, a bio/informatics shared resource is still "open for business" - Visit the CDS website
The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
To identify valid measures of vocal development in young children with autism spectrum disorder in the early stages of language learning, we evaluated the convergent validity, divergent validity, and sensitivity to change (across 12 months) of two measures of vocal communication and two measures of vocal complexity through conventional coding of communication samples. Participants included 87 children with autism spectrum disorder (M = 23.42 months at entry). All four vocal variables demonstrated consistent evidence of convergent validity, divergent validity, and sensitivity to change with large effect sizes for convergent validity and sensitivity to change. The results highlight the value of measuring vocal communication and vocal complexity in future studies.
The mechanisms regulating endothelial cell response to hemodynamic forces required for heart valve development, especially valve remodeling, remain elusive. Tie1, an endothelial specific receptor tyrosine kinase, is up-regulated by oscillating shear stress and is required for lymphatic valve development. In this study, we demonstrate that valvular endothelial Tie1 is differentially expressed in a dynamic pattern predicted by disturbed flow during valve remodeling. Following valvular endocardial specific deletion of Tie1 in mice, we observed enlarged aortic valve leaflets, decreased valve stiffness and valvular insufficiency. Valve abnormalities were only detected in late gestation and early postnatal mutant animals and worsened with age. The mutant mice developed perturbed extracellular matrix (ECM) deposition and remodeling characterized by increased glycosaminoglycan and decreased collagen content, as well as increased valve interstitial cell expression of Sox9, a transcription factor essential for normal ECM maturation during heart valve development. This study provides the first evidence that Tie1 is involved in modulation of late valve remodeling and suggests that an important Tie1-Sox9 signaling axis exists through which disturbed flows are converted by endocardial cells to paracrine Sox9 signals to modulate normal matrix remodeling of the aortic valve.
Copyright © 2019. Published by Elsevier Inc.
p63 is a transcriptional regulator of ectodermal development that is required for basal cell proliferation and stem cell maintenance. p73 is a closely related p53 family member that is expressed in select p63-positive basal cells and can heterodimerize with p63. p73-/- mice lack multiciliated cells and have reduced numbers of basal epithelial cells in select tissues; however, the role of p73 in basal epithelial cells is unknown. Herein, we show that p73-deficient mice exhibit delayed wound healing despite morphologically normal-appearing skin. The delay in wound healing is accompanied by decreased proliferation and increased levels of biomarkers of the DNA damage response in basal keratinocytes at the epidermal wound edge. In wild-type mice, this same cell population exhibited increased p73 expression after wounding. Analyzing single-cell transcriptomic data, we found that p73 was expressed by epidermal and hair follicle stem cells, cell types required for wound healing. Moreover, we discovered that p73 isoforms expressed in the skin (ΔNp73) enhance p63-mediated expression of keratinocyte genes during cellular reprogramming from a mesenchymal to basal keratinocyte-like cell. We identified a set of 44 genes directly or indirectly regulated by ΔNp73 that are involved in skin development, cell junctions, cornification, proliferation, and wound healing. Our results establish a role for p73 in cutaneous wound healing through regulation of basal keratinocyte function.
Great progress has been made in cancer therapeutics. However, metastasis remains the predominant cause of death from cancer. Importantly, metastasis can manifest many years after initial treatment of the primary cancer. This is because cancer cells can remain dormant before forming symptomatic metastasis. An important question is whether metastasis research should focus on the early treatment of metastases, before they are clinically evident ("overt"), or on developing treatments to stop overt metastasis (stage IV cancer). In this commentary we want to clarify why it is important that all avenues of treatment for stage IV patients are developed. Indeed, future treatments are expected to go beyond the mere shrinkage of overt metastases and will include strategies that prevent disseminated tumor cells from emerging from dormancy.
The relation between caregiver follow-in utterances with verbs presented in different states of dyadic engagement and later child expressive verb vocabulary in children with autism spectrum disorder (ASD) was examined in 29 toddlers with ASD and their caregivers. Caregiver verb input in follow-in utterances presented during higher order supported joint engagement (HSJE) accounted for a significant, large amount of variance in later child verb vocabulary; R= .26. This relation remained significant when controlling for early verb vocabulary or verb input in lower support engagement states. Other types of talk in follow-in utterances in HSJE did not correlate with later verb vocabulary. These findings are an important step towards identifying interactional contexts that facilitate verb learning in children with ASD.
The goal of this protocol is to describe a method for the dissection of mouse embryos and visualization of embryonic mouse ventricular chambers during heart development using ventricular specific fluorescent reporter knock-in mice (MLC-2v-tdTomato mice). Heart development involves a linear heart tube formation, the heart tube looping, and four chamber septation. These complex processes are highly conserved in all vertebrates. The mouse embryonic heart has been widely used for heart developmental studies. However, due to their extremely small size, dissecting mouse embryonic hearts is technically challenging. In addition, visualization of cardiac chamber formation often needs in situ hybridization, beta-galactosidase staining using LacZ reporter mice, or immunostaining of sectioned embryonic hearts. Here, we describe how to dissect mouse embryonic hearts and directly visualize ventricular chamber formation of MLC-2v-tdTomato mice using whole mount epifluorescent microscopy. With this method, it is possible to directly examine heart tube formation and looping, and four chamber formation without further experimental manipulation of mouse embryos. Although the MLC-2v-tdTomato reporter knock-in mouse line is used in this protocol as an example, this protocol can be applied to other heart-specific fluorescent reporter transgenic mouse lines.
INTRODUCTION - Metabolic stress (e.g., gestational diabetes mellitus (GDM) and obesity) and infections are common during pregnancy, impacting fetal development and the health of offspring. Such antenatal stresses can differentially impact male and female offspring. We sought to determine how metabolic stress and maternal immune activation (MIA), either alone or in combination, alters inflammatory gene expression within the placenta and whether the effects exhibited sexual dimorphism.
METHODS - Female C57BL/6 J mice were fed a normal diet or a high fat diet for 6 weeks prior to mating, with the latter diet inducing a GDM phenotype during pregnancy. Dams within each diet group at gestational day (GD) 12.5 received either an intraperitoneal injection of the viral mimic, polyinosinic:polycytidylic acid (poly(I:C)) or saline. Three hours post injection; placentae were collected and analyzed for changes in the expression of 248 unique immune genes.
RESULTS - Placental immune gene expression was significantly altered by GDM, MIA and the combination of the two (GDM+MIA). mRNA expression was generally lower in placentae of mice exposed to GDM alone compared with the other experimental groups, while mice exposed to MIA exhibited the highest transcript levels. Notably, fetal/placental sex influenced the responses of many immune genes to both metabolic and inflammatory stress.
DISCUSSION - GDM and MIA provoke inflammatory responses within the placenta and such effects exhibit sexual dimorphism. The combination of these stressors impacts the placenta differently than either condition alone. These findings may help explain sexual dimorphism observed in adverse pregnancy outcomes in human offspring exposed to similar stressors.
Copyright © 2019. Published by Elsevier Ltd.
In a screen for human kinases that regulate Xenopus laevis embryogenesis, we identified Nagk and other components of the UDP-GlcNAc glycosylation salvage pathway as regulators of anteroposterior patterning and Wnt signaling. We find that the salvage pathway does not affect other major embryonic signaling pathways (Fgf, TGFβ, Notch, or Shh), thereby demonstrating specificity for Wnt signaling. We show that the role of the salvage pathway in Wnt signaling is evolutionarily conserved in zebrafish and Drosophila. Finally, we show that GlcNAc is essential for the growth of intestinal enteroids, which are highly dependent on Wnt signaling for growth and maintenance. We propose that the Wnt pathway is sensitive to alterations in the glycosylation state of a cell and acts as a nutritional sensor in order to couple growth/proliferation with its metabolic status. We also propose that the clinical manifestations observed in congenital disorders of glycosylation (CDG) in humans may be due, in part, to their effects on Wnt signaling during development.
Copyright © 2019 Elsevier B.V. All rights reserved.
The mechanism of how organ shape emerges and specifies cell fate is not understood. Pancreatic duct and endocrine lineages arise in a spatially distinct domain from the acinar lineage. Whether these lineages are pre-determined or settle once these niches have been established remains unknown. Here, we reconcile these two apparently opposing models, demonstrating that pancreatic progenitors re-localize to establish the niche that will determine their ultimate fate. We identify a p120ctn-regulated mechanism for coordination of organ architecture and cellular fate mediated by differential E-cadherin based cell sorting. Reduced p120ctn expression is necessary and sufficient to re-localize a subset of progenitors to the peripheral tip domain, where they acquire an acinar fate. The same mechanism is used re-iteratively during endocrine specification, where it balances the choice between the alpha and beta cell fates. In conclusion, organ patterning is regulated by p120ctn-mediated cellular positioning, which precedes and determines pancreatic progenitor fate.
Copyright © 2019 Elsevier Inc. All rights reserved.