Overweight and cystic fibrosis: An unexpected challenge.

Achieving a healthy weight balance has been a central focus of care for people who have cystic fibrosis (CF). Over the years, the emphasis has primarily been on promoting weight gain to optimize pulmonary outcomes. With continued improvements in CF care, including highly effective CF modulators available for many people, the CF community is now experiencing a new challenge: addressing the concern that some people are gaining weight excessively. While at this time, we do not know to what extent overweight and obesity will affect health outcomes for people with CF, it is likely that excessive weight gain may have negative health impacts similar to those seen in the general population. In this paper, we review the history of nutritional guidelines for people with CF, as well as more recent trends toward overweight and obesity for some. A multidisciplinary approach is needed to collaboratively start the oftentimes difficult conversation regarding excessive weight gain, and to identify resources to help people achieve and maintain a healthy weight through diet, exercise, and behavioral modification.

The transcriptome of fracture healing defines mechanisms of coordination of skeletal and vascular development during endochondral bone formation.

Fractures initiate one round of endochondral bone formation in which callus cells differentiate in a synchronous manner that temporally phenocopies the spatial variation of endochondral development of a growth plate. During fracture healing C57BL/6J (B6) mice initiate chondrogenesis earlier and develop more cartilage than bone, whereas C3H/HeJ (C3H) mice initiate osteogenesis earlier and develop more bone than cartilage. Comparison of the transcriptomes of fracture healing in these strains of mice identified the genes that showed differences in timing and quantitative expression and encode for the variations in endochondral bone development of the two mouse strains. The complement of strain-dependent differences in gene expression was specifically associated with ontologies related to both skeletal and vascular formation. Moreover, the differences in gene expression associated with vascular tissue formation during fracture healing were correlated with the underlying differences in development and function of the cardiovascular systems of these two strains of mice. Significant differences in gene expression associated with bone morphogenetic protein/transforming growth factor ß (BMP/TGF-ß) signal-transduction pathways were identified between the two strains, and a network of differentially expressed genes specific to the MAP kinase cascade was further defined as a subset of the genes of the BMP/TGF-ß pathways. Other signal-transduction pathways that showed significant strain-specific differences in gene expression included the RXR/PPAR and G protein-related pathways. These data identify how bone and vascular regeneration are coordinated through expression of common sets of transcription and morphogenetic factors and suggest that there is heritable linkage between vascular and skeletal tissue development during postnatal regeneration.

Diverse dependencies of developing Merkel innervation on the trkA and both full-length and truncated isoforms of trkC.

This study demonstrates that innervation dependent on two different neurotrophin tyrosine kinase (trk) receptors can form the same types of sensory endings (Merkel endings) in the same target (Merkel cells of vibrissa follicles). Some endings transiently express trkA during their initial development, whereas others express trkC throughout their development. Consequently, elimination of kinase domains of either trkA or trkC each result in a partial loss of Merkel endings, whereas absence of kinase domains of both receptors results in a total loss. At the onset of Merkel ending development, at least one kinase-lacking trkC isoform is transiently expressed on all the follicle cells, while neurotrophin 3 is transiently expressed only in the cells at the middle third of the follicle where the Merkel endings and cells develop. This transient non-neuronal expression of truncated trkC is essential for development of any Merkel endings, whereas some Merkel endings and cells still begin to develop in the absence of neurotrophin 3. Therefore, truncated trkC plays a more important role in the development of this innervation than kinase forms of trkA or trkC or of NT3, the only known ligand for trkC receptors.