46 research outputs found
Mutational Analysis of Hedgehog Signaling Pathway Genes in Human Malignant Mesothelioma
Background
The Hedgehog (HH) signaling pathway is critical for embryonic development and adult homeostasis. Recent studies have identified regulatory roles for this pathway in certain cancers with mutations in the HH pathway genes. The extent to which mutations of the HH pathway genes are involved in the pathogenesis of malignant mesothelioma (MMe) is unknown.
Methodology/Principal Findings
Real-time PCR analysis of HH pathway genes PTCH1, GLI1 and GLI2 were performed on 7 human MMe cell lines. Exon sequencing of 13 HH pathway genes was also performed in cell lines and human MMe tumors. In silico programs were used to predict the likelihood that an amino-acid substitution would have a functional effect. GLI1, GLI2 and PTCH1 were highly expressed in MMe cells, indicative of active HH signaling. PTCH1, SMO and SUFU mutations were found in 2 of 11 MMe cell lines examined. A non-synonymous missense SUFU mutation (p.T411M) was identified in LO68 cells. In silico characterization of the SUFU mutant suggested that the p.T411M mutation might alter protein function. However, we were unable to demonstrate any functional effect of this mutation on Gli activity. Deletion of exons of the PTCH1 gene was found in JU77 cells, resulting in loss of one of two extracellular loops implicated in HH ligand binding and the intracellular C-terminal domain. A 3-bp insertion (69_70insCTG) in SMO, predicting an additional leucine residue in the signal peptide segment of SMO protein was also identified in LO68 cells and a MMe tumour.
Conclusions/Significance
We identified the first novel mutations in PTCH1, SUFU and SMO associated with MMe. Although HH pathway mutations are relatively rare in MMe, these data suggest a possible role for dysfunctional HH pathway in the pathogenesis of a subgroup of MMe and help rationalize the exploration of HH pathway inhibitors for MMe therapy
Mechanical characteristics of fiber-filled photo-polymer used in stereolithography
Rapid Prototyping Journal53112-119RPJO
Influence of process parameters on stereolithography part shrinkage
Materials and Design174205-21
Constructing Hierarchical Spheres from Large Ultrathin Anatase TiO2 Nanosheets with Nearly 100% Exposed (001) Facets for Fast Reversible Lithium Storage
Synthesis of nanocrystals with exposed high-energy facets is a well-known
challenge in many fields of science and technology. The higher reactivity of these facets
simultaneously makes them desirable catalysts for sluggish chemical reactions and leads
to their small populations in an equilibrated crystal. Using anatase TiO2 as an example,
we demonstrate a facile approach for creating high surface area, stable nanosheets
comprised of nearly 100% exposed (001) facets. Our approach relies on spontaneous
assembly of the nanosheets into three-dimensional, hierarchical spheres that stabilizes
them from collapse. We show that the high surface density of exposed TiO2 (001) facets
leads to fast lithium insertion/deinsertion processes in batteries that mimic features seen
in high power electrochemical capacitors.X.W.L. and L.A.A. acknowledge support
from Award KUS-C1-018-02 made by King Abdullah University
of Science and Technology (KAUST). The authors are grateful
to the reviewers and Prof. Hua Chun Zeng (National University
of Singapore) for very valuable comments and to Nanyang
Technological University for financial support through a startup
grant (SUG)