Fibroblast Growth Factor 10 and Vertebrate Limb Development

Early limb development requires fibroblast growth factor (Fgf)-mediated coordination between growth and patterning to ensure the proper formation of a functional organ. The apical ectodermal ridge (AER) is a domain of thickened epithelium located at the distal edge of the limb bud that coordinates outgrowth along the proximodistal axis. Considerable amount of work has been done to elucidate the cellular and molecular mechanisms underlying induction, maintenance and regression of the AER. Fgf10, a paracrine Fgf that elicits its biological responses by activating the fibroblast growth factor receptor 2b (Fgfr2b), is crucial for governing proximal distal outgrowth as well as patterning and acts upstream of the known AER marker Fgf8. A transgenic mouse line allowing doxycycline-based inducible and ubiquitous expression of a soluble form of Fgfr2b has been extensively used to identify the role of Fgfr2b ligands at different time points during development. Overexpression of soluble Fgfr2b (sFgfr2b) post-AER induction leads to irreversible loss of cellular β-catenin organization and decreased Fgf8 expression in the AER. A similar approach has been carried out pre-AER induction. The observed limb phenotype is similar to the severe proximal truncations observed in human babies exposed to thalidomide, which has been proposed to block the Fgf10-AER-Fgf8 feedback loop. Novel insights on the role of Fgf10 signaling in limb formation pre- and post-AER induction are summarized in this review and will be integrated with possible future investigations on the role of Fgf10 throughout limb development

Fibroblast Growth Factor 10 in Pancreas Development and Pancreatic Cancer

The tenacious prevalence of human pancreatic diseases such as diabetes mellitus and adenocarcinoma has prompted huge research interest in better understanding of pancreatic organogenesis. The plethora of signaling pathways involved in pancreas development is activated in a highly coordinated manner to assure unmitigated development and morphogenesis in vertebrates. Therefore, a complex mesenchymal–epithelial signaling network has been implicated to play a pivotal role in organogenesis through its interactions with other germ layers, specifically the endoderm. The Fibroblast Growth Factor Receptor FGFR2-IIIb splicing isoform (FGFR2b) and its high affinity ligand Fibroblast Growth Factor 10 (FGF10) are expressed in the epithelium and mesenchyme, respectively, and therefore are well positioned to transmit mesenchymal to epithelial signaling. FGF10 is a typical paracrine FGF and chiefly mediates biological responses by activating FGFR2b with heparin/heparan sulfate (HS) as cofactor. A substantial number of studies using genetically engineered mouse models have demonstrated an essential role of FGF10 in the development of many organs and tissues including the pancreas. During mouse embryonic development, FGF10 signaling is crucial for epithelial cell proliferation, maintenance of progenitor cell fate and branching morphogenesis in the pancreas. FGF10 is also implicated in pancreatic cancer, and that overexpression of FGFR2b is associated with metastatic invasion. A thorough understanding of FGF10 signaling machinery and its crosstalk with other pathways in development and pathological states may provide novel opportunities for pancreatic cancer targeted therapy and regenerative medicine

FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling

Ischemia-reperfusion (I/R) is a common cause of acute kidney injury (AKI), which is associated with high mortality and poor outcomes. Autophagy plays important roles in the homeostasis of renal tubular cells (RTCs) and is implicated in the pathogenesis of AKI, although its role in the process is complex and controversial. Fibroblast growth factor 10 (FGF10), a multifunctional FGF family member, was reported to exert protective effect against cerebral ischemia injury and myocardial damage. Whether FGF10 has similar beneficial effect, and if so whether autophagy is associated with the potential protective activity against AKI has not been investigated. Herein, we report that FGF10 treatment improved renal function and histological integrity in a rat model of renal I/R injury. We observed that FGF10 efficiently reduced I/R-induced elevation in blood urea nitrogen, serum creatinine as well as apoptosis induction of RTCs. Interestingly, autophagy activation following I/R was suppressed by FGF10 treatment based on the immunohistochemistry staining and immunoblot analyses of LC3, Beclin-1 and SQSTM1/p62. Moreover, combined treatment of FGF10 with Rapamycin partially reversed the renoprotective effect of FGF10 suggesting the involvement of mTOR pathway in the process. Interestingly, FGF10 also inhibited the release of HMGB1 from the nucleus to the extracellular domain and regulated the expression of inflammatory cytokines such as TNF-α, IL-1β and IL-6. Together, these results indicate that FGF10 could alleviate kidney I/R injury by suppressing excessive autophagy and inhibiting inflammatory response and may therefore have the potential to be used for the prevention and perhaps treatment of I/R-associated AKI

An Improved Complexity Bound for Computing the Topology of a Real Algebraic Space Curve

We propose a new algorithm to compute the topology of a real algebraic space curve. The novelties of this algorithm are a new technique to achieve the lifting step which recovers points of the space curve in each plane fiber from several projections and a weaken notion of generic position. As opposed to previous work, our sweep generic position does not require that x-critical points have different x-coordinates. The complexity of achieving this sweep generic position is thus no longer a bottleneck in term of complexity. The bit complexity of our algorithm is O(d^18 + d ^17 t) where d and t bound the degree and the bitsize of the integer coefficients of the defining polynomials of the curve and polylogarithmic factors are ignored. To the best of our knowledge, this improves upon the best currently known results at least by a factor of d 2

Analysis for Soil Moisture in Jiangsu Province, China, Using GLDAS Data

In this chapter, we present the analysis for the evolution characteristics of temperature, precipitation, and soil moisture. We choose a newly developed method that is based on the information flow (IF) concept to research the causality between annual mean temperature, precipitation, and soil moisture in Jiangsu province, China, from 1961 to 2011 by using the Global Land Data Assimilation System (GLDAS). The correlation and the causality of air temperature and precipitation on soil moisture were compared and discussed. The causality value of 0–10 cm layer is significantly different from zero, while the deeper, in comparison to the surface layer, is negligible. This result unambiguously shows the causality in the sense that the precipitation increase and the temperature decrease are causing the shallow soil moisture to increase. Temperature and all layers of soil moisture have a negative correlation, but precipitation inverses. Precipitation strongly has the greatest effects on soil moisture in the surface layer, though the rest layers are not obvious

Amino-functionalized mesoporous silica based polyethersulfone-polyvinylpyrrolidone composite membranes for elevated temperature proton exchange membrane fuel cells

It is important to find alternative membranes to the state-of-the-art polybenzimidazole based high temperature proton exchange membranes with high proton conductivity at elevated temperature but with simple synthesis procedures. In this work, inorganic-organic nanostructured hybrid membranes are developed based on a polyethersulfone-polyvinylpyrrolidone (PES-PVP) polymeric matrix with hollow mesoporous silica (HMS), amino-functionalized hollow mesoporous silica (NH2-HMS) and amino-functionalized mesoporous silica (NH2-meso-silica). The composite membranes show a significant increase in proton conductivity and a decrease in the activation energy for proton diffusion in comparison with the phosphoric acid (H3PO4, PA) doped PES-PVP membrane. And the composite membrane with NH2-HMS shows the best performance under the conditions in this study, achieving the highest proton conductivity of 1.52 × 10-1 S cm-1 and highest peak power density of 480 mW cm-2 at 180 °C under anhydrous conditions, which is 92.7% higher than that of the PA doped PES-PVP membrane at identical conditions. Such enhancement results from the facilitated proton transportation in the ordered mesoporous channels via the hydrogen bond between the -NH2 groups and H3PO4. The high water retention capability of silica materials with a hollow structure also contributes to the decrease of the activation of proton diffusion. Consequently, the results show promising potential of the NH2-HMS based PES-PVP composite membrane for the elevated temperature proton exchange membrane fuel cells

A Comprehensive Analysis of Fibroblast Growth Factor Receptor 2b Signaling on Epithelial Tip Progenitor Cells During Early Mouse Lung Branching Morphogenesis

This study demonstrates that FGF10/FGFR2b signaling on distal epithelial progenitor cells, via ß-catenin/EP300, controls, through a comprehensive set of developmental genes, morphogenesis, and differentiation. Fibroblast growth factor (FGF) 10 signaling through FGF receptor 2b (FGFR2b) is mandatory during early lung development as the deletion of either the ligand or the receptor leads to lung agenesis. However, this drastic phenotype previously hampered characterization of the primary biological activities, immediate downstream targets and mechanisms of action. Through the use of a dominant negative transgenic mouse model (Rosa26rtTA; tet(o)sFgfr2b), we conditionally inhibited FGF10 signaling in vivo in E12.5 embryonic lungs via doxycycline IP injection to pregnant females, and in vitro by culturing control and experimental lungs with doxycycline. The impact on branching morphogenesis 9 h after doxycycline administration was analyzed by morphometry, fluorescence and electron microscopy. Gene arrays at 6 and 9 h following doxycycline administration were carried out. The relationship between FGF10 and ß-catenin signaling was also analyzed through in vitro experiments using IQ1, a pharmacological inhibitor of ß-catenin/EP300 transcriptional activity. Loss of FGF10 signaling did not impact proliferation or survival, but affected both adherens junctions (up-regulation of E-cadherin), and basement membrane organization (increased laminin). Gene arrays identified multiple direct targets of FGF10, including main transcription factors. Immunofluorescence showed a down-regulation of the distal epithelial marker SOX9 and mis-expression distally of the proximal marker SOX2. Staining for the transcriptionally-active form of ß-catenin showed a reduction in experimental vs. control lungs. In vitro experiments using IQ1 phenocopied the impacts of blocking FGF10. This study demonstrates that FGF10/FGFR2b signaling on distal epithelial progenitor cells via ß-catenin/EP300 controls, through a comprehensive set of developmental genes, cell adhesion, and differentiation

Are metal-free pristine carbon nanotubes electrocatalytically active?

Metal-free (i.e., residual metallic impurities-blocked) carbon nanotubes (CNTs) do show electrocatalytic activity for H2 evolution, O2 evolution and O2 reduction reactions (HER, OER & ORR) in alkaline solutions, but their activities strongly depend on the number of walls or inner tubes with a maximum for CNTs with 2–3 walls

Transcriptome profiling and digital gene expression by deep-sequencing in normal/regenerative tissues of planarian Dugesia japonica

AbstractPlanarians exhibit an extraordinary ability to regenerate lost body parts which is attributed to an abundance of pluripotent somatic stem cells called neoblasts. In this article, we report a transcriptome sequence of a Planaria subspecies Dugesia japonica derived by high-throughput sequencing. In addition, we researched transcriptome changes during different periods of regeneration by using a tag-based digital gene expression (DGE) system. Consequently, 11,913,548 transcriptome sequencing reads were obtained. Finally, these reads were eventually assembled into 37,218 unique unigenes. These assembled unigenes were annotated with various methods. Transcriptome changes during planarian regeneration were investigated by using a tag-based DGE system. We obtained a sequencing depth of more than 3.5million tags per sample and identified a large number of differentially expressed genes at various stages of regeneration. The results provide a fairly comprehensive molecular biology background to the research on planarian development, particularly with regard to its regeneration progress

The Effect of Histological Subtypes on Outcomes of Stage IV Epithelial Ovarian Cancer

Introduction: To examined survival outcome by histological subtypes in de novo stage IV epithelial ovarian cancer (EOC).Methods: Between 2004 and 2015, patients with stage IV EOC were included using the Surveillance, Epidemiology, and End Results program. The effects of histological subtypes on overall survival (OS) were assessed using Kaplan–Meier and multivariable Cox regression analyses.Results: We identified 5,953 patients including 5,351 (89.9%), 249 (4.2%), 145 (2.4%), and 208 (3.4%) patients with high-grade serous, endometrioid, mucinous, and clear cell subtypes, respectively. The 5-year OS rates were 28.1, 38.6, 14.2, and 18.8% in patients with high-grade serous, endometrioid, mucinous, and 18.8% clear cell subtypes, respectively, (p < 0.001). Multivariate analyses indicated that histological subtype was an independent predictor of OS. Using the high-grade serous subtype as a reference, OS was comparable for the endometrioid subtype (hazard ratio (HR) 0.915, 95% confidence interval) (CI 0.772–1.085, p = 0.305), but significantly lower for mucinous (HR 3.292, 95% CI 2.701–4.011, p < 0.001) and clear cell subtypes (HR 1.820, 95% CI 1.546–2.141, p < 0.001). Patients with no residual tumor had better OS in the high-grade serous and endometrioid subtypes compared to patients with residual tumors. However, the residual tumor size was not a prognostic factor for OS in mucinous and clear cell carcinoma.Conclusions: Our study suggest a markedly mortality rate in patients with stage IV mucinous and clear cell carcinoma, but better survival in patients with high-grade serous and endometrioid subtypes. Aggressive radical surgery to leave no residual disease would improve survival for high-grade serous and endometrioid carcinoma. More studies are needed to assess the value of aggressive radical surgery in patients with mucinous and clear cell subtypes