Pur-alpha functionally interacts with FUS carrying ALS-associated mutations.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder due to motor neuron loss. Fused in sarcoma (FUS) protein carrying ALS-associated mutations localizes to stress granules and causes their coalescence into larger aggregates. Here we show that Pur-alpha physically interacts with mutated FUS in an RNA-dependent manner. Pur-alpha colocalizes with FUS carrying mutations in stress granules of motoneuronal cells differentiated from induced pluripotent stem cells and that are derived from ALS patients. We observe that both Pur-alpha and mutated FUS upregulate phosphorylation of the translation initiation factor eukaryotic translation initiation factor 2 alpha and consistently inhibit global protein synthesis. In vivo expression of Pur-alpha in different Drosophila tissues significatively exacerbates the neurodegeneration caused by mutated FUS. Conversely, the downregulation of Pur-alpha in neurons expressing mutated FUS significatively improves fly climbing activity. All these findings suggest that Pur-alpha, through the control of mRNA translation, might be involved in the pathogenesis of ALS associated with the mutation of FUS, and that an alteration of protein synthesis may be directly implicated in the disease. Finally, in vivo RNAi-mediated ablation of Pur-alpha produced locomotion defects in Drosophila, indicating a pivotal role for this protein in the motoneuronal function.

Recurrent chromosome 6 abnormalities in malignant mesothelioma.

The long latency period between asbestos exposure and the onset of malignant mesothelioma (MM) suggests that a multistep tumorigenesis process occurs whilst the capability of asbestos fibres to interfere directly with chromosomes focuses on the critical role of the chromosomal abnormalities in this neoplasm. The aim of our study was to identify any recurrent chromosomal changes in ten primary MM cell cultures derived from pleural effusions of patients with MM from the same geographic area and environmental and/or occupational exposure to asbestos fibers. Cytogenetic analysis was performed in accordance with International System for Human Cytogenetic Nomenclature. Our results confirmed a great number of cytogenetic abnormalities in MM cells. Recurrent loss of the long arms of chromosome 6 (6q-) was the most frequent abnormality detected (four epithelial and two mixed subtypes) while, on the whole, abnormalities of chromosome 6 were found in nine out of ten cases whereas chromosome 6 was normal only in the case with fibromatous subtype. Monosomy 13 and 17 was found in five cases, monosomy 14 in four cases and 22 in three cases. Since deletion of 6q- was detected even in relatively undisturbed karyotype, we hypothesize a multistep carcinogenic process in which deletion of 6q- is an early event in the development and progression of malignant mesothelioma.

Cigarette smoking in alcohol and cocaine abusers.

This study compared the cigarette smoking of substance abusers whose primary substance of abuse was cocaine (cocaine group: n = 18) or alcohol (alcohol group: n = 23). Cigarette smoking and smoking topography was assessed daily (via self-report and single cigarette topography assessments) at baseline and following a switch to a cigarette brand with 30% lower nicotine. The alcohol and cocaine groups did not differ at baseline on cigarettes smoked per day, cigarette nicotine, smoking topography, or the Fagerstrom Tolerance Questionnaire. However, the cocaine group exhibited marked increases in compensatory smoking relative to the alcohol group following the 30% reduction in cigarette nicotine, as evidenced by decreases in the average time interval between each puff, p < .05, increases in the total amount of time spent puffing, p < .05, and increases in estimated total amount of time spent puffing per day, p < .05. These findings provide initial data that cocaine and alcohol abusers may titrate nicotine differently and suggest that cocaine abusers may require additional or modified smoking cessation treatments.

A cognitive-behavioral therapeutic community for substance dependent and homeless veterans: treatment outcome.

This paper presents data regarding a residential rehabilitation program that integrates cognitive-behavioral and therapeutic community techniques to treat homelessness and substance abuse. The study cohort was 110 military veterans admitted to a Domiciliary Care for Homeless Veterans program of the Department of Veterans Affairs. The cohort had multiple psychosocial problems at admission, and all had drug/alcohol abstinence as a treatment goal. Structured interviews conducted at 3, 6, 9, and 12 months postdischarge revealed that a substantial proportion had positive outcomes with respect to housing, substance abuse abstinence, employment, and self-rated psychological symptoms. This integrated cognitive-behavioral therapeutic community approach appears to be a viable treatment for this subset of homeless and also may be effective for other populations with similar clinical characteristics.

Nightmare prevalence in the healthy elderly.

Fifty-one healthy elderly subjects (median age = 65) gave retrospective estimates of nightmare frequency in questionnaires and recorded the occurrence of nightmares in daily logs over a 2-week period. (a) Mean annual nightmare frequency as estimated from logs was only 65% as high among college student controls. (b) Elderly subjects were about 1/5 as likely as college students to report a problem with nightmares. (c) Frequency estimates on the basis of logs were over 10 times higher than retrospective estimates.