has been reported in various malignancies. In an earlier study, we reported the upregulation of Sp17 transcripts in primary esophageal squamous cell carcinomas (ESCCs) using differential display and detected Sp17 transcripts in 86% of ESCCs by RT-PCR, whereas no transcripts were detected in the paired normal esophageal tissues. Herein we hypothesized that Sp17 might be used as a marker for detecting the response of anticancer therapies in ESCCs. Our results indicated that Sp17 protein levels in esophageal squamous cancer cell lines decreased in response to treatment with ( i ) the HSP90 activity inhibitor geldanamycin, ( ii ) the tyrosine kinase inhibitor erlotinib and ( iii ) cisplatin (chemotherapeutic agent commonly used in management of ESCC). In contrast, the Sp17 levels did not decrease in response to radiation therapy and treatment with the chemotherapeutic agent, gemcitabine. Further investigations showed that cisplatin induced decrease in Sp17 levels was due to transcriptional inhibition and cisplatin-resistant cell lines did not show this decrease in Sp17 levels in response to cisplatin treatment. In addition, we also carried our mass spectophotometric analysis to identify the binding partners of Sp17 to characterize its possible involvement in esophageal tumorigenesis and chemoresistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64923/1/24828_ftp.pd

Quality control in oocytes by p63 is based on a spring-loaded activation mechanism on the molecular and cellular level.

Mammalian oocytes are arrested in the dictyate stage of meiotic prophase I for long periods of time, during which the high concentration of the p53 family member TAp63α sensitizes them to DNA damage-induced apoptosis. TAp63α is kept in an inactive and exclusively dimeric state but undergoes rapid phosphorylation-induced tetramerization and concomitant activation upon detection of DNA damage. Here we show that the TAp63α dimer is a kinetically trapped state. Activation follows a spring-loaded mechanism not requiring further translation of other cellular factors in oocytes and is associated with unfolding of the inhibitory structure that blocks the tetramerization interface. Using a combination of biophysical methods as well as cell and ovary culture experiments we explain how TAp63α is kept inactive in the absence of DNA damage but causes rapid oocyte elimination in response to a few DNA double strand breaks thereby acting as the key quality control factor in maternal reproduction