Monroe Carell Jr. Children's Hospital at Vanderbilt

About: Monroe Carell Jr. Children's Hospital at Vanderbilt is a based out in . It is known for research contribution in the topics: Population & Medicine. The organization has 1046 authors who have published 1262 publications receiving 28063 citations. The organization is also known as: Vanderbilt Children's Hospital.

Tgfβ signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development

Abstract: The transforming growth factorbeta (Tgfbeta) signaling pathway plays crucial roles in many biological processes. To understand the role(s) of Tgfbeta signaling during cardiogenesis in vivo and to overcome the early lethality of Tgfbr2(-/-) embryos, we applied a Cre/loxp system to specifically inactivate Tgfbr2 in either the myocardium or the endothelium of mouse embryos. Our results show that Tgfbr2 in the myocardium is dispensable for cardiogenesis in most embryos. Contrary to the prediction from results of previous in vitro collagen gel assays, inactivation of Tgfbr2 in the endocardium does not prevent atrioventricular cushion mesenchyme formation, arguing against its essential role in epithelium-mesenchyme transformation in vivo. We further demonstrate that Tgfbeta signaling is required for the proper remodeling of the atrioventricular canal and for cardiac looping, and that perturbation in Tgfbeta signaling causes the double-inlet left ventricle (DILV) defect. Thus, our study provides a unique mouse genetic model for DILV, further characterization of which suggests a potential cellular mechanism for the defect.

Human Milk Oligosaccharides Exhibit Antimicrobial and Antibiofilm Properties against Group B Streptococcus.

Abstract: Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that causes invasive infections in both children and adults During pregnancy, GBS is a significant cause of infection of the fetal membranes (chorioamnionitis), which can lead to intra-amniotic infection, preterm birth, stillbirth, and neonatal sepsis Recently, breastfeeding has been thought to represent a potential mode of GBS transmission from mother to newborn, which might increase the risk for late-onset sepsis Little is known, however, about the molecular components of breast milk that may support or prevent GBS colonization In this study, we examine how human milk oligosaccharides (HMOs) affect the pathogenesis of GBS HMOs from discrete donor samples were isolated and profiled by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) Growth and biofilm assays show that HMOs from mothers of specific milk groups can modulate the growth and biofilm formation of GBS High-resolution fiel

General mitochondrial trifunctional protein (TFP) deficiency as a result of either α- or β-subunit mutations exhibits similar phenotypes because mutations in either subunit alter TFP complex expression and subunit turnover

Abstract: The mitochondrial trifunctional protein (TFP) is a multienzyme complex of the β-oxidation cycle. Human TFP is an octamer composed of four α-subunits harboring long-chain enoyl-CoA hydratase and long-chain L-3-hydroxyacyl-CoA dehydrogenase and four β-subunits encoding long-chain 3-ketoacyl-CoA thiolase. Mutations in either subunit may result in general TFP deficiency with reduced activity of all three enzymes. We report five new patients with α-subunit mutations and compare general TFP deficiency caused by α-subunit mutations (n = 15) to that caused by β-subunit mutations (n = 13) with regard to clinical features, enzyme activity, mutations, thiolase expression, and thiolase protein turnover. Among patients with α-subunit mutations, the same three heterogeneous phenotypes reported in patients with β-subunit mutations were observed: a lethal form with predominating cardiomyopathy; an infancy-onset, hepatic presentation; and a milder, later-onset, neuromyopathic form. Maternal HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) occurred with an incidence of 15 to 20%, as in families with β-subunit mutations. Enzyme assays in fibroblasts revealed an identical biochemical pattern in both groups. α-Subunit mutational analysis demonstrated molecular heterogeneity, with 53% (9 of 17) truncating mutations. In contrast, patients with β-subunit mutations had predominantly missense mutations. Thiolase expression in fibroblasts was as markedly reduced in α-subunit patients as in the β-subunit group with similarly increased thiolase degradation, presumably secondary to TFP complex instability. TFP deficiency as a result of either α- or β-subunit mutations presents with similar, heterogeneous phenotypes. Both α- and β-subunit mutations result in TFP complex instability, demonstrating that the mechanism of disease is the same in α- or β-mutation-derived disease and explaining the biochemical and clinical similarities.

Frequency and Correlates of Service Access Among Youth with Autism Transitioning to Adulthood

Abstract: This study examined service receipt and unmet service needs among youth with autism spectrum disorders (ASD) in their last year of high school, as well as the youth (intellectual disability, race/ethnicity, autism severity, comorbid psychiatric diagnoses, behavior problems, adaptive behavior) and family (income, parental health, parental depressive symptoms, parental anxiety) correlates of service access. Thirty-nine families of youth with ASD participated. Data were collected via parental interview/questionnaire and youth psychological evaluation. Results suggested that this sample was underserved relative to a nationally-representative cohort. Those with a comorbid psychiatric diagnosis and lower levels of adaptive behavior received more services. Greater unmet needs were reported for youth who were racial/ethnic minorities, who had more behavior problems, and whose parents had greater anxiety.