Implementing community-based participatory research among African Americans with serious and persistent mental illness: A qualitative study

Community-based participatory research (CBPR) is an approach that involves community members in research, not as research participants, but as partners. However, few studies have examined CBPR projects conducted among African Americans with serious and persistent mental illness (SPMI). This article focuses specifically on the Inspiring Change (IC) model, which includes a leadership trio comprised of an academic researcher, health service provider and an African American with lived experience of SPMI. Our purpose is to investigate how the IC model shapes not only how research is conducted but how research is understood and experienced by the community. We achieve this purpose by (1) describing an innovative CBPR model and pilot projects that involved African Americans with SPMI in all stages of the research project; and (2) presenting findings from qualitative interviews conducted with CBPR team members about strengths, challenges and leadership particular to this model of CBPR, an area rarely explored in CBPR literature. With the guidance of an advisory board and the manualised IC curriculum, two CBPR teams initiated and conducted nine-month long research projects focusing on health disparities for African Americans with SPMI. Members of the two CBPR teams (n = 13), which included individuals with lived experience, service providers and researchers, completed qualitative interviews. Benefits of CBPR projects included opportunities to learn, a sense of purpose in helping others and increased trust of research participants. Challenges pertained to disorganisation of leadership, lack of transparency with compensation, time pressures and interpersonal conflicts. These challenges highlight the importance of preparing and supporting those from both academic and lived experience backgrounds in skills necessary to thrive in leadership roles for CBPR projects. &nbsp

Cre activity in fetal albCre mouse hepatocytes: Utility for developmental studies

The albCre transgene, having Cre recombinase driven by the serum albumin (alb) gene promoter, is commonly used to generate adult mice having reliable hepatocyte-specific recombination of loxP-flanked ("floxed") alleles. Based on previous studies, it has been unclear whether albCre transgenes are also reliable in fetal and juvenile mice. Perinatal liver undergoes a dynamic transition from being predominantly hematopoietic to predominantly hepatic. We evaluated Cre activity during this transition in albCre mice using a sensitive two-color fluorescent reporter system. From fetal through adult stages, in situ patterns of Cre-dependent recombination of the reporter closely matched expression of endogenous Alb mRNA or protein, indicating most or all hepatocytes, including those in fetal and juvenile livers, had expressed Cre and recombined the reporter. Our results indicate the albCre transgene is effective in converting simple floxed alleles in fetal and neonatal mice and is an appropriate tool for studies on hepatocyte development

Hepatocytes lacking thioredoxin reductase 1 have normal replicative potential during development and regeneration

Cells require ribonucleotide reductase (RNR) activity for DNA replication. In bacteria, electrons can flow from NADPH to RNR by either a thioredoxin-reductase- or a glutathione-reductase-dependent route. Yeast and plants artificially lacking thioredoxin reductases exhibit a slow-growth phenotype, suggesting glutathione-reductase-dependent routes are poor at supporting DNA replication in these organisms. We have studied proliferation of thioredoxin-reductase-1 (Txnrd1)-deficient hepatocytes in mice. During development and regeneration, normal mice and mice having Txnrd1-deficient hepatocytes exhibited similar liver growth rates. Proportions of hepatocytes that immunostained for PCNA, phosphohistone H3 or incorporated BrdU were also similar, indicating livers of either genotype had similar levels of proliferative, S and M phase hepatocytes, respectively. Replication was blocked by hydroxyurea, confirming that RNR activity was required by Txnrd1-deficient hepatocytes. Regenerative thymidine incorporation was similar in normal and Txnrd1-deficient livers, further indicating that DNA synthesis was unaffected. Using genetic chimeras in which a fluorescently marked subset of hepatocytes was Txnrd1-deficient while others were not, we found that the multigenerational contributions of both hepatocyte types to development and to liver regeneration were indistinguishable. We conclude that, in mouse hepatocytes, a Txnrd1-independent route for the supply of electrons to RNR can fully support DNA replication and normal proliferative growth