BackgroundRecent increases in genomic studies of the developing human fetus and neonate have led to a need for widespread characterization of the functional roles of genes at different developmental stages. The Gene Ontology (GO), a valuable and widely-used resource for characterizing gene function, offers perhaps the most suitable functional annotation system for this purpose. However, due in part to the difficulty of studying molecular genetic effects in humans, even the current collection of comprehensive GO annotations for human genes and gene products often lacks adequate developmental context for scientists wishing to study gene function in the human fetus.DescriptionThe Developmental FunctionaL Annotation at Tufts (DFLAT) project aims to improve the quality of analyses of fetal gene expression and regulation by curating human fetal gene functions using both manual and semi-automated GO procedures. Eligible annotations are then contributed to the GO database and included in GO releases of human data. DFLAT has produced a considerable body of functional annotation that we demonstrate provides valuable information about developmental genomics. A collection of gene sets (genes implicated in the same function or biological process), made by combining existing GO annotations with the 13,344 new DFLAT annotations, is available for use in novel analyses. Gene set analyses of expression in several data sets, including amniotic fluid RNA from fetuses with trisomies 21 and 18, umbilical cord blood, and blood from newborns with bronchopulmonary dysplasia, were conducted both with and without the DFLAT annotation.ConclusionsFunctional analysis of expression data using the DFLAT annotation increases the number of implicated gene sets, reflecting the DFLAT’s improved representation of current knowledge. Blinded literature review supports the validity of newly significant findings obtained with the DFLAT annotations. Newly implicated significant gene sets also suggest specific hypotheses for future research. Overall, the DFLAT project contributes new functional annotation and gene sets likely to enhance our ability to interpret genomic studies of human fetal and neonatal development.
BackgroundThe present study demonstrates that the ubiquitin E3 ligase, Pellino‐1 (Peli1), is an important angiogenic molecule under the control of vascular endothelial growth factor (VEGF) receptor 2/Flk‐1. We have previously reported increased survivability of ischemic skin flap tissue by adenovirus carrying Peli1 (Ad‐Peli1) gene therapy in Flk‐1+/− mice.Methods and ResultsTwo separate experimental groups of mice were subjected to myocardial infarction (MI) followed by the immediate intramyocardial injection of adenovirus carrying LacZ (Ad‐LacZ) (1×109 pfu) or Ad‐Peli1 (1×109 pfu). Heart tissues were collected for analyses. Compared with wild‐type (WTMI) mice, analysis revealed decreased expressions of Peli1, phosphorylated (p‐)Flk‐1, p‐Akt, p‐eNOS, p‐MK2, p‐IκBα, and NF‐κB and decreased vessel densities in Flk‐1+/− mice subjected to MI (Flk‐1+/− MI). Mice (CD1) treated with Ad‐Peli1 after the induction of MI showed increased β‐catenin translocation to the nucleus, connexin 43 expression, and phosphorylation of Akt, eNOS, MK2, and IκBα, that was followed by increased vessel densities compared with the Ad‐LacZ–treated group. Echocardiography conducted 30 days after surgery showed decreased function in the Flk1+/− MI group compared with WTMI, which was restored by Ad‐Peli1 gene therapy. In addition, therapy with Ad‐Peli1 stimulated angiogenic and arteriogenic responses in both CD1 and Flk‐1+/− mice following MI. Ad‐Peli1 treatment attenuated cardiac fibrosis in Flk‐1+/− MI mice. Similar positive results were observed in CD1 mice subjected to MI after Ad‐Peli1 therapy.ConclusionOur results show for the first time that Peli1 plays a unique role in salvaging impaired collateral blood vessel formation, diminishes fibrosis, and improves myocardial function, thereby offering clinical potential for therapies in humans to mend a damaged heart following MI.
Background: Cellulite is a common aesthetic condition that affects the majority of women. It is characterized by the inhomogeneous appearance of the skin overlying the gluteal and the posterior thigh region. Despite a wide array of treatment options, little has been done to evaluate the anatomical basis of cellulite formation. This study used ultrasound to visualize subcutaneous changes of cellulite to aid with treatment guidance and complication avoidance. Methods: Cellulite dimples were examined on the bilateral thigh and buttock regions of 50 consecutive women and each dimple was scored with the Hexsel Cellulite Scoring System based on severity. Cellulite dimples were then analyzed by ultrasound to identify the presence, orientation, and origination of subcutaneous fibrous bands and the presence of associated vascular structures. Results: Two hundred total sites were examined, with 173 dimples identified. Of these, 169 demonstrated the presence of fibrous bands (97.6 percent). The majority of bands demonstrated an oblique (versus perpendicular) orientation to the skin (84.4 percent), with the majority (90.2 percent) taking origin from the superficial fascia (versus the deep fascia). Overall, 11 percent of bands had an associated vascular structure. When stratified by body mass index, overweight and obese patients had a higher likelihood of having an associated blood vessel visualized (p = 0.01). Results were similar for dimples in the thigh compared to those located in the buttock region. Conclusions: Ultrasound appears to be a valid technique to image the subcutaneous architecture of cellulite. This technology can help guide surgeons in real time to improve outcomes and minimize complications while performing cellulite treatments.
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