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Early events in the reprogramming of fibroblasts to cardiac muscle cells are unclear. While various histone undergo modification and re-positioning, and these correlate with the activity of certain genes, it is unknown if these events are causal or happen in response to reprogramming. Histone modification and re-positioning would be expected to open up chromatin on lineage-specific genes and this can be ascertained by studying nucleosome architecture. We have recently developed a set of tools to identify significant changes in nucleosome architecture which we used to study skeletal muscle differentiation. In this report, we have applied these tools to understand nucleosome architectural changes during fibroblast to cardiac muscle reprogramming. We found that nucleosomes surrounding the transcription start sites of cardiac muscle genes induced during reprogramming were insensitive to reprogramming factors as well as to agents which enhance reprogramming efficacy. In contrast, significant changes in nucleosome architecture were observed distal to the transcription start site. These regions were associated with nucleosome build-up. In summary, investigations into nucleosome structure do not support the notion that fibroblasts to cardiac muscle cell reprogramming involves chromatin opening and suggests instead long-range effects such as breaking closed-loop inhibition. [ABSTRACT FROM AUTHOR]

The article discusses the need for a reimagined U.S. biomedical research enterprise to address evolving health challenges and ensure national health progress. Topics discussed include the development of a national strategic vision, the importance of coordinated funding, and the prioritization of health equity and social determinants of health in research.

Hypertension affects >1 billion people worldwide. Complications of hypertension include stroke, renal failure, cardiac hypertrophy, myocardial infarction, and cardiac failure. Despite the development of various antihypertensive drugs, the number of people with uncontrolled hypertension continues to rise. While the lack of compliance associated with frequent side effects to medication is a contributory issue, there has been a failure to consider the diverse nature of hypertensive populations. Instead, we propose that hypertension can only be truly managed by precision. A precision medicine approach would consider each patient's unique factors. In this review, we discuss the progress toward precision medicine for hypertension with more predictiveness and individualization of treatment. We will highlight the advances in data science, omics (genomics, metabolomics, proteomics, etc), artificial intelligence, gene therapy, and gene editing and their application to precision hypertension. [ABSTRACT FROM AUTHOR]

The rapid and unprecedented climate changes driven by human-induced greenhouse gas emissions present a critical challenge for society today. However, the link between climate change and health remains inadequately explored in both literature and policy discussions. Thousands of individuals die each year in the United States due to climate-related factors, including extreme temperatures, severe weather, air pollution, and vector-borne diseases, and these health impacts disproportionately affect already vulnerable populations. Climate change is not just an environmental concern but also an imminent threat to individual and population health, as well as a major challenge to health equity. Moreover, the health sector significantly contributes to greenhouse gas emissions. Recognizing their roles as health care providers and contributors to the climate crisis, clinicians and health professionals have a moral obligation to emphasize the profound significance of climate impacts on human health and equity. This lecture provides an overview of efforts by the U.S. National Academy of Medicine and others to address the intersection of climate change and health, with an aim to raise awareness about the immediate threats to patient health and to build a proactive path forward for the health sector. The health sector must unite to collectively tackle these challenges, safeguard patient well-being, and promote the common good in the face of climate-induced health crises. [ABSTRACT FROM AUTHOR]

The article discusses the challenge of translating clinical research into health policy and the importance of finding high-quality evidence for medical decision-making. Topics discussed include the role of clinical trials, the National Academy of Medicine's involvement in providing unbiased policy advice, and the launch of a new series aimed at translating complex health policy issues into accessible articles for a broad audience.

We discovered that innate immunity plays an important role in the reprogramming of fibroblasts into cardiomyocytes. In this report, we define the role of a novel retinoic acid-inducible gene 1 Yin Yang 1 (Rig1:YY1) pathway. We found that fibroblast to cardiomyocyte reprogramming efficacy was enhanced by specific Rig1 activators. To understand the mechanism of action, we performed various transcriptomic, nucleosome occupancy, and epigenomic approaches. Analysis of the datasets indicated that Rig1 agonists had no effect on reprogramming-induced changes in nucleosome occupancy or loss of inhibitory epigenetic motifs. Instead, Rig1 agonists were found to modulate cardiac reprogramming by promoting the binding of YY1 specifically to cardiac genes. To conclude, these results show that the Rig1:YY1 pathway plays a critical role in fibroblast to cardiomyocyte reprogramming. [ABSTRACT FROM AUTHOR]