Heart regeneration offers a novel therapeutic strategy for heart failure. Unlike mammals, lower vertebrates such as zebrafish mount a strong regenerative response following cardiac injury. Heart ...regeneration in zebrafish occurs by cardiomyocyte proliferation and reactivation of a cardiac developmental program, as evidenced by induction ofgata4regulatory sequences in regenerating cardiomyocytes. Although many of the cellular determinants of heart regeneration have been elucidated, how injury triggers a regenerative program through dedifferentiation and epicardial activation is a critical outstanding question. Here, we show that NF-κB signaling is induced in cardiomyocytes following injury. Myocardial inhibition of NF-κB activity blocks heart regeneration with pleiotropic effects, decreasing both cardiomyocyte proliferation and epicardial responses. Activation ofgata4regulatory sequences is also prevented by NF-κB signaling antagonism, suggesting an underlying defect in cardiomyocyte dedifferentiation. Our results implicate NF-κB signaling as a key node between cardiac injury and tissue regeneration.
Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying ...repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine-freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine-freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.
In the embryo, the neural crest is an important population of cells that gives rise to diverse derivatives, including the peripheral nervous system and the craniofacial skeleton. Evolutionarily, the ...neural crest is of interest as an important innovation in vertebrates. Experimentally, it represents an excellent system for studying fundamental developmental processes, such as tissue induction. Classical embryologists have identified interactions between tissues that lead to neural crest formation. More recently, geneticists and molecular biologists have identified the genes that are involved in these interactions; this recent work has revealed that induction of the neural crest is a complex multistep process that involves many genes.
The distribution of effect sizes of genes underlying adaptation is unknown (Orr 2005). Are suites of traits that diverged under natural selection controlled by a few pleiotropic genes of large effect ...(major genes model), by many independently acting genes of small effect (infinitesimal model), or by a combination, with frequency inversely related to effect size (geometric model)? To address this we carried out a quantitative trait loci (QTL) study of a suite of 54 position traits describing body shapes of two threespine stickleback species: an ancestral Pacific marine form and a highly derived benthic species inhabiting a geologically young lake. About half of the 26 detected QTL affected just one coordinate and had small net effects, but several genomic regions affected multiple aspects of shape and had large net effects. The distribution of effect sizes followed the gamma distribution, as predicted by the geometric model of adaptation when detection limits are taken into account. The sex-determining chromosome region had the largest effect of any QTL. Ancestral sexual dimorphism was similar to the direction of divergence, and was largely eliminated during freshwater adaptation, suggesting that sex differences may provide variation upon which selection can act. Several shape QTL are linked to Eda, a major gene responsible for reduction of lateral body armor in freshwater. Our results are consistent with predictions of the geometric model of adaptation. Shape evolution in stickleback results from a few genes with large and possibly widespread effects and multiple genes of smaller effect.
Background Adults with a Fontan circulation tend to have myopenia and elevated adiposity when measured by dual energy x-ray absorptiometry. Bioelectrical impedance analysis is an alternative ...validated approach to assess body composition. We used bioelectrical impedance analysis to compare body composition between pediatric patients with a Fontan circulation and control individuals without heart disease. Methods and Results A retrospective chart review identified all patients aged <22 years with a Fontan circulation who presented for cardiopulmonary exercise testing and bioelectrical impedance analysis from April 2019 to January 2020. Data were compared with control subjects tested during the same period. We studied 47 patients with a Fontan circulation (53% boys; 15±3.1 years) and 165 controls (48% boys; 14.4±2.5 years). Fontan status was associated with shorter height, but similar age, sex, and overall body mass. Patients with Fontan had lower lean body mass (-12.0±22%, Z-score -0.5±1,
=0.005), skeletal muscle mass (-13.6±1.4%; Z-score, -0.5±1;
=0.004), skeletal muscle indexed to height (-10.3±13.3%; Z-score, -0.5±1;
=0.005), and higher percent body fat (+13.8±18.6%; Z-score, 0.4±1.2;
=0.03). Greater skeletal muscle mass was associated with higher peak oxygen consumption (
=0.52,
<0.0001) and oxygen pulse (
=0.68,
<0.0001). Patients who had suffered a late complication (ie, heart transplant referral or evidence of extracardiac organ dysfunction) of the Fontan operation (13 of 47, 27.7%) had lower skeletal muscle mass (
=0.048) and higher body fat percentage (
=0.003). Conclusions The Fontan circulation is associated with marked myopenia and increased adiposity. Higher muscle mass was associated with better exercise capacity. Fontan complications are associated with lower muscle mass and increased adiposity.
The Polaris-LAMP multi-modal 3-D gamma-ray imager is a radiation mapping and imaging platform which uses a commercial off-the-shelf (COTS) detector integrated with a contextual sensor localization ...and mapping platform. The integration of these systems enables a free-moving radiation imaging capability with proximity mapping, coded-aperture, and Compton imaging modalities, which can create 3-D reconstruction of photon sources from tens of keV to several MeV. Gamma-ray events are recorded using a segmented cadmium zinc telluride (CZT) detector (Polaris-H Quad by H3D Inc., Ann Arbor, MI, USA), while scene data are derived from a contextual sensor and computation package developed by Lawrence Berkeley National Laboratory which includes GPS, laser ranging, and inertial measurement sensors. An onboard computer uses these inputs to create rapidly updating pose (10 Hz) and 3-D scene estimates using a simultaneous localization and mapping (SLAM) algorithm. The precise gamma-ray event location and timing resolution of the Polaris CZT sensor enables Compton imaging above several hundred keV, while photon sources at lower images are localized using coded-aperture imaging techniques. The multi-modal imaging concept enables imaging of diverse radiation sources spanning from the 59-keV emission of 241 Am to the 1.1 and 1.3 MeV lines of 60 Co. This work focuses on the description of the operational principles of the detector system and demonstrating the 3-D imaging performance in a variety of source detection and mapping scenarios. As a proof of concept, we demonstrate mapping complex environments, including both point source and distributed-source environments using proximity, coded-aperture, and Compton imaging modalities. Furthermore, we show the successful use of the system to perform measurements in high-background environments through analysis of arrays of uranium hexafluoride cylinders at the Paducah UF6 project site.
Introduction Patients with congenital heart disease (CHD) often have pulmonary abnormalities and exercise intolerance following cardiac surgery. Cardiac rehabilitation (CR) improves exercise capacity ...in patients with CHD, but minimal study has been performed to see if resting and dynamic pulmonary performance improves following CR in those with prior cardiac surgery. Methods This was a retrospective cohort study of all patients who completed ≥12 weeks of CR from 2018 through 2022. Demographic, cardiopulmonary exercise test (CPET), spirometry, 6-minute walk, functional strength measures, and outcomes data were collected. Data are presented as medianIQR. A Student's t -test was used for comparisons between groups and serial measurements were measured with a paired t -test. A p < 0.05 was considered significant. Results There were a total of 37 patients age 16.7 (14.2–20.1) years; 46% male included. Patients with prior surgery ( n = 26) were more likely to have abnormal spirometry data than those without heart disease ( n = 11) (forced vital capacity FVC 76.7 69.1–84.3% vs. 96.4 88.1–104.7%, p = 0.002), but neither group experienced a significant change in spirometry. On CPET, peak oxygen consumption increased but there was no change in other pulmonary measures during exercise. Percent predicted FVC correlated with hand grip strength ( r = 0.57, p = 0.0003) and percent predicted oxygen consumption ( r = 0.43, p = 0.009). The number of prior sternotomies showed negative associations with both percent predicted FVC ( r = −0.43, p = 0.04) and FEV 1 ( r = −0.47, p = 0.02). Discussion Youth and young adults with a prior history of cardiac surgery have resting and dynamic pulmonary abnormalities that do not improve following CR. Multiple sternotomies are associated with worse pulmonary function.
Little is known about how sport and school restrictions early during the novel coronavirus 2019 (COVID-19) pandemic impacted exercise performance and body composition in youth with heart disease ...(HD).
A retrospective chart review was performed on all patients with HD who had serial exercise testing and body composition
bioimpedance analysis performed within 12 months before and during the COVID-19 pandemic. Formal activity restriction was noted as present or absent. Analysis was performed with a paired
-test.
There were 33 patients (mean age 15.3 ± 3.4 years; 46% male) with serial testing completed (18 electrophysiologic diagnosis, 15 congenital HD). There was an increase in skeletal muscle mass (SMM) (24.1 ± 9.2-25.9 ± 9.1 kg,
< 0.0001), weight (58.7 ± 21.5-63.9 ± 22 kg,
< 0.0001), and body fat percentage (22.7 ± 9.4-24.7 ± 10.4%,
= 0.04). The results were similar when stratified by age <18 years old (
= 27) or by sex (male 16, female 17), consistent with typical pubertal changes in this predominantly adolescent population. Absolute peak VO
increased, but this was due to somatic growth and aging as evidenced by no change in % of predicted peak VO
. There remained no difference in predicted peak VO
when excluding patients with pre-existing activity restrictions (
= 12). Review of similar serial testing in 65 patients in the 3 years before the pandemic demonstrated equivalent findings.
The COVID-19 pandemic and related lifestyle changes do not appear to have had substantial negative impacts on aerobic fitness or body composition in children and young adults with HD.
Heart rate variability is primarily regulated by the autonomic nervous system. Heart transplant recipients undergo surgical denervation of the graft, which results in interruption of autonomic ...innervation with resultant diminished heart rate variability although some degree of autonomic control may return. This study aimed to characterize heart rate variability in this population. We report a retrospective review of Holter monitor data from transplanted patients between 2005 and 2013. Studies with significant atrial or ventricular arrhythmias were excluded. We evaluated changes over time and compared standard time domain measures to published pediatric normal values. Data were reviewed from 582 monitors in 152 patients. We found that pediatric heart transplant recipients have lower heart rate variability than age‐matched controls and higher average heart rate in recipients older than 3 years. There is an increase in measures of variability through the first 3 years post‐transplant with plateau after that time. Surgical technique in regard to interruption of the vagus nerve does not affect variability, nor does underlying congenital vs acquired heart disease.
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