Heart disease is the leading cause of mortality and morbidity in the western world. The heart has little regenerative capacity after damage, leading to much interest in understanding the factors ...required to produce new cardiac myocytes. Despite a robust understanding of the molecular networks regulating cardiac differentiation, no single transcription factor or combination of factors has been shown to activate the cardiac gene program de novo in mammalian cells or tissues. Here we define the minimal requirements for transdifferentiation of mouse mesoderm to cardiac myocytes. We show that two cardiac transcription factors, Gata4 and Tbx5, and a cardiac-specific subunit of BAF chromatin-remodelling complexes, Baf60c (also called Smarcd3), can direct ectopic differentiation of mouse mesoderm into beating cardiomyocytes, including the normally non-cardiogenic posterior mesoderm and the extraembryonic mesoderm of the amnion. Gata4 with Baf60c initiated ectopic cardiac gene expression. Addition of Tbx5 allowed differentiation into contracting cardiomyocytes and repression of non-cardiac mesodermal genes. Baf60c was essential for the ectopic cardiogenic activity of Gata4 and Tbx5, partly by permitting binding of Gata4 to cardiac genes, indicating a novel instructive role for BAF complexes in tissue-specific regulation. The combined function of these factors establishes a robust mechanism for controlling cellular differentiation, and may allow reprogramming of new cardiomyocytes for regenerative purposes.
The coronavirus disease 2019 (COVID-19) pandemic has led to economic contraction and significant restrictions on society. The shock to the economy could lead to a deterioration of physical health ...outcomes, including dental health. The present study investigated the association between worsened socioeconomic conditions due to the COVID-19 pandemic and dental pain in Japan. The mediating effects of psychological distress and oral health–related behaviors were also evaluated. Cross-sectional data from the Japan COVID-19 and Society Internet Survey conducted from August to September 2020 (n = 25,482; age range, 15–79 y) were analyzed. Multivariable logistic regression models were fitted to evaluate the independent associations of household income reduction, work reduction, and job loss due to the COVID-19 pandemic with dental pain within a month. Dental pain was reported by 9.8%. Household income reduction, work reduction, and job loss were independently associated with dental pain after adjusting for confounders (odds ratios: 1.42 95% confidence interval (CI), 1.28−1.57, 1.58 95% CI, 1.41−1.76, 2.17 95% CI, 1.64−2.88, respectively). The association related to household income reduction was mediated by psychological distress, postponing dental visits, toothbrushing behavior, and between-meals eating behavior by 21.3% (95% CI, 14.0−31.6), 12.4% (95% CI, 7.2−19.6), 1.5% (95% CI, −0.01 to 4.5), and 9.3% (95% CI, 5.4−15.2), respectively. Our findings showed that worsened socioeconomic conditions due to the COVID-19 pandemic deteriorated dental health. Policies that protect income and job loss may reduce dental health problems after the pandemic.
We provide numerical evidence that a finite-dimensional inertial manifold on which the dynamics of a chaotic dissipative dynamical system lives can be constructed solely from the knowledge of a set ...of unstable periodic orbits. In particular, we determine the dimension of the inertial manifold for the Kuramoto-Sivashinsky system and find it to be equal to the "physical dimension" computed previously via the hyperbolicity properties of covariant Lyapunov vectors.
Tooth loss is a risk factor for increased mortality; however, the underlying mechanism remains unclear. This study aimed to evaluate the mediating effect of weight change on the relationship between ...tooth loss and mortality risk. This was a 10-y follow-up prospective cohort study using the data from the Japan Gerontological Evaluation Study (JAGES). The participants were independent older adults aged ≥65 y at baseline and were followed up from 2010 to 2020. The incidence of death in 2013 and 2020, incidence of >5% weight loss/gain in 2010 and 2013, and the number of remaining teeth in 2010 were used as the outcome, mediator, and explanatory variables, respectively. We conducted causal mediation analysis by fitting the Cox proportional hazard model, including possible confounders. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the total effect (TE), natural indirect effect (NIE), and proportion mediated (PM) were estimated. Among the 34,510 participants, the mean age was 72.6 (SD = 5.4) y, and 47.6% were men. From 2013 to 2020, 14.0% of the participants (n = 4,825) died, 60.5% (n = 20,871) had 0 to 19 remaining teeth, and 17.2% (n = 5,927) and 8.4% (n = 2,907) experienced >5% weight loss and gain, respectively. The mortality rate was 0.016 per person-year among those with ≥20 remaining teeth and 0.027 per person-year among those with 0 to 19 remaining teeth. Weight loss of >5% significantly mediated the association between tooth loss and higher mortality risk (TE: HR, 1.28 95% CI, 1.16 to 1.40; NIE: HR, 1.03 95% CI, 1.02 to 1.04; PM, 13.1%); however, we observed a slight mediating effect for >5% weight gain (NIE: HR, 1.003 95%CI, 1.0001 to 1.01; PM, 1.3%). The present study suggests that a clinically meaningful level of weight loss mediated the association between tooth loss and increased risk of mortality among independent older adults.
Glypican-5 (GPC5) is a heparan sulfate proteoglycan (HSPG) localized to the plasma membrane. We previously reported that in the human mesenchymal stem cell line UE6E7T-3, GPC5 is overexpressed in ...association with transformation and promotes cell proliferation by acting as a co-receptor for Sonic hedgehog signaling. In this study, we found using immunofluorescence microscopy that in transformed cells (U3DT), GPC5 localized not only at primary cilia on the cell surface, but also at the leading edge of migrating cells, at the intercellular bridge and blebs during cytokinesis, and in extracellular vesicles. In each subcellular region, GPC5 colocalized with fibroblast growth factor receptor (FGFR) and the small GTPases Rab11 and ARF6, indicating that GPC5 is delivered to these regions by Rab11-associated recycling endosomes. These colocalizations suggest that GPC5 plays an important role in FGF2 stimulation of cell migration, which was abrogated by knockdown of GPC5. Our findings indicate that GPC5 plays a role in regulation of U3DT cell migration and provides several insights into the functions of GPC5 that could be elucidated by future studies.
Human mutations in TBX5, a gene encoding a T-box transcription factor, and SALL4, a gene encoding a zinc-finger transcription factor, cause similar upper limb and heart defects. Here we show that ...Tbx5 regulates Sall4 expression in the developing mouse forelimb and heart; mice heterozygous for a gene trap allele of Sall4 show limb and heart defects that model human disease. Tbx5 and Sall4 interact both positively and negatively to finely regulate patterning and morphogenesis of the anterior forelimb and heart. Thus, a positive and negative feed-forward circuit between Tbx5 and Sall4 ensures precise patterning of embryonic limb and heart and provides a unifying mechanism for heart/hand syndromes.
Social participation prevents social isolation and loneliness among older adults while having numerous positive effects on their health and well-being in rapidly aging societies. We aimed to estimate ...the effect of retaining more natural teeth on social participation among older adults in Japan. The analysis used longitudinal data from 24,872 participants in the Japan Gerontological Evaluation Study (2010, 2013, and 2016). We employed a longitudinal modified treatment policy approach to determine the effect of several hypothetical scenarios (preventive scenarios and tooth loss scenarios) on frequent social participation (1 = at least once a week/0 = less than once a week) after a 6-y follow-up. The corresponding statistical parameters were estimated using targeted minimum loss-based estimation (TMLE) method. Number of teeth category (edentate/1–9/10–19/≥20) was treated as a time-varying exposure, and the outcome estimates were adjusted for time-varying (income, self-rated health, marital status, instrumental activities of daily living, vision loss, hearing loss, major comorbidities, and number of household members) and time-invariant covariates (age, sex, education, baseline social participation). Less frequent social participation was associated with older age, male sex, lower income, low educational attainment, and poor self-rated health at the baseline. Social participation improved when tooth loss prevention scenarios were emulated. The best preventive scenario (i.e., maintaining ≥20 teeth among each participant) improved social participation by 8% (risk ratio RR = 1.08; 95% confidence interval CI, 1.05–1.11). Emulated tooth loss scenarios gradually decreased social participation. A hypothetical scenario in which all the participants were edentate throughout the follow-up period resulted in a 11% (RR = 0.89; 95% CI, 0.84–0.94) reduction in social participation. Subsequent tooth loss scenarios showed 8% (RR = 0.92; 95% CI, 0.88–0.95), 6% (RR = 0.94; 95% CI, 0.91–0.97), and 4% (RR = 0.96; 95% CI, 0.93–0.98) reductions, respectively. Thus, among Japanese older adults, retaining a higher number of teeth positively affects their social participation, whereas being edentate or having a relatively lower number of teeth negatively affects their social participation.
The heart is one of the vital organs and is functionalized for blood circulation from its early development. Some vertebrates have altered their living environment from aquatic to terrestrial life ...over the course of evolution and obtained circulatory systems well adapted to their lifestyles. The morphology of the heart has been changed together with the acquisition of a sophisticated respiratory organ, the lung. Adaptation to a terrestrial environment requires the coordination of heart and lung development due to the intake of oxygen from the air and the production of the large amount of energy needed for terrestrial life. Therefore, vertebrates developed pulmonary circulation and a septated heart (four‐chambered heart) with venous and arterial blood completely separated. In this review, we summarize how vertebrates change the structures and functions of their circulatory systems according to environmental changes.
This figure shows the bulbus arteriosus (BA) formation mechanism by elnb in teleost cardiac development. BA is a unique cardiac organ in teleosts. The teleosts are thought to be well adapt to the aquatic environment through obtaining the BA (Modified from Moriyama et al., ).
Tbx5 and the Retinotectum Projection Koshiba-Takeuchi, Kazuko; Takeuchi, Jun K.; Matsumoto, Ken ...
Science (American Association for the Advancement of Science),
01/2000, Letnik:
287, Številka:
5450
Journal Article
Recenzirano
Dorsal and ventral aspects of the eye are distinct from the early stages of development. The developing eye cup grows dorsally, and the choroidal fissure is formed on its ventral side. Retinal axons ...from the dorsal and ventral retina project to the ventral and dorsal tectum, respectively. Misexpression of the Tbx5 gene induced dorsalization of the ventral side of the eye and altered projections of retinal ganglion cell axons. Thus, Tbx5 is involved in eye morphogenesis and is a topographic determinant of the visual projections between retina and tectum.
Epigenetic factors and cardiac development van Weerd, Jan Hendrick; Koshiba-Takeuchi, Kazuko; Kwon, Chulan ...
Cardiovascular research,
07/2011, Letnik:
91, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Congenital heart malformations remain the leading cause of death related to birth defects. Recent advances in developmental and regenerative cardiology have shed light on a mechanistic understanding ...of heart development that is controlled by a transcriptional network of genetic and epigenetic factors. This article reviews the roles of chromatin remodelling factors important for cardiac development with the current knowledge of cardiac morphogenesis, regeneration, and direct cardiac differentiation. In the last 5 years, critical roles of epigenetic factors have been revealed in the cardiac research field.
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