Transcriptional adaptations to hypoxia are mediated by hypoxia-inducible factor (HIF)-1, a heterodimer of HIF-␣ and aryl hydrocarbon receptor nuclear translocator subunits. The HIF-1␣ and HIF-2␣ subunits both undergo rapid hypoxia-induced protein stabilization and bind identical target DNA sequences. When coexpressed in similar cell types, discriminating control mechanisms may exist for their regulation, explaining why HIF-1␣ and HIF-2␣ do not substitute during embryogenesis. We report that, in a human lung epithelial cell line (A549), HIF-1␣ and HIF-2␣ proteins were similarly induced by acute hypoxia (4 h, 0.5% O 2 ) at the translational or posttranslational level. However, HIF-1␣ and HIF-2␣ were differentially regulated by prolonged hypoxia (12 h, 0.5% O 2 ) since HIF-1␣ protein stimulation disappeared because of a reduction in its mRNA stability, whereas HIF-2␣ protein stimulation remained high and stable. Prolonged hypoxia also induced an increase in the quantity of natural antisense HIF-1␣ (aHIF), whose gene promoter contains several putative hypoxia response elements to which (as we confirm here) the HIF-1␣ or HIF-2␣ protein can bind. Finally, transient transfection of A549 cells by dominant-negative HIF-2␣, also acting as a dominant-negative for HIF-1␣, prevented both the decrease in the HIF-1␣ protein and the increase in the aHIF transcript. Taken together, these data indicate that, during prolonged hypoxia, HIF-␣ proteins negatively regulate HIF-1␣ expression through an increase in aHIF and destabilization of HIF-1␣ mRNA. This transregulation between HIF-1␣ and HIF-2␣ during hypoxia likely conveys target gene specificity.
Inkjet printing is emerging at the forefront of biosensor fabrication technologies. Parallel advances in both ink chemistry and printers have led to a biosensor manufacturing approach that is simple, rapid, flexible, high resolution, low cost, efficient for mass production, and extends the capabilities of devices beyond other manufacturing technologies. Here we review for the first time the factors behind successful inkjet biosensor fabrication, including printers, inks, patterning methods, and matrix types. We discuss technical considerations that are important when moving beyond theoretical knowledge to practical implementation. We also highlight significant advances in biosensor functionality that have been realised through inkjet printing. Finally, we consider future possibilities for biosensors enabled by this novel combination of chemistry and technology.
The aggregation process of a two-component dilute system (3 vol %), made of alumina submicrometer particles and silica nanoparticles, is studied by Brownian dynamics simulations. Alumina and silica particles have very different sizes (diameters of 400 and 25 nm, respectively). The particle-particle interaction potential is of the DLVO form. The parameters of the potential are extracted from the experiments. The simulations show that the experimentally observed aggregation phenomena between alumina particles are due to the silica-alumina attraction that induces an effective driving force for alumina-alumina aggregation. The experimental data for silica adsorption on alumina are very well reproduced.
Long term stability of ceramics at high temperatures is one of the great challenges of the contemporary technology developments. Multi‐component ceramics such as Si–B–C–N systems gain a lot of interest for high temperature applications due to the stability of their amorphous inorganic network arising from strong covalent bonding. The polymer derived ceramics (PDC) route enables the synthesis of such materials from preceramic polymers as well as their manufacturing as specific ceramic geometries, which are difficult to obtain otherwise. This review proposes an overview of the works related to the development of Si–B–C–N ceramics through the PDC route in the last 30 years. A particular focus is made on the relation between the chemical structure of the precursors and the properties of the resulting ceramics. The main topics reviewed are related to the synthesis of tailor‐made polymeric precursors, to their processing to ceramic components, and to the characterization of the material properties and functionalities. The various strategies adopted for the development of shaped Si–B–C–N ceramics as functional materials are presented and the trend of nowadays research for future evolution of Si–B–C–N materials is discussed.
Nanocrystalline apatites analogous to bone mineral are very promising materials for the preparation of highly bioactive ceramics due to their unique intrinsic physico-chemical characteristics. Their surface reactivity is indeed linked to the presence of a metastable hydrated layer on the surface of the nanocrystals. Yet the sintering of such apatites by conventional techniques, at high temperature, strongly alters their physico-chemical characteristics and biological properties, which points out the need for "softer" sintering processes limiting such alterations. In the present work a non-conventional technique, spark plasma sintering, was used to consolidate such nanocrystalline apatites at non-conventional, very low temperatures (T<300 degrees C) so as to preserve the surface hydrated layer present on the nanocrystals. The bioceramics obtained were then thoroughly characterized by way of complementary techniques. In particular, microstructural, nanostructural and other major physico-chemical features were investigated and commented on. This work adds to the current international concern aiming at improving the capacities of present bioceramics, in view of elaborating a new generation of resorbable and highly bioactive ceramics for bone tissue engineering.
BackgroundHypoxia-inducible factor-1α (HIF-1α) is part of a transcriptional factor that regulates genes involved in metabolic and vascular adaptation of tumours to oxygen restriction. A splicing variant lacking exon 14 (sHIF-1α) encodes a truncated protein that competes with the normal HIF-1α protein, decreasing its activity. A natural antisense transcript (aHIF) complementary to the 3'-untranslated region of HIF-1α mRNA was described recently.MethodsWith a semiquantitative multiplex reverse transcriptase–PCR (RT–PCR) assay, we assessed transcript concentrations of HIF-1α, sHIF-1α and aHIF in 110 patients with invasive breast carcinoma.ResultsWe found a strong positive association between HIF-1α and sHIF-1α, sHIF-1α and aHIF, and an inverse correlation between HIF-1α /sHIF-1α and aHIF. aHIF transcript expression was associated with poor disease-free survival in univariate (P = 0.0038) and multivariate (P = 0.0016) analyses in this series of high-risk primary breast carcinomas.ConclusionIn our series of breast cancer patients, aHIF, and not HIF-1α transcript, is a marker of poor prognosis.
Use of bone trocar to create a hole in the muscular process of the arytenoid cartilage for suture passage in laryngoplasty may reduce fissure formation and decrease the risk of cartilage failure from suture pullout.
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