Inhibition of the YAP-MMB interaction and targeting NEK2 as potential therapeutic strategies for YAP-driven cancers.

YAP activation in cancer is linked to poor outcomes, making it an attractive therapeutic target. Previous research focused on blocking the interaction of YAP with TEAD transcription factors. Here, we took a different approach by disrupting YAP's binding to the transcription factor B-MYB using MY-COMP, a fragment of B-MYB containing the YAP binding domain fused to a nuclear localization signal. MY-COMP induced cell cycle defects, nuclear abnormalities, and polyploidization. In an AKT and YAP-driven liver cancer model, MY-COMP significantly reduced liver tumorigenesis, highlighting the importance of the YAP-B-MYB interaction in tumor development. MY-COMP also perturbed the cell cycle progression of YAP-dependent uveal melanoma cells but not of YAP-independent cutaneous melanoma cell lines. It counteracted YAP-dependent expression of MMB-regulated cell cycle genes, explaining the observed effects. We also identified NIMA-related kinase (NEK2) as a downstream target of YAP and B-MYB, promoting YAP-driven transformation by facilitating centrosome clustering and inhibiting multipolar mitosis.

Profile of Athletes With a Vision Impairment: Exploring Demographics and Ocular Pathologies of Athletes in Three Paralympic Sports.

OBJECTIVE: This study aimed to explore the profile of athletes with a vision impairment who compete in three Paralympic sports (goalball, vision impairment judo, and blind football). DESIGN: Descriptive and association analyses of the vision impairment athletes' profile were conducted. RESULTS: The typical athlete profile was a male (65.1%), aged 26-34 yrs (39.7%), from Europe (38.8%), representing a country with a high income (46.1%), and was diagnosed with a retinal-related ocular pathology (38.9%). In all three sports, the ages of the athletes were similar. In goalball, most athletes were from Europe, represented countries with a high income, and were diagnosed with retinal-, globe-, or neurological-related pathologies. In vision impairment judo, the majority of athletes were from Asia, represented countries with an upper middle income, and were diagnosed with retinal-, global-, or neurological-related pathologies. In blind football, most athletes were from Europe, represented countries with an upper middle income, and were diagnosed with retinal-, neurological-related ocular pathologies, or glaucoma. CONCLUSIONS: The homogeneity of the athletes' profile suggests that an effort is needed to target other parts of the vision impairment population to take part in vision impairment sports. Differences in the athletes' profiles across the sports provide information that may be useful for sport-specific talent identification.

Impact of Running With and Without a Guide on Short Distance Running Performance for Athletes With a Vision Impairment.

OBJECTIVE: This study aimed to investigate the difference of running with or without a guide on running performance (100, 200, and 400 m) for athletes with a vision impairment. DESIGN: Data including athletes' and guides' sex, age, and race times were extracted from 11 elite competitions. RESULTS: Male athletes predominantly ran without a guide (100 m = 91.4%, 200 m = 88.1%, 400 m = 84.8%), whereas female athletes mainly ran with a guide (100 m = 60.5%, 200 m = 80.0%, 400 m = 72.0%). No significant difference in 100-m race times was found between male athletes with or without a guide ( P = 0.647). For the 200 m ( P = 0.001) and 400 m ( P = 0.030), race times were significantly slower for male athletes running with a guide (mean rank 200 m = 36.80, 400 m = 33.57) compared to without a guide (mean rank 200 m = 19.43, 400 m = 21.69). Conversely, 100- ( P = 0.015), 200- ( P = 0.025), and 400-m ( P = 0.029) race times were significantly faster for female athletes with (mean rank 100 m = 18.25, 200 m = 13.71, 400 m = 11.00) compared with without a guide (mean rank 100 m = 27.74, 200 m = 22.67, 400 m = 21.69). CONCLUSIONS: Running with a guide affects vision impairment athletes' race times. The influence of running with a guide, and the gender mix of vision impairment athlete and guide, should be considered in any research with the aim of establishing a new classification system for vision impairment athletes.

Evidence-based Classification in Track Athletics for Athletes with a Vision Impairment: A Delphi Study.

SIGNIFICANCE: The Delphi analysis presented here highlights the need for a sport-specific evidence-based classification system for track athletics for athletes with a vision impairment (VI). This system may differ for different race distances. Further research is required to develop a useful test battery of vision tests for classification. The issue of intentional misrepresentation during classification needs particular attention. PURPOSE: At present, athletes with VI are placed into competition classes developed on the basis of legal definitions of VI. The International Paralympic Committee Athlete Classification Code states that all sports should have their own classification system designed to reflect the (visual) demands of that individual sport. This project gathered expert opinion on the specific requirements for an evidence-based sport-specific classification system for VI track athletics and to identify any particular issues within track athletics that require further research into their impact on sport performance. METHODS: A three-round Delphi review was conducted with a panel of 17 people with expertise in VI track athletics. RESULTS: The panel agreed that the current classification system in VI track athletics does not completely minimize the impact of impairment on competition outcome, highlighting the need for improvements. There was clear agreement that the existing measures of vision may fail to adequately reflect the type of vision loss that would impact running performance, with additional measures required. Intentional misrepresentation, where athletes "cheat" on classification tests, remains a serious concern. CONCLUSIONS: The panel has identified measures of vision and performance that will inform the development of an evidence-based classification system by better understanding the relationship between VI and performance in track athletics. Issues such as the use of guides and whether the current class system was equitable gave rise to differing opinions within the panel, with these varying across the different running distances.