Nucleolar organization, ribosomal DNA array stability, and acrocentric chromosome integrity are linked to telomere function.

The short arms of the ten acrocentric human chromosomes share several repetitive DNAs, including ribosomal RNA genes (rDNA). The rDNA arrays correspond to nucleolar organizing regions that coalesce each cell cycle to form the nucleolus. Telomere disruption by expressing a mutant version of telomere binding protein TRF2 (dnTRF2) causes non-random acrocentric fusions, as well as large-scale nucleolar defects. The mechanisms responsible for acrocentric chromosome sensitivity to dysfunctional telomeres are unclear. In this study, we show that TRF2 normally associates with the nucleolus and rDNA. However, when telomeres are crippled by dnTRF2 or RNAi knockdown of TRF2, gross nucleolar and chromosomal changes occur. We used the controllable dnTRF2 system to precisely dissect the timing and progression of nucleolar and chromosomal instability induced by telomere dysfunction, demonstrating that nucleolar changes precede the DNA damage and morphological changes that occur at acrocentric short arms. The rDNA repeat arrays on the short arms decondense, and are coated by RNA polymerase I transcription binding factor UBF, physically linking acrocentrics to one another as they become fusogenic. These results highlight the importance of telomere function in nucleolar stability and structural integrity of acrocentric chromosomes, particularly the rDNA arrays. Telomeric stress is widely accepted to cause DNA damage at chromosome ends, but our findings suggest that it also disrupts chromosome structure beyond the telomere region, specifically within the rDNA arrays located on acrocentric chromosomes. These results have relevance for Robertsonian translocation formation in humans and mechanisms by which acrocentric-acrocentric fusions are promoted by DNA damage and repair

Measures of behavioral function predict duration of video game play: utilization of the Video Game Functional Assessment - Revised

Background: Internet gaming disorder (IGD) was introduced in the DSM-5 as a way of identifying and diagnosing problematic video game play. However, the use of the diagnosis is constrained, as it shares criteria with other addictive orders (e.g., pathological gambling). Aims: Further work is required to better understand IGD. One potential avenue of investigation is IGD’s relationship to the primary reinforcing behavioral functions. This study explores the relationship between duration of video game play and the reinforcing behavioral functions that may motivate or maintain video gaming. Methods: A total of 499 video game players began the online survey, with complete data from 453 participants (85% white and 28% female), were analyzed. Individuals were placed into five groups based on self-reported hours of video gaming per week, and completed the Video Game Functional Assessment – Revised (VGFA-R). Results: The results demonstrated the escape and social attention function were significant in predicting duration of video game play, whereas sensory and tangible were not significant. Conclusion: Future implications of the VGFA-R and behaviorally based research are discussed