Endocardial HDAC3 is required for myocardial trabeculation.

Failure of proper ventricular trabeculation is often associated with congenital heart disease. Support from endocardial cells, including the secretion of extracellular matrix and growth factors is critical for trabeculation. However, it is poorly understood how the secretion of extracellular matrix and growth factors is initiated and regulated by endocardial cells. We find that genetic knockout of histone deacetylase 3 in the endocardium in mice results in early embryo lethality and ventricular hypotrabeculation. Single cell RNA sequencing identifies significant downregulation of extracellular matrix components in histone deacetylase 3 knockout endocardial cells. Secretome from cultured histone deacetylase 3 knockout mouse cardiac endothelial cells lacks transforming growth factor ß3 and shows significantly reduced capacity in stimulating cultured cardiomyocyte proliferation, which is remarkably rescued by transforming growth factor ß3 supplementation. Mechanistically, we identify that histone deacetylase 3 knockout induces transforming growth factor ß3 expression through repressing microRNA-129-5p. Our findings provide insights into the pathogenesis of congenital heart disease and conceptual strategies to promote myocardial regeneration.

Endocardial HDAC3 is required for myocardial trabeculation.

BACKGROUND: Trabeculation, a key process in early heart development, is the formation of myocardial trabecular meshwork. The failure of trabeculation often leads to embryonic lethality. Support from endocardial cells, including the secretion of extracellular matrix (ECM) and growth factors is critical for trabeculation; however, it is unknown how the secretion of ECM and growth factors is initiated and regulated by endocardial cells. METHODS: Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of histone deacetylase 3 (HDAC3) in the developing endocardium. RESULTS: We found that genetic deletion of Hdac3 in endocardial cells in mice resulted in early embryo lethality presenting as a hypotrabeculation cardiac phenotype. Single cell RNA sequencing identified several ECM components including collagens that were significantly downregulated in Hdac3 knockout (KO) endocardial cells. When cultured with supernatant from Hdac3 KO mouse cardiac endothelial cells (MCECs), wild-type mouse embryonic cardiomyocytes showed decreased proliferation, suggesting that growth signaling from Hdac3 KO MCECs is disrupted. Subsequent transcriptomic analysis revealed that transforming growth factor ß3 (TGFß3) was significantly downregulated in Hdac3 KO MCECs and Hdac3 cardiac endothelial KO hearts. Mechanistically, we identified that microRNA (miR)-129-5p was significantly upregulated in Hdac3 KO MCECs and Hdac3 cardiac endothelial KO hearts. Overexpression of miR-129-5p repressed Tgfß3 expression in wild-type MCECs, whereas knockdown of miR-129-5p restored Tgfß3 expression in Hdac3 KO MCECs. CONCLUSION: Our findings reveal a critical signaling pathway in which endocardial HDAC3 promotes trabecular myocardium growth by stimulating TGFß signaling through repressing miR-129-5p, providing novel insights into the etiology of congenital heart disease and conceptual strategies to promote myocardial regeneration.

Online micro intervention for mood improvement: The role of confidence, motivation, and activity type.

BACKGROUND: Internet interventions provide a unique opportunity to increase widespread accessibility of treatment at reduced and scalable costs (Muñoz, 2010). Previous research has explored the impact of specific types of activities on participant's main depressive symptoms i.e., anhedonia, or enjoyment levels, and mood (Bunge et al., 2017).The aim of the current study is to improve the understanding of the effects of online micro interventions targeting motivation, enjoyment levels, and mood. METHODS: A total of 838 participants recruited from Amazon Mechanical Turk participated in an online calendar activity to improve mood. RESULTS: A regression analysis showed that confidence and motivation were significantly associated with mood (R2 = 0.467, p < .001). The total number of activities reported in the last two days was associated with participants' current mood (R2 = 0.203, p < .001) and enjoyment (R2 = 0.156, p < .001). Interestingly, only mastery and meaningful activities improved mood but not pleasant activities. Regarding enjoyment, pleasant and meaningful activities impacted current enjoyment of the day but not mastery activities. Lastly, only individuals who engaged with the calendar showed a significant increase in motivation and confidence. LIMITATIONS: Depression may moderate engagement and was not analyzed in the present study. Additionally, there were no follow-up analyses that looked at the long-term effects of the intervention or changes in actual activity engagement. CONCLUSIONS: Online micro interventions have a promising future as an intervention that can impact the mood and motivation for change. Future studies should examine increasing engagement to facilitate confidence and motivation to enact change.

Psychometric Properties of a Chatbot Version of the PHQ-9 With Adults and Older Adults.

Background: The Patient Health Questionnaire-9 (PHQ-9) is a brief depression measure that has been validated. A chatbot version of the PHQ-9 would allow the assessment of depressive symptoms remotely, at a large scale and low cost. Objective: The current study aims to: Assess the feasibility of administering the PHQ-9 in a sample of adults and older adults via chatbot, report the psychometric properties of and identify the relationship between demographic variables and PHQ-9 total scores. Methods: A sample of 3,902 adults and older adults in the US and Canada were recruited through Facebook from August 2019 to February 2020 to complete the PHQ-9 using a chatbot. Results: A total of 3,895 (99.82%) completed the PHQ-9 successfully. The internal consistency of the PHQ-9 was 0.896 (p < 0.05). A one factor structure was found to have good model fit [X 2 (27, N = 1,948) = 365.396, p < 0.001; RMSEA = 0.080 (90% CI: 0.073, 0.088); CFI and TLI were 0.925 and 0.900, respectively, and SRMR was 0.039]. All of the demographic characteristics in this study were found to significantly predict PHQ-9 total score, however; their effect was negligible to weak. Conclusions: There was a large sample of adults and older adults were open to completing assessments via chatbot including those over 75. The psychometric properties of the chatbot version of the PHQ-9 provide initial support to the utilization of this assessment method.

Correction to: Characterization of polymorphic loci for two cicada species: Cryptotympana atrata and Hyalessa fuscata (Hemiptera: Cicadidae).

Unfortunately the title of the original publication contains a typo. Instead of (Hemiptera: Cicadoidae) it should be (Hemiptera: Cicadidae).

Characterization of polymorphic loci for two cicada species: Cryptotympana atrata and Hyalessa fuscata (Hemiptera: Cicadoidae).

The cicada species Cryptotympana atrata and Hyalessa fuscata are abundant in metropolitan Seoul where their population densities are positively correlated with local urban heat island intensities. Here, we characterized two panels of polymorphic markers for both species. A set of 21 microsatellite markers previously developed for a Chinese population of C. atrata were tested for the Korean population. Fifteen of the tested loci were found to be polymorphic in the target population. The number of alleles per locus ranged from 2 to 12, with observed and expected heterozygosities ranging from 0.2 to 1 and 0.06667 to 0.92644, respectively. Four of the tested loci were moderately polymorphic, and the rest were highly polymorphic. For H. fuscata, a novel panel of microsatellite markers was generated using a next-generation sequencing technique and 18 polymorphic loci were identified in the target population. The number of alleles per locus was between 3 and 16, with observed and expected heterozygosities ranging from 0.02222 to 0.97778 and 0.16804 to 0.86181, respectively. Polymorphism level was low in one locus, moderate in five loci, and high in the remaining loci. The microsatellite markers described in this study will be useful for identifying genetic structure and genetic differentiation among populations of C. atrata and H. fuscata in metropolitan Seoul.