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Deciphering The Mechanism Of O2 Reduction With Electronically Tunable Non-Heme Iron Enzyme Model Complexes, Roshaan Surendhran, Alexander A. D'Arpino, Bao Y. Sciscent, Anthony F. Cannella, Alan E. Friedman, Samantha N. Macmillan, Rupal Gupta, David C. Lacy

Publications and Research

A homologous series of electronically tuned 2,20,200-nitrilotris(N-arylacetamide) pre-ligands (H3LR) were prepared (R ¼ NO2, CN, CF3, F, Cl, Br, Et, Me, H, OMe, NMe2) and some of their corresponding Fe and Zn species synthesized. The iron complexes react rapidly with O2, the final products of which are diferric mu-oxo bridged species. The crystal structure of the oxidized product obtained from DMA solutions contain a structural motif found in some diiron proteins. The mechanism of iron mediated O2 reduction was explored to the extent that allowed us to construct an empirically consistent rate law. A Hammett plot was constructed that enabled …

Monitoring The Progression Of Spontaneous Articular Cartilage Healing With Infrared Spectroscopy, Megan P. O'Brien, Madhuri Penmatsa, Uday Palukuru, Paul West, Xu Yang, Mathias P. G. Bostrom, Theresa Freeman, Nancy Pleshko

Publications and Research

Objective. Evaluation of early compositional changes in healing articular cartilage is critical for understanding tissue repair and for therapeutic decision-making. Fourier transform infrared imaging spectroscopy (FT-IRIS) can be used to assess the molecular composition of harvested repair tissue. Furthermore, use of an infrared fiber-optic probe (IFOP) has the potential for translation to a clinical setting to provide molecular information in situ. In the current study, we determined the feasibility of IFOP assessment of cartilage repair tissue in a rabbit model, and assessed correlations with gold-standard histology.

Design. Bilateral osteochondral defects were generated in mature white New Zealand rabbits, and …

Dynamic Gene Expression In The Human Cerebral Cortex Distinguishes Children From Adults, Kirstin N. Sterner, Amy Weckle, Harry T. Chugani, Adi L. Tarca, Chet C. Sherwood, Patrick R. Hof, Christopher W. Kuzawa, Amy M. Boddy, Asad Abbas, Ryan L. Raaum, Lucie Grégoire, Leonard Lipovich, Lawrence I. Grossman, Monica Uddin, Morris Goodman, Derek E. Wildman

Publications and Research

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR>0). Moreover, genes known to …

Nongenomic Mechanisms Of Pten Regulation, Jimmie E. Fata, Shawon Debnath, Edmund C. Jenkins, Marcia V. Fournier

Publications and Research

A large amount of data supports the view that PTEN is a bona fide tumor suppressor gene. However, recent evidence suggests that derailment of cellular localization and expression levels of functional nonmutated PTEN is a determining force in inducing abnormal cellular and tissue outcomes. As the cellular mechanisms that regulate normal PTEN enzymatic activity resolve, it is evident that deregulation of these mechanisms can alter cellular processes and tissue architecture and ultimately lead to oncogenic transformation. Here we discuss PTEN ubiquitination, PTEN complex formation with components of the adherens junction, PTEN nuclear localization, and microRNA regulation of PTEN as essential …