Promoting Cardiovascular Health in the Community: Training the Next Generation of Scientists in the Jackson Heart Study.

PURPOSE: The aim of this article is to show the impact of the use of National Institutes of Health (NIH) research supplements in the training of African American students affiliated with the Jackson Heart Study (JHS). RECENT FINDINGS: The JHS Undergraduate Training and Education Center (UTEC) at Tougaloo College has had 19 students to be awarded research supplements. The awardees gained invaluable skills while working on the research supplements. Additionally, research supplement awards inspired these students to not only consider working in health-related fields, but to continue to engage in research activities and to mentor.

Thinking Ahead to the Next Generation of Cardiometabolic Investigators: What It Takes to Successfully Engage Underrepresented Minorities in Biomedical and Public Health Careers.

PURPOSE OF REVIEW: The purpose of this review is to examine the existing information regarding cardiometabolic syndrome (CMS) manifestations among underrepresented minority populations, underrepresented minorities' representation in the cardiometabolic workforce, and the models that successfully recruit and retain underrepresented minorities in the field. RECENT FINDINGS: The scientific literature is replete with information on methods to recruit and train URM in research careers. However, there are few programs that are specifically designed to train URM to become diabetes researchers, or more specifically cardiometabolic researchers. The CMS scientific community leaders do not have to design a new learning program to engage URM in research. They only have to follow the prototypes by other organizations and make applicable to cardiometabolic research.

The search for a PKR code-differential regulation of protein kinase R activity by diverse RNA and protein regulators.

The interferon-inducible protein kinase R (PKR) is a key component of host innate immunity that restricts viral replication and propagation. As one of the four eIF2α kinases that sense diverse stresses and direct the integrated stress response (ISR) crucial for cell survival and proliferation, PKR's versatile roles extend well beyond antiviral defense. Targeted by numerous host and viral regulators made of RNA and proteins, PKR is subject to multiple layers of endogenous control and external manipulation, driving its rapid evolution. These versatile regulators include not only the canonical double-stranded RNA (dsRNA) that activates the kinase activity of PKR, but also highly structured viral, host, and artificial RNAs that exert a full spectrum of effects. In this review, we discuss our deepening understanding of the allosteric mechanism that connects the regulatory and effector domains of PKR, with an emphasis on diverse structured RNA regulators in comparison to their protein counterparts. Through this analysis, we conclude that much of the mechanistic details that underlie this RNA-regulated kinase await structural and functional elucidation, upon which we can then describe a "PKR code," a set of structural and chemical features of RNA that are both descriptive and predictive for their effects on PKR.

Cardiovascular Disease in African Americans: Innovative Community Engagement for Research Recruitment and Impact.

Historical events and the illumination of unequal treatment of cardiovascular and other diseases among African Americans and their white counterparts have suppressed African Americans' participation in research. Approaches that bring scientific professionals into actual partnership with affected communities show promise for overcoming this reluctance. Two examples are the Jackson Heart Study (JHS) and the emerging Moyo Health Network (MOYO). JHS uses layers of community engagement, including a pioneering effort to develop future health scientists and practitioners, the JHS Undergraduate Training and Education Center (UTEC). JHS-UTEC focuses on preparing young adults and teenagers (mostly African Americans) for rigorous higher-level learning and careers in health research and practice. MOYO is a mobile platform for health research to examine factors contributing to the development of disparities in the young while creating channels to disseminate interventions. Community trust in MOYO is substantially enhanced through its education and training program, which offers engaging ideation events along with app development and coding training opportunities to young people. Participants impart their cultural insights while using newly acquired technology skills to help with the community-focused design and launch of the network. The JHS and MOYO provide models for addressing cardiovascular health disparities by fostering community partnerships.

Capacity-Building for Career Paths in Public Health and Biomedical Research for Undergraduate Minority Students: A Jackson Heart Study Success Model.

OBJECTIVE: This article chronicles the building of individual student capacity as well as faculty and institutional capacity, within the context of a population-based, longitudinal study of African Americans and cardiovascular disease. The purpose of this article is to present preliminary data documenting the results of this approach. DESIGN: The JHS Scholars program is designed, under the organizational structure of the Natural Sciences Division at Tougaloo College, to provide solid preparation in quantitative skills through: good preparation in mathematics and the sciences; a high level of reading comprehension; hands-on learning experiences; and mentoring and counseling to sustain the motivation of the students to pursue further studies. SETTING: This program is on the campus of a private Historically Black College in Mississippi. PARTICIPANTS: The participants in the program are undergraduate students. MAIN OUTCOME MEASURES: Data, which included information on major area of study, institution attended, degrees earned and position in the workforce, were analyzed using STATA 14. RESULTS: Of 167 scholars, 46 are currently enrolled, while 118 have graduated. One half have completed graduate or professional programs, including; medicine, public health, pharmacy, nursing, and biomedical science; approximately one-fourth (25.4 %) are enrolled in graduate or professional programs; and nearly one tenth (9.3%) completed graduate degrees in law, education, business or English. CONCLUSIONS: These data could assist other institutions in understanding the career development process that helps underrepresented minority students in higher education to make career choices on a path toward public health, health professions, biomedical research, and related careers.

Living through their first pandemic: Mississippi young adults reveal COVID-19 concerns and challenges.

Objective: The study aimed to understand the perceptions, knowledge, information sources, and coping skills pertaining to COVID-19 among two groups of African American young adults. Participants: African American ages 18-29 years enrolled in Historically Black Colleges and Universities and non-college enrolled young adults in Mississippi were the participants. Methods: Focus groups were conducted from February through May 2021. The qualitative data were analyzed using thematic analysis. Results: Findings suggest the college students faced anxiety and stress from the loss of loved ones and the college experience. Non-college enrolled young adults dealt with maintaining employment, pros and cons of taking the vaccine to continue work, and handling the frequent flow of information. Conclusion: The study highlights the importance of ensuring that reliable and trustworthy health promotion and health crisis prevention information, resources, and coping tools are available in the environments in which young adults live, learn, and work.

Selective Detection of Misfolded Tau From Postmortem Alzheimer's Disease Brains.

Tau aggregates are present in multiple neurodegenerative diseases known as "tauopathies," including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, and corticobasal degeneration. Such misfolded tau aggregates are therefore potential sources for selective detection and biomarker discovery. Six human tau isoforms present in brain tissues and both 3R and 4R isoforms have been observed in the neuronal inclusions. To develop selective markers for AD and related rare tauopathies, we first used an engineered tau protein fragment 4RCF as the substrate for ultrasensitive real-time quaking-induced conversion analyses (RT-QuIC). We showed that misfolded tau from diseased AD and other tauopathy brains were able to seed recombinant 4RCF substrate. We further expanded to use six individual recombinant tau isoforms as substrates to amplify misfolded tau seeds from AD brains. We demonstrated, for the first time to our knowledge, that misfolded tau from the postmortem AD brain tissues was able to specifically seed all six full-length human tau isoforms. Our results demonstrated that RT-QuIC analysis can discriminate AD and other tauopathies from non-AD normal controls. We further uncovered that 3R-tau isoforms displayed significantly faster aggregation kinetics than their 4R-tau counterparts under conditions of both no seeding and seeding with AD brain homogenates. In summary, our work offers potential new avenues of misfolded tau detection as potential biomarkers for diagnosis of AD and related tauopathies and provides new insights into isoform-specific human tau aggregation.

Heterogeneity of cellular inflammatory responses in ageing white matter and relationship to Alzheimer's and small vessel disease pathologies.

White matter lesions (WML) are common in the ageing brain, often arising in a field effect of diffuse white matter abnormality. Although WML are associated with cerebral small vessel disease (SVD) and Alzheimer's disease (AD), their cause and pathogenesis remain unclear. The current study tested the hypothesis that different patterns of neuroinflammation are associated with SVD compared to AD neuropathology by assessing the immunoreactive profile of the microglial (CD68, IBA1 and MHC-II) and astrocyte (GFAP) markers in ageing parietal white matter (PARWM) obtained from the Cognitive Function and Ageing Study (CFAS), an ageing population-representative neuropathology cohort. Glial responses varied extensively across the PARWM with microglial markers significantly higher in the subventricular region compared to either the middle-zone (CD68 p = 0.028, IBA1 p < 0.001, MHC-II p < 0.001) or subcortical region (CD68 p = 0.002, IBA1 p < 0.001, MHC-II p < 0.001). Clasmatodendritic (CD) GFAP+ astrocytes significantly increased from the subcortical to the subventricular region (p < 0.001), whilst GFAP+ stellate astrocytes significantly decreased (p < 0.001). Cellular reactions could be grouped into two distinct patterns: an immune response associated with MHC-II/IBA1 expression and CD astrocytes; and a more innate response characterised by CD68 expression associated with WML. White matter neuroinflammation showed weak relationships to the measures of SVD, but not to the measures of AD neuropathology. In conclusion, glial responses vary extensively across the PARWM with diverse patterns of white matter neuroinflammation. Although these findings support a role for vascular factors in the pathogenesis of age-related white matter neuroinflammation, additional factors other than SVD and AD pathology may drive this. Understanding the heterogeneity in white matter neuroinflammation will be important for the therapeutic targeting of age-associated white matter damage.

The Jackson Heart Study: Preparing African American High School Students for Health Careers and Research.

In 1999, Tougaloo College (TC), located in Jackson, Mississippi, was charged, as a part of its role in the Jackson Heart Study (JHS), with creating a pool of well-trained high school students who, upon entering college, could successfully complete undergraduate and graduate or professional degrees in the health professions, biomedical research, and public health. TC identified the following educational challenges experienced by Mississippi high school students: inadequate exposure to reading, writing, logic, and quantitative skills; inadequate course work in science and mathematics; lack of mentors and role models in science-related fields as well as for exploration and identification of career options in the health professions and biomedical research. To this end, the JHS Undergraduate Training and Education Center (JHS UTEC) developed three four-week summer workshops in Science, Language Arts, and Mathematics (SLAM) for high school students in grades 9 through 11. Since SLAM's inception, more than 900 students have completed the program, and more than 90% have enrolled in college. In addition, according to National Student Clearinghouse and participant-reported data, many of the SLAM participants have earned not only undergraduate degrees in science, but also graduate degrees in a health-related and STEM fields. This article details the SLAM curricula and strategies for recruiting, selecting, training, and retaining high school students; we also present data to illustrate the success of the SLAM program.

The Role of Public Health Partnerships in the Success of the Jackson Heart Study Undergraduate Training and Education Center.

Background: The Jackson Heart Study (JHS) is a single-site prospective epidemiologic investigation of cardiovascular disease (CVD) among African Americans from the central Jackson, Mississippi area. The study is a collaboration between Jackson State University (JSU), University of Mississippi Medical Center (UMMC), Tougaloo College (TC), and the Mississippi State Department of Health (MSDH). The JHS Undergraduate Training and Education Center (JHSUTEC) at TC was developed to increase the numbers of college-aged African American students entering public health and health-related fields. To achieve this goal, the UTEC designed the Jackson Heart Study (JHS) Scholars program. Methods: JHS Scholars are required to take additional classes and participate in public health and/or biomedical research. The scholars engage in research locally during the academic year. However, many scholars participate in research outside of the Jackson Metropolitan area during the summer. Because of this, national collaborators were needed to act as mentors and hosts. Results: Since the inception of the JHSUTEC, more than 15 collaborations have been formed that have shared resources and student successes. As of May 2018, more than150 students have successfully completed the JHS Scholars program and many have continued into careers in public health, biomedical research, and medicine. Since 2004, JHS scholars have published 29 papers and 15 scholars have received diversity supplements. Conclusion: Collaborative activities and public health partnerships have contributed to the success of the JHSUTEC program and have served as a pathway of entry into STEM fields for minority students.

Crystal structure of an adenovirus virus-associated RNA.

Adenovirus Virus-Associated (VA) RNAs are the first discovered viral noncoding RNAs. By mimicking double-stranded RNAs (dsRNAs), the exceptionally abundant, multifunctional VA RNAs sabotage host machineries that sense, transport, process, or edit dsRNAs. How VA-I suppresses PKR activation despite its strong dsRNA character, and inhibits the crucial antiviral kinase to promote viral translation, remains largely unknown. Here, we report a 2.7 Å crystal structure of VA-I RNA. The acutely bent VA-I features an unusually structured apical loop, a wobble-enriched, coaxially stacked apical and tetra-stems necessary and sufficient for PKR inhibition, and a central domain pseudoknot that resembles codon-anticodon interactions and prevents PKR activation by VA-I. These global and local structural features collectively define VA-I as an archetypal PKR inhibitor made of RNA. The study provides molecular insights into how viruses circumnavigate cellular rules of self vs non-self RNAs to not only escape, but further compromise host innate immunity.

Structural basis of amino acid surveillance by higher-order tRNA-mRNA interactions.

Amino acid availability in Gram-positive bacteria is monitored by T-box riboswitches. T-boxes directly bind tRNAs, assess their aminoacylation state, and regulate the transcription or translation of downstream genes to maintain nutritional homeostasis. Here, we report cocrystal and cryo-EM structures of Geobacillus kaustophilus and Bacillus subtilis T-box-tRNA complexes, detailing their multivalent, exquisitely selective interactions. The T-box forms a U-shaped molecular vise that clamps the tRNA, captures its 3' end using an elaborate 'discriminator' structure, and interrogates its aminoacylation state using a steric filter fashioned from a wobble base pair. In the absence of aminoacylation, T-boxes clutch tRNAs and form a continuously stacked central spine, permitting transcriptional readthrough or translation initiation. A modeled aminoacyl disrupts tRNA-T-box stacking, severing the central spine and blocking gene expression. Our data establish a universal mechanism of amino acid sensing on tRNAs and gene regulation by T-box riboswitches and exemplify how higher-order RNA-RNA interactions achieve multivalency and specificity.

Natural product-based amyloid inhibitors.

Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned.

Factors Affecting Dietary Practices in a Mississippi African American Community.

This study examined the practices, personal motivation, and barriers of African American communities in Mississippi regarding their dietary practices. We selected the Metro Jackson Area comprised of Hinds, Madison and Rankin Counties because it is a combination of urban and rural communities. The sample consisted of 70 participants from seven sites. A total of seven focus groups responded to six questions to assess practices, personal motivation, and barriers to dietary practices: (1) Where in your community can you access fresh fruits and vegetables? (2) How many meals a day should a person eat? (3) What would you consider to be a healthy breakfast, lunch and dinner? (4) What would you consider to be a healthy snack? (5) What do you consider to be your motivations for eating healthy? (6) What do you consider to be your barriers to eating healthy? Each of the seven focus groups consisted of 6 to 12 participants and provided details of their dietary practices. The focus group interviews were digitally-recorded. The recorded interviews were transcribed. The majority of the participants stated that there is a limited availability of fresh fruits/vegetables in rural areas because of a shortage of grocery stores. When they do find fruits, they are priced very high and are unaffordable. Even though health conditions dictate food frequency and portion size, community members feel that individuals should eat three good balanced meals per day with snacks, and they should adhere to small portion sizes. While the desire to attain overall good health and eliminate associative risks for heart disease (e.g., diabetes, obesity) are personal motivations, the cost of food, transportation, age, and time required for food preparation were seen as barriers to healthy eating. Decisions regarding meal choice and meal frequency can have an impact on long-term health outcomes. Health promotion programs should become an integral part of academic- community collaborative agreements.

Perception of Policy and Environmental Action to Promote Healthy Behaviors in African American Communities.

The present study aimed to examine the perceptions of African American communities regarding the involvement of political leaders in facilitating policy and environmental change promoting healthy eating and physical activity. We selected the Metro Jackson Area comprised of Hinds, Madison and Rankin Counties because it is a combination of urban and rural communities. The sample consisted of 70 participants from seven sites. A total of seven focus groups were asked to respond to one question to assess political leaders' involvement in healthy living: "When you think about your political leaders that you have in the Jackson, Mississippi area, do any of them promote healthy eating and physical activity?" Focus groups consisted of six to 12 participants and were asked to comment on their participation in physical activity. The focus group interviews were digitally recorded. The recorded interviews were transcribed by a professional transcriptionist. Community members could not recollect much participation from political leaders in the health prevention/intervention efforts. In each of the counties, there was evidence that there was some involvement by local politicians in health promotion issues, but not on a large scale. In conclusion, making healthy foods and products available in neighborhood stores has long been associated with healthy behaviors and positive health outcomes. This can make a difference in the Mississippi communities where supermarkets are not accessible and health disparities abound.

Recruiting African-American research participation in the Jackson Heart Study: methods, response rates, and sample description.

OBJECTIVE: The sampling and recruitment methods, response rate, and cohort description for the all-African-American Jackson Heart Study (JHS) are detailed. METHODS: Four subsamples of participants residing in the Jackson, Mississippi metropolitan statistical area (MSA) were included: random, volunteer, ARIC (continuing from Atherosclerosis Risk in Communities study), and family. A community-driven recruitment model was developed, and community representatives guided recruitment. RESULTS: 96% (n=5,302) of target enrollment was achieved with diversity in sex, education, and income. The JHS cohort provides a sample of African-American adults for longitudinal investigation. DISCUSSION: Cohort recruitment was challenging. The JHS experiences provide useful lessons for observational epidemiological studies recruiting African-American research participation. Co-participation of researchers and researched in study design and realistic evidence of community benefit were crucial to recruitment success.

Racism and cardiovascular disease in African Americans.

This article provides an overview of the evidence on the ways racism can affect the disproportionate rates of cardiovascular disease (CVD) in African Americans. It describes the significant health disparities in CVD for blacks and whites and suggests that racial disparities should be understood within the context of persistent inequities in societal institutions and relations. Evidence and potential pathways for exploring effects of 3 levels of racism on cardiovascular health risk factors and outcomes are reviewed. First, institutional racism can lead to limited opportunities for socioeconomic mobility, differential access to goods and resources, and poor living conditions that can adversely affect cardiovascular health. Second, perceived/personally mediated racism acts as a stressor and can induce psychophysiological reactions that negatively affect cardiovascular health. Third, in race-conscious societies, such as the United States, the negative self-evaluations of accepting negative cultural stereotypes as true (internalized racism) can have deleterious effects on cardiovascular health. Few population-based studies have examined the relationship between racism and CVD. The findings, though suggestive of a positive association, are neither consistent nor clear. The research agenda of the Jackson Heart Study in addressing the role of racism in CVD is presented.

A community-driven model of research participation: the Jackson Heart Study Participant Recruitment and Retention Study.

Recruiting African Americans for research participation is a recognized challenge. The aim of the Jackson Heart Study (JHS) is to recruit and retain 6,500 African-American participants to examine the risk factors and causes of heart disease in this ethnic group. A multi-method Participant Recruitment and Retention Study was conducted prior to initiating the JHS as a basis for designing a culture-specific plan for recruitment, retention, and adherence of participants. Probability and purposive sampling were used to select African-American adults aged 35-84 from the Jackson area. Data were collected using a structured survey (N=125) and in-depth interviews (N=31 individual; 10 group). Data were analyzed and interpreted using inferential statistics and interpretive phenomenology to identify participatory barriers and facilitators, and to uncover the meaning of taking part in research. Findings generated an emerging Community-Driven Model, which has potential to enlighten researchers about effective strategies for recruiting and retaining African Americans for research participation.