Sequential Ubiquitination of Ribosomal Protein uS3 Triggers the Degradation of Non-functional 18S rRNA.

18S non-functional rRNA decay (NRD) eliminates non-functional 18S rRNA with deleterious mutations in the decoding center. Dissociation of the non-functional 80S ribosome into 40S and 60S subunits is a prerequisite step for degradation of the non-functional 18S rRNA. However, the mechanisms by which the non-functional ribosome is recognized and dissociated into subunits remain elusive. Here, we report that the sequential ubiquitination of non-functional ribosomes is crucial for subunit dissociation. 18S NRD requires Mag2-mediated monoubiquitination followed by Hel2- and Rsp5-mediated K63-linked polyubiquitination of uS3 at the 212th lysine residue. Determination of the aberrant 18S rRNA levels in sucrose gradient fractions revealed that the subunit dissociation of stalled ribosomes requires sequential ubiquitination of uS3 by E3 ligases and ATPase activity of Slh1 (Rqt2), as well as Asc1 and Dom34. We propose that sequential uS3 ubiquitination of the non-functional 80S ribosome induces subunit dissociation by Slh1, leading to degradation of the non-functional 18S rRNA.

Frequency and clinical features of suicide attempts in elderly patients in Japan.

The objective of this study was to investigate the clinical features of suicide attempts in elderly patients (≥65 years) in Japan. We enrolled 546 patients who attempted suicide and were hospitalized for inpatient treatment. Characteristics were compared between the elderly and non-elderly patients. Compared with the non-elderly group, the incidence of mood disorders was significantly higher and the average length of stay in the intensive care unit and the duration of hospitalization were significantly longer in the elderly group. Elderly patients hospitalized for attempted suicide were more likely to have mood disorders than the non-elderly.

Clinical features of suicide attempts in adults with autism spectrum disorders.

OBJECTIVE: The objective of this study was to investigate the frequency and clinical features of suicide attempts in adults with autism spectrum disorders (ASDs). METHODS: We enrolled 587 consecutive patients aged 18 or over who attempted suicide and were hospitalized for inpatient treatment. Psychiatric diagnoses, suicide attempt frequency and clinical features were compared between ASD and non-ASD patients. RESULTS: Forty-three (7.3%) of the 587 subjects who attempted suicide had ASDs. The incidence of patients with mood disorders was significantly lower (Fisher's Exact Test, P=.043) and that of those with an adjustment disorder was significantly higher (Fisher's Exact Test, P<.001) in the ASD group than in the non-ASD group. The average length of stay at both the hospital and intensive care unit in the ASD group was longer than that in the non-ASD group (z=-2.031, P=.042; z=-2.322, P=.020, respectively). CONCLUSIONS: ASDs should always be a consideration when dealing with suicide attempts in adults at the emergency room.

Blonanserin in the treatment of delirium.

The purpose of the present study was to provide preliminary data on the usefulness and safety of blonanserin for patients with delirium in the intensive care unit (ICU). The charts of 32 consecutive patients with delirium in the ICU were retrospectively reviewed. These patients were treated with blonanserin. A total of 96.6% had reduction in Memorial Delirium Assessment Scale score. The proportion of patients with side-effects was 24.1%. Blonanserin may be effective and safe in the treatment of delirium in the ICU.

Frequency and clinical features of pervasive developmental disorder in adolescent suicide attempts.

OBJECTIVE: The goal of this clinical study was to examine the frequency and clinical features of pervasive developmental disorder (PDD) relative to suicide attempts by adolescents. METHOD: Ninety-four adolescent patients under age 20 participated in this study; it was a consecutive study of individuals who had attempted suicide and had been hospitalized for inpatient treatment. RESULTS: Twelve of the 94 subjects (12.8%) were diagnosed with PDD. The ratio of males in the PDD group was higher than that in the non-PDD group (P=.017). There was a significant difference between the two groups regarding the rate of patients having mood or anxiety disorder (P=.037). CONCLUSION: This study indicates that PDD should always be a consideration when dealing with adolescent suicide attempts.

Characteristics of suicide attempters with depressive disorders.

Attempted suicide is known to be an important risk factor of committed suicide. Past studies of the relationship of attempted suicide with mental disorders have shown that it is most closely related to depression. The objective of the present study was to clarify characteristics of depression and measures to prevent committed suicide by comparing depression with other mental disorders. The patients with depression were significantly more often aged, males, married, and used methods other than poisoning by solids or liquids compared with patients with other mental disorders. Particularly, the major risk factors of attempted suicide (i.e. a younger age and the female gender), did not apply to our depressed patients. These results suggest that approaches such as intensive psychiatric treatment may lead to the prevention of committed suicide in older male patients with depression who have attempted suicide.

Changes in mental disorder distribution among suicide attempters in mid-west area of Kanagawa.

To clarify changes in mental disorder distribution in suicide attempters, a comparison was made between the period when an economic recession started (1992, 1993) and the period when the recession became serious (2000). The subjects were 212 suicide attempters admitted to the Emergency Medical Center of Tokai University Hospital during a 2-year period between 1992 and 1993 (group A) and 255 suicide attempters admitted during a 1-year period between January and December 2000 (group B). Mental disorders were classified according to the International Classification of Diseases (10th revision; ICD-10). Distribution was compared between groups A and B and significant differences were observed in mental disorder distribution (P < 0.001). The percentages of subjects with depression, those with neurotic disorders, and those with other disorders were higher in group B than in group A. Conversely, the percentage of subjects with schizophrenia was lower in group B than in group A. Mental disorder distribution in suicide attempters significantly changed. However, it was not certain that this change was related to the economic recession and increased unemployment in Japan.

Early crisis intervention to patients with acute stress disorder in general hospital.

This report presents 2 patients who were diagnosed to have acute stress disorder (ASD), received early psychiatric intervention (crisis intervention as a short-term psychotherapy), and subsequently had good outcome. Encounter with an event that causes psychological trauma may induce post-traumatic stress disorder (PTSD). However, the 2 patients described here have shown no particular mental symptoms for more than 2 years after the event and are leading normal lives. Psychological debriefing as a group used to be regarded as effective for the prevention of PTSD, but early identification of the stress-related disorder and intensive treatment of individual patients is recently considered to be more necessary. Both of the 2 patients presented here showed good outcome, and early crisis intervention in individual patients is suggested to be effective for the treatment of stress-related disorders and prevention of PTSD.

Roles of the enantioselective glutathione S-transferases in cleavage of beta-aryl ether.

Cleavage of the beta-aryl ether linkage is the most important process in lignin degradation. Here we characterize the three tandemly located glutathione S-transferase (GST) genes, ligF, ligE, and ligG, from low-molecular-weight lignin-degrading Sphingomonas paucimobilis SYK-6, and we describe the actual roles of these genes in the beta-aryl ether cleavage. Based on the identification of the reaction product by electrospray ionization-mass spectrometry, a model compound of beta-aryl ether, alpha-(2-methoxyphenoxy)-beta-hydroxypropiovanillone (MPHPV), was transformed by LigF or LigE to guaiacol and alpha-glutathionyl-beta-hydroxypropiovanillone (GS-HPV). This result suggested that LigF and LigE catalyze the nucleophilic attack of glutathione on the carbon atom at the beta position of MPHPV. High-pressure liquid chromatography-circular dichroism analysis indicated that LigF and LigE each attacked a different enantiomer of the racemic MPHPV preparation. The ligG gene product specifically catalyzed the elimination of glutathione from GS-HPV generated by the action of LigF. This reaction then produces an achiral compound, beta-hydroxypropiovanillone, which is further degraded by this strain. Disruption of the ligF, ligE, and ligG genes in SYK-6 showed that ligF is essential to the degradation of one of the MPHPV enantiomers, and the alternative activities which metabolize the substrates of LigE and LigG are present in this strain.

Differential expression of two catechol 1,2-dioxygenases in Burkholderia sp. strain TH2.

Burkholderia sp. strain TH2, a 2-chlorobenzoate (2CB)-degrading bacterium, metabolizes benzoate (BA) and 2CB via catechol. Two different gene clusters for the catechol ortho-cleavage pathway (cat1 and cat2) were cloned from TH2 and analyzed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis showed that while both catechol dioxygenases (CatA1 and CatA2) were produced in BA-grown cells, CatA1 was undetectable when strain TH2 was grown on 2CB or cis,cis-muconate (CCM), an intermediate of catechol degradation. However, production of CatA1 during growth on 2CB or CCM was observed when cat2 genes were disrupted. The difference in the production of CatA1 and CatA2 was apparently due to a difference in inducer recognition by the regulators of the gene clusters. The inducer of CatA1 was found to be BA, not 2CB, by using a 2-halobenzoate dioxygenase gene (cbd) disruptant, which is incapable of transforming (chloro)benzoate. It was also found that CCM or its metabolite acts as an inducer for CatA2. When cat2 genes were disrupted, the growth rate in 2CB culture was reduced while that in BA culture was not. These results suggest that although cat2 genes are not indispensable for growth of TH2 on 2CB, they are advantageous.