Acceptance and commitment therapy combined with vestibular rehabilitation for persistent postural-perceptual dizziness: A pilot study.

PURPOSE: This study investigated the feasibility of acceptance and commitment therapy for persistent postural-perceptual dizziness and preliminarily verified the long-term effectiveness of the therapy. MATERIALS AND METHODS: This study implemented the within-group pre-post comparison design. We enrolled 27 adult patients who met the criteria of persistent postural-perceptual dizziness. They underwent a treatment program including acceptance and commitment therapy combined with vestibular rehabilitation once a week for a total of six sessions. The primary outcome was changes in the Dizziness Handicap Inventory score 6 months posttreatment. RESULTS: All 27 patients completed the acceptance and commitment therapy + vestibular rehabilitation program, and 25 patients (92.6%) could be followed for 6 months posttreatment. For 27 participants, the scores from pretreatment to 6 months posttreatment significantly declined (P < .001), and the Dizziness Handicap Inventory effect size was 1.11 (95% confidence interval = 0.80-1.42). At 6 months posttreatment, 11 patients (40.7%) achieved remission (the score ≤ 14), 16 (59.3%) achieved treatment response (reduction in the score ≥ 18), and 20 (74.1%) achieved remission and/or treatment response. CONCLUSIONS: Acceptance and commitment therapy is feasible for persistent postural-perceptual dizziness and might have long-term effectiveness. However, a randomized controlled trial is warranted.

Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt.

Wingless (Wg)/Wnt has been proposed to exert various functions as a morphogen depending on the levels of its signalling. Therefore, not just the concentration of Wg/Wnt, but also the responsiveness of Wg/Wnt-target cells to the ligand, must have a crucial function in controlling cellular outputs. Here, we show that a balance of ubiquitylation and deubiquitylation of the Wg/Wnt receptor Frizzled determines the cellular responsiveness to Wg/Wnt both in mammalian cells and in Drosophila, and that the cell surface level of Frizzled is regulated by deubiquitylating enzyme UBPY/ubiquitin-specific protease 8 (USP8). Although ubiquitylated Frizzled underwent lysosomal trafficking and degradation, UBPY/USP8-dependent deubiquitylation led to recycling of Frizzled to the plasma membrane, thereby elevating its surface level. Importantly, a gain and loss of UBPY/USP8 function led to up- and down-regulation, respectively, of canonical Wg/Wnt signalling. These results unveil a novel mechanism that regulates the cellular responsiveness to Wg/Wnt by controlling the cell surface level of Frizzled.

ASK3, a novel member of the apoptosis signal-regulating kinase family, is essential for stress-induced cell death in HeLa cells.

Apoptosis signal-regulating kinase 1 (ASK1) and ASK2 are both members of mitogen-activated protein kinase kinase kinase (MAP3K) family that are implicated in apoptotic cell death, stress responses, and various diseases. We have determined that NT2RI3007443, TESTI4031745, SGK341, and human MAP3K15 are all transcribed from the same genomic locus, which we designate "ASK3 gene" based on sequence homology to ASK1 and ASK2. NT2RI3007443, TESTI4031745, and SGK341 displayed distinct expression profiles among human tissues. TESTI4031745 was expressed in relatively high levels. The expression of TESTI4031745 was increased in rectum tumor and Alzheimer's disease hippocampus and decreased in kidney tumor and Alzheimer's disease frontal lobe. NT2RI3007443 showed moderate levels of ubiquitous expression in normal adult tissues. They did not drastically change in diseases except for increase in cirrhosis liver. Expression of SGK341 was restricted. It was highly expressed in fetal brain, and moderately expressed in normal hippocampus, pancreas, spleen, lung, and kidney. Further, its expression was dramatically increased in hepatic cirrhosis and decreased in lung tumor. Target proteins encoded by NT2RI3007443 and TESTI4031745 were translated in cell-free protein synthesis system. They exhibited protein kinase activity indicated by ATP consumption and phosphorylation of Syntide 2 as a substrate. We demonstrated that knockdown of ASK3 protected HeLa cells against cytotoxicity induced by anti-Fas monoclonal antibody, TNF-alpha, or oxidative stress. These findings suggest that "ASK3 gene" is a novel member of apoptosis signal-regulating kinases and that it plays a pivotal role in the signal transduction pathway implicated in apoptotic cell death triggered by cellular stresses. It can be a putative therapeutic drug target for multiple human diseases.

Cognitive-behavioural therapy for chronic subjective dizziness: Predictors of improvement in Dizziness Handicap Inventory at 6 months posttreatment.

Background: Chronic subjective dizziness (CSD), which was superseded by persistent postural-perceptual dizziness as of 2017, has a great impact on patients' quality of life. Cognitive-behavioural therapy (CBT) is a promising treatment, with demonstrated effectiveness as a CSD treatment; however, no studies have examined positive predictors of its effectiveness in the long term.Aims/objectives: This study aimed to examine predictors of improvement in the Dizziness Handicap Inventory (DHI) in patients with CSD at 6 months after CBT.Materials and methods: Thirty-seven patients with CSD who were recruited from April 2012 to November 2014 and completed group CBT were analysed. Single and multiple regression analyses with forward-backward stepwise model selection method was used to examine the independent predictors of long-term improvement in the change score of DHI.Results: Presence or absence of comorbid anxiety disorders (p = .023) was a significant positive predictive factor for improvement of DHI from pretreatment to 6-month follow-up.Conclusions and significance: The presence of comorbid anxiety disorders predicted considerable improvement of DHI from pretreatment to 6-month follow-up. Group therapy including interoceptive exposure using vestibular rehabilitation, along with psychoeducation and behavioural experiments with graded exposure, may be particularly suitable in treating patients with CSD.

A novel tyrosine-phosphorylated protein inhibiting the growth of Streptomyces cells.

Very few of the tyrosine-phosphorylated proteins in Streptomyces have been identified. Here, we identify a tyrosine-phosphorylated protein from Streptomyces coelicolor A3(2), designated as SCO5717. The protein possesses Walker motifs and a tyrosine cluster at the C-terminus. When sco5717 harboring its own promoter was introduced into the S. coelicolor cell, the growth was inhibited. An sco5717-disrupted mutant formed aerial mycelium earlier than the wild-type strain, suggesting that SCO5717 controls the cell growth of S. coelicolor. Although the recombinant SCO5717 showed an ATPase activity, it lacked self-phosphorylation ability, suggesting that SCO5717 is a novel tyrosine-phosphorylated protein, which is distinguishable from bacterial protein tyrosine kinases known so far.

G-protein-coupled receptor GPR49 is up-regulated in basal cell carcinoma and promotes cell proliferation and tumor formation.

The significance of Hedgehog (HH) signaling in the development of basal cell carcinoma (BCC) has been established. Although several target genes of HH signaling have been described previously, their precise role in tumorigenesis and cell proliferation is not yet known. To identify genes responsible for tumor formation in BCC, we screened a DNA microarray database of human BCC cases; the orphan G-protein-coupled receptor GPR49 was found to be up-regulated in all cases. GPR49 is a novel gene reported to be a marker of follicular and other tissue stem cells. Using real-time quantitative RT-PCR analysis, significant expression of GPR49 mRNA was observed in 19 of 20 BCC cases (95%) compared with controls. Up-regulation of GPR49 was confirmed by in situ hybridization. Moreover, knockdown of mouse Gpr49 showed suppression of cell proliferation in a mouse BCC cell line, and overexpression of GPR49 in human immortalized keratinocyte HaCaT cells induced proliferation. Furthermore, HaCaT cells overexpressing GPR49 showed tumor formation when transplanted into immunodeficient mice. In addition, inhibition of the HH signaling pathway in a mouse BCC cell line down-regulated endogenous Gpr49, whereas activation of HH signaling in mouse NIH3T3 cells up-regulated endogenous GPR49. These results suggest that GPR49 is expressed downstream of HH signaling and promotes cell proliferation and tumor formation in cases of BCC.

RiceGAAS: an automated annotation system and database for rice genome sequence.

An extensive effort of the International Rice Genome Sequencing Project (IRGSP) has resulted in rapid accumulation of genome sequence, and >137 Mb has already been made available to the public domain as of August 2001. This requires a high-throughput annotation scheme to extract biologically useful and timely information from the sequence data on a regular basis. A new automated annotation system and database called Rice Genome Automated Annotation System (RiceGAAS) has been developed to execute a reliable and up-to-date analysis of the genome sequence as well as to store and retrieve the results of annotation. The system has the following functional features: (i) collection of rice genome sequences from GenBank; (ii) execution of gene prediction and homology search programs; (iii) integration of results from various analyses and automatic interpretation of coding regions; (iv) re-execution of analysis, integration and automatic interpretation with the latest entries in reference databases; (v) integrated visualization of the stored data using web-based graphical view. RiceGAAS also has a data submission mechanism that allows public users to perform fully automated annotation of their own sequences. The system can be accessed at http://RiceGAAS.dna.affrc.go.jp/.