Teaching the Applications of CRISPR/Cas9: Using the African Turquoise Killifish as a Novel Model of Aging and Age-Related Diseases.

The development of genome editing technologies, including the novel CRISPR/Cas9 technique, has advanced scientific research concerning the contribution of genetics to disease through the creation of new model organisms. The subject of this review is a 2015 study done by Harel et al. from the journal Cell. This study is a prime example of using CRISPR/Cas9 to create a new model organism to accurately model the effects of aging and age-related diseases on a short-lived vertebrate. This study found that the African turquoise killifish is a reliable model to study the physiological process of aging due to its compressed lifespan. In addition, it provides a genotype-to-phenotype platform to study genes related to the hallmarks of aging and age-related diseases. This paper demonstrates this by showing that killifish deficient in the protein subunit of telomerase display telomerase-related pathologies faster than other established vertebrate models. From a teaching perspective, this paper could be used as a resource for educators to teach students about new technologies emerging in the field of neuroscience and the importance of model organisms. Specifically, for upper-level undergraduate students, this paper could serve as a real-world example of how scientific techniques such as CRISPR/Cas9 could be used to answer scientific questions. Further, it shows how these techniques could bring forward new model organisms better suited to answer the scientific questions being asked. Learning these techniques and being open minded to new approaches will be advantageous to students' future careers in science.

Psychosocial factors impacting community-based pressure ulcer prevention: A systematic review.

BACKGROUND: Pressure ulcers are a major health concern. They have a significant impact on the healthcare system and individuals, reducing quality of life across several domains. In community settings, self-management behaviours are central to their prevention. However, adherence with pressure ulcer prevention guidelines remains low, with little evidence guiding the relationship between patients and healthcare professionals to establish a concordant partnership. OBJECTIVE: To synthesise evidence on factors contributing to community-based pressure ulcer prevention using the Theoretical Domains Framework and the Capability, Opportunity, Motivation, Behaviour (COM-B) model of behaviour. DESIGN: Mixed methods systematic review and narrative synthesis. METHOD: Systematic searches were conducted in the CINAHL, Cochrane, EMBASE, PsycINFO, PubMed, Scopus, and Web of Science databases on 14th December 2022. Studies were eligible if they contained data on the factors associated with adherence and concordance with pressure ulcer prevention guidelines in the community for patients, caregivers, and healthcare professionals. Methodological quality was assessed using the Hawker tool. Findings were synthesised using the Theoretical Domains Framework. The resulting themes were mapped onto the Capability, Opportunity, Motivation, Behaviour (COM-B) model. RESULTS: Thirty studies were included in the review, including quantitative, qualitative, and mixed methods research. The synthesis identified 12 of the 14 Theoretical Domains Framework domains, with knowledge, social influences, beliefs about consequences, and beliefs about capabilities the most prevalent. Although knowledge appears to be an important contributor to adherence with prevention guidelines, knowledge alone does not appear sufficient to achieve concordance. A concordant relationship was facilitated by healthcare professionals' knowledge, motivation to work alongside patients and their priorities, and interpersonal skills to build rapport and trust, whilst barriers included lack of healthcare professional skills to navigate sensitive issues, paternalistic views of patient compliance and organisational processes that impact building rapport. CONCLUSIONS: Several psychosocial factors may affect the ability to achieve concordance between individuals, caregivers and healthcare professionals with pressure ulcer prevention guidelines in the community. However, data regarding the efficacy of behaviour change interventions targeting these constructs is limited, with further research required to guide intervention development in this area.

Structural features and ligand binding properties of tandem WW domains from YAP and TAZ, nuclear effectors of the Hippo pathway.

The paralogous multifunctional adaptor proteins YAP and TAZ are the nuclear effectors of the Hippo pathway, a central mechanism of organ size control and stem cell self-renewal. WW domains, mediators of protein-protein interactions, are essential for YAP and TAZ function, enabling interactions with PPxY motifs of numerous partner proteins. YAP has single and double WW domain isoforms (YAP1 and YAP2) whereas only a single WW domain isoform of TAZ has been described to date. Here we identify the first example of a double WW domain isoform of TAZ. Using NMR, we have characterized conformational features and peptide binding of YAP and TAZ tandem WW domains (WW1-WW2). The solution structure of YAP WW2 confirms that it has a canonical three-stranded antiparallel ß-sheet WW domain fold. While chemical shift-based analysis indicates that the WW domains in the tandem WW pairs retain the characteristic WW domain fold, 15N relaxation data show that, within the respective WW pairs, YAP WW1 and both WW1 and WW2 of TAZ undergo conformational exchange. 15N relaxation data also indicate that the linker between the WW domains is flexible in both YAP and TAZ. Within both YAP and TAZ tandem WW pairs, WW1 and WW2 bind single PPxY-containing peptide ligand concurrently and noncooperatively with sub-mM affinity. YAP and TAZ WW1-WW2 bind a dual PPxY-containing peptide with approximately 6-fold higher affinity. Our results indicate that both WW domains in YAP and TAZ are functional and capable of enhanced affinity binding to multi-PPxY partner proteins such as LATS1, ErbB4, and AMOT.