Browsing by Subject "In-vivo"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Open Access CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1(The American Society for Biochemistry and Molecular Biology, Inc., 2012) Ligons, D. L.; Tuncer, C.; Linowes, B. A.; Akcay, I. M.; Kurtulus, S.; Deniz, E.; Arslan, B. A.; Cevik, S. I.; Keller, H. R.; Luckey, M. A.; Feigenbaum, L.; Möröy, T.; Ersahin, T.; Atalay, R.; Erman, B.; Park, J. H.Interleukin-7 receptor α (IL-7Rα) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7Rα expression with diverse roles in T cell biology. Here we identify the transcriptional repressor, growth factor independent-1 (Gfi1), as a novel intermediary in glucocorticoid-induced IL-7Rα up-regulation. We found Gfi1 to be a major inhibitory target of dexamethasone by microarray expression profiling of 3B4.15 T-hybridoma cells. Concordantly, retroviral transduction of Gfi1 significantly blunted IL-7Rα up-regulation by dexamethasone. To further assess the role of Gfi1 in vivo, we generated bacterial artificial chromosome (BAC) transgenic mice, in which a modified Il7r locus expresses GFP to report Il7r gene transcription. By introducing this BAC reporter transgene into either Gfi1-deficient or Gfi1-transgenic mice, we document in vivo that IL-7Rα transcription is up-regulated in the absence of Gfi1 and down-regulated when Gfi1 is overexpressed. Strikingly, the in vivo regulatory role of Gfi1 was specific for CD8+, and not CD4+ T cells or immature thymocytes. These results identify Gfi1 as a specific transcriptional repressor of the Il7r gene in CD8 T lymphocytes in vivo.Item Open Access Nested metamaterials for wireless strain sensing(IEEE, 2009-12-28) Melik, R.; Unal, E.; Perkgoz, N. K.; Santoni, B.; Kamstock, D.; Puttlitz, C.; Demir, Hilmi VolkanWe designed, fabricated, and characterized metamaterial-based RF-microelectromechanical system (RF-MEMS) strain sensors that incorporate multiple split ring resonators (SRRs) in a compact nested architecture to measure strain telemetrically. We also showed biocompatibility of these strain sensors in an animal model. With these devices, our bioimplantable wireless metamaterial sensors are intended, to enable clinicians, to quantitatively evaluate the progression of long-bone fracture healing by monitoring the strain on the implantable fracture fixation hardware in real time. In operation, the transmission spectrum of the metamaterial sensor attached to the implantable fixture is changed when an external load is applied to the fixture, and from this change, the strain is recorded remotely. By employing telemetric characterizations, we reduced the operating frequency and enhanced the sensitivity of our novel nested SRR architecture compared to the conventional SRR structure. The nested SRR structure exhibited a higher sensitivity of 1.09 kHz/kgf operating at lower frequency compared to the classical SRR that demonstrated a sensitivity of 0.72 kHz/kgf. Using soft tissue medium, we achieved the best sensitivity level of 4.00 kHz/kgf with our nested SRR sensor. Ultimately, the laboratory characterization and in vivo biocompatibility studies support further development and characterization of a fracture healing system based on implantable nested SRR.Item Open Access p53 polymorphism influences response in cancer chemotheraphy via modulation of p73-dependent apoptosis(Elsevier, 2003-04) Bergamaschi, D.; Gasco, M.; Hiller, L.; Sullivan, A.; Syed, N.; Trigiante, G.; Yulug, I.; Merlano, M.; Numico, G.; Comino, A.; Attard, M.; Reelfs, O.; Gusterson, B.; Bell, A. K.; Heath, V.; Tavassoli, M.; Farrell, P. J.; Smith, P.; Lu, X.; Crook, T.Intact p73 function is shown to be an important determinant of cellular sensitivity to anticancer agents. Inhibition of p73 function by dominant-negative proteins or by mutant p53 abrogates apoptosis and cytotoxicity induced by these agents. A polymorphism encoding either arginine (72R) or proline (72P) at codon 72 of p53 influences inhibition of p73 by a range of p53 mutants identified in squamous cancers. Clinical response following cisplatin-based chemo-radiotherapy for advanced head and neck cancer is influenced by this polymorphism, cancers expressing 72R mutants having lower response rates than those expressing 72P mutants. Polymorphism in p53 may influence individual responsiveness to cancer therapy.