ABSTRACT
Telomeres are found at the end of chromosomes and are important for chromosome stability. Here we describe a specific telomere-associated protein: TZAP (telomeric zinc finger-associated protein). TZAP binds preferentially to long telomeres that have a low concentration of shelterin complex, competing with the telomeric-repeat binding factors TRF1 and TRF2. When localized at telomeres, TZAP triggers a process known as telomere trimming, which results in the rapid deletion of telomeric repeats. On the basis of these results, we propose a model for telomere length regulation in mammalian cells: The reduced concentration of the shelterin complex at long telomeres results in TZAP binding and initiation of telomere trimming. Binding of TZAP to long telomeres represents the switch that triggers telomere trimming, setting the upper limit of telomere length.
Subject(s)
DNA-Binding Proteins/metabolism , Telomere Homeostasis , Telomere/metabolism , Transcription Factors/metabolism , Zinc Fingers , Cell Line, Tumor , DNA-Binding Proteins/genetics , Gene Knockout Techniques , Humans , Protein Binding , Tandem Repeat Sequences , Telomere/genetics , Telomeric Repeat Binding Protein 1/metabolism , Telomeric Repeat Binding Protein 2/metabolism , Transcription Factors/geneticsABSTRACT
BACKGROUND: The purpose was to determine if brain damage in Wilson's disease (WD) is different in comorbid bipolar spectrum disorders (BDs), comorbid major depressive disorder (MDD) or without any mood disorders. METHODS: An observational study was conducted on consecutive patients from a center for WD care. The study sample was divided by psychiatric assessment into WD without any mood disorders, WD with BDs and WD with MDD negative at Mood Disorder Questionnaire (MDQ). RESULTS: Thirty-eight WD patients were recruited (53.2% females): 21 without mood disorders (55.2%), 9 with comorbid BDs (26.7%) and 8 with MDD without MDQ+ (21.1%). The BDs showed a higher frequency of brain damage, reaching statistically significant differences in the basal ganglia (P<.001), in the overall brain (P<.003) and at the limit in the white matter (P<.05). CONCLUSIONS: In WD, comorbidity with BDs is associated with earlier evidence of brain damage, especially in the basal ganglia. The results confirm the importance of screening and early diagnosis of BDs in WD. Future follow-up studies on large samples are required to confirm if detection of BDs may be an early marker of brain damage and if a good therapeutic response in BDs may improve the prognosis of WD.
Subject(s)
Basal Ganglia/pathology , Bipolar Disorder/pathology , Depressive Disorder, Major/pathology , Hepatolenticular Degeneration/pathology , Magnetic Resonance Imaging/methods , White Matter/pathology , Adult , Bipolar Disorder/epidemiology , Comorbidity , Depressive Disorder, Major/epidemiology , Female , Hepatolenticular Degeneration/epidemiology , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Smoking behaviour and its course is influenced by personality factors. Affective temperaments could allow a more specific framework of the role trait affectivity plays in this seriously harmful health-behaviour. The aim of our study was to investigate if such an association exists in an ageing population with a special emphasis on gender differences. METHODS: 459 primary care patients completed the TEMPS-A, Beck Depression Inventory (BDI) and Hamilton Anxiety Rating Scale (HAM-A). Subjects were characterized according to their smoking behaviour as current, former or never smokers. Univariate analysis ANOVA and logistic regression were performed to analyse differences in the three smoking subgroups to predict smoking initiation and maintenance. RESULTS: Current smokers were younger and less educated than former or never smokers. Males were more likely to try tobacco during their lifetime and were more successful in cessation. Depressive, cyclothymic and irritable temperament scores showed significant differences between the three smoking subgroups. Irritable temperament was a predictor of smoking initiation in females whereas depressive temperament predicted smoking maintenance in males with a small, opposite effect of HAM-A scores independent of age, education, lifetime depression and BDI scores. Whereas smoking initiation was exclusively predicted by a higher BDI score in males, smoking maintenance was predicted by younger age and lower education in females. LIMITATIONS: The cross-sectional nature of the study design may lead to selective survival bias and hinder drawing causal relationships. CONCLUSIONS: Affective temperaments contribute to smoking initiation and maintenance independently of age, education, and depression. The significant contribution of depressive temperament in males and irritable temperament in females may highlight the role of gender-discordant temperaments in vulnerable subgroups.
