The positive effects of early powered mobility on children's psychosocial and play skills.

Powered mobility can have an important cognitive and psychosocial impact on young children who are unable to move independently. Twenty-three children with physical disabilities between the ages of 18 months and 6 years participated in this study. Data evaluating social skills, frequency of mobility play activities, frequency of interaction with toys/objects, and play/verbal developmental levels were collected at wheelchair evaluation, wheelchair delivery, and approximately 6 months later.

The impact of early powered mobility on parental stress, negative emotions, and family social interactions.

Powered mobility has been found to have positive effects on young children with severe physical disabilities, but the impact on the family has been less well documented. We evaluated the impact of early powered mobility on parental stress, negative emotions, perceived social interactions, and parental satisfaction with wheelchair characteristics such as size and durability. The participants were parents of 23 children with disabilities-10 with orthopedic disabilities (average age 30.

Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait.

An empirical test for branch-specific positive selection.

The use of phylogenetic analysis to predict positive selection specific to human genes is complicated by the very close evolutionary relationship with our nearest extant primate relatives, chimpanzees. To assess the power and limitations inherent in use of maximum-likelihood (ML) analysis of codon substitution patterns in such recently diverged species, a series of simulations was performed to assess the impact of several parameters of the evolutionary model on prediction of human-specific positive selection, including branch length and d(N)/d(S) ratio. Parameters were varied across a range of values observed in alignments of 175 transcription factor (TF) genes that were sequenced in 12 primate species.

Centrifugal migration of mesenchymal cells in embryonic lung.

Murine lung development begins at embryonic day (E) 9.5. Normal lung structure and function depend on the patterns of localization of differentiated cells.

Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling.

Background: The role of ss-catenin signaling in mesodermal lineage formation and differentiation has been elusive.

Methodology: To define the role of ss-catenin signaling in these processes, we used a Dermo1(Twist2)(Cre/+) line to target a floxed beta-catenin allele, throughout the embryonic mesenchyme. Strikingly, the Dermo1(Cre/+); beta-catenin(f/-) conditional Knock Out embryos largely phenocopy Pitx1(-/-)/Pitx2(-/-) double knockout embryos, suggesting that ss-catenin signaling in the mesenchyme depends mostly on the PITX family of transcription factors.

Human PAML browser: a database of positive selection on human genes using phylogenetic methods.

With the recent increase in the number of mammalian genomes being sequenced, large-scale genome scans for human-specific positive selection are now possible. Selection can be inferred through phylogenetic analysis by comparing the rates of silent and replacement substitution between related species. Maximum-likelihood (ML) analysis of codon substitution models can be used to identify genes with an accelerated pattern of amino acid substitution on a particular lineage.

Differential role of FGF9 on epithelium and mesenchyme in mouse embryonic lung.

Mesothelial Fibroblast Growth Factor 9 (Fgf9) has been demonstrated by inactivation studies in mouse to be critical for the proliferation of the mesenchyme. We now show that Fgf9 is also expressed at significant levels in the distal epithelium from the mid-pseudoglandular stages. Using mesenchymal-free lung endoderm culture, we show that FGF9 triggers the proliferation of the distal epithelium leading to the formation of a cyst-like structure.

Pediatric powered wheelchairs: results of a national survey of providers.

A national survey of providers of pediatric powered wheelchairs was conducted to collect background data on these professionals and to develop a "model" of their current assessment and recommendation practices. Data collected in the survey included provider demographics, frequency of powered wheelchair provision to young children, common reasons for not recommending a powered wheelchair, reasons why a child who is recommended a powered wheelchair does not receive one, current pediatric powered wheelchair assessment and recommendation practices, and subjective data regarding the efficacy of these practices and the impact of powered wheelchairs on children. Respondents rated the frequency with which they performed various wheelchair assessment and recommendation practices, and these ratings were analyzed to determine activities that were performed frequently.

VEGF-A signaling through Flk-1 is a critical facilitator of early embryonic lung epithelial to endothelial crosstalk and branching morphogenesis.

Vascular endothelial growth factor-A (VEGF-A) signaling directs both vasculogenesis and angiogenesis. However, the role of VEGF-A ligand signaling in the regulation of epithelial-mesenchymal interactions during early mouse lung morphogenesis remains incompletely characterized. Fetal liver kinase-1 (Flk-1) is a VEGF cognate receptor (VEGF-R2) expressed in the embryonic lung mesenchyme.

A catalog of nonsynonymous polymorphism on mouse chromosome 16.

Numerous phenotypic traits differ among inbred mice, and the genetic diversity of inbred strains has been exploited in studies of quantitative trait loci (QTL). Sequencing the mouse genome has resulted in improved tools for the study of QTL, but a comprehensive catalog of sequence variants between strains would be of great value in identifying and testing potentially causative alleles. A/J DNA was included in the Celera shotgun sequence of the mouse genome and C57BL/6 DNA was sequenced by an international consortium.

A novel function for the protein tyrosine phosphatase Shp2 during lung branching morphogenesis.

Branching morphogenesis of many organs, including the embryonic lung, is a dynamic process in which growth factor mediated tyrosine kinase receptor activation is required, but must be tightly regulated to direct ramifications of the terminal branches. However, the specific regulators that modulate growth factor signaling downstream of the tyrosine kinase receptor remain to be determined. Herein, we demonstrate for the first time an important function for the intracellular protein tyrosine phosphatase Shp2 in directing embryonic lung epithelial morphogenesis.

Molecular mechanisms of early lung specification and branching morphogenesis.

The "hard wiring" encoded within the genome that determines the emergence of the laryngotracheal groove and subsequently early lung branching morphogenesis is mediated by finely regulated, interactive growth factor signaling mechanisms that determine the automaticity of branching, interbranch length, stereotypy of branching, left-right asymmetry, and finally gas diffusion surface area. The extracellular matrix is an important regulator as well as a target for growth factor signaling in lung branching morphogenesis and alveolarization. Coordination not only of epithelial but also endothelial branching morphogenesis determines bronchial branching and the eventual alveolar-capillary interface.

Relevance of the Pediatric Powered Wheelchair Screening Test for children with cerebral palsy.

In a previous study we developed a cognitive assessment battery called the Pediatric Powered Wheelchair Screening Test (PPWST) to help clinicians determine a young child's readiness to drive a powered wheelchair. The current multicenter study sought to determine: (1) whether the PPWST is appropriate for use in a population of children with cerebral palsy (CP) who use joysticks to drive their wheelchair; (2) whether two additional factors (symbolic representation and coping) would increase the predictive power of the PPWST for this group and for children with orthopedic or neuromuscular disabilities only; and (3) whether the test was appropriate for children with severe motor impairments who use switches to control their wheelchair. Fifty children (27 males, 23 females) between the ages of 21 months and 6 years 11 months participated.

Growth factor signaling in lung morphogenetic centers: automaticity, stereotypy and symmetry.

Lung morphogenesis is stereotypic, both for lobation and for the first several generations of airways, implying mechanistic control by a well conserved, genetically hardwired developmental program. This program is not only directed by transcriptional factors and peptide growth factor signaling, but also co-opts and is modulated by physical forces. Peptide growth factors signal within repeating epithelial-mesenchymal temporospatial patterns that constitute morphogenetic centers, automatically directing millions of repetitive events during both stereotypic branching and nonstereotypic branching as well as alveolar surface expansion phases of lung development.

mSprouty2 inhibits FGF10-activated MAP kinase by differentially binding to upstream target proteins.

Murine Sprouty2 (mSpry2) is a conserved ortholog of Drosophila Sprouty, a gene that inhibits several tyrosine kinase receptor pathways, resulting in net reduction of mitogen-activated protein (MAP) kinase activation. However, the precise mechanism mediating mSpry2 function as a negative regulator in tyrosine kinase growth factor pathways that regulate diverse biological functions remains incompletely characterized. Fibroblast growth factor 10 (FGF10) is a key positive regulator of lung branching morphogenesis and induces epithelial expression of mSpry2 adjacent to mesenchymal sites of FGF10.

Do lung remodeling, repair, and regeneration recapitulate respiratory ontogeny?

Herein we posit that modeling of the lungs during morphogenesis, repair, and regeneration is tightly coordinated by conserved stimulatory and inhibitory signaling mechanisms, including specific transcriptional factors, cytokines, peptide growth factors, proteases, and matrix elements. This evolutionary-developmental (evo-devo) functional conservation has been extended to morphogenesis of the respiratory tracheae in Drosophila. Fifty or more genes direct fruit fly tracheal organogenesis.

Novel mechanisms in murine nitrofen-induced pulmonary hypoplasia: FGF-10 rescue in culture.

We evaluated the role of the key pulmonary morphogenetic gene fibroblast growth factor-10 (Fgf10) in murine nitrofen-induced primary lung hypoplasia, which is evident before the time of diaphragm closure. In situ hybridization and competitive RT-PCR revealed a profound disturbance in the temporospatial pattern as well as a 10-fold decrease in mRNA expression level of Fgf10 but not of the inducible inhibitor murine Sprouty2 (mSpry2) after nitrofen treatment. Exogenous FGF-10 increased branching not only of control lungs [13% (right) and 27% (left); P < 0.

Evidence that SPROUTY2 functions as an inhibitor of mouse embryonic lung growth and morphogenesis.

Experimental evidence is rapidly emerging that the coupling of positive regulatory signals with the induction of negative feedback modulators is a mechanism of fine regulation in development. Studies in Drosophila and chick have shown that members of the SPROUTY family are inducible negative regulators of growth factors that act through tyrosine kinase receptors. We and others have shown that Fibroblast Growth Factor 10 (FGF10) is a key positive regulator of lung branching morphogenesis.

The molecular basis of lung morphogenesis.

To form a diffusible interface large enough to conduct respiratory gas exchange with the circulation, the lung endoderm undergoes extensive branching morphogenesis and alveolization, coupled with angiogenesis and vasculogenesis. It is becoming clear that many of the key factors determining the process of branching morphogenesis, particularly of the respiratory organs, are highly conserved through evolution. Synthesis of information from null mutations in Drosophila and mouse indicates that members of the sonic hedgehog/patched/smoothened/Gli/FGF/FGFR/sprouty pathway are functionally conserved and extremely important in determining respiratory organogenesis through mesenchymal-epithelial inductive signaling, which induces epithelial proliferation, chemotaxis and organ-specific gene expression.

Cognitive predictors of young children's readiness for powered mobility.

Independent mobility in early childhood has been associated with the development of various cognitive and psychosocial skills. However, children with physical disabilities are not always able to move independently and may be at risk for delays in these areas. Early provision of powered mobility can offer young children an opportunity for independent mobility.