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Full-Text Articles in Life Sciences

A Genetically Encoded Fluorescent Sensor Of Erk Activity, Christopher D. Harvey, Anka G. Ehrhardt, Cristina Arrigo Cellurale, Haining Zhong, Ryohei Yasuda, Roger J. Davis, Karel Svoboda Dec 2008

A Genetically Encoded Fluorescent Sensor Of Erk Activity, Christopher D. Harvey, Anka G. Ehrhardt, Cristina Arrigo Cellurale, Haining Zhong, Ryohei Yasuda, Roger J. Davis, Karel Svoboda

Davis Lab Publications

The activity of the ERK has complex spatial and temporal dynamics that are important for the specificity of downstream effects. However, current biochemical techniques do not allow for the measurement of ERK signaling with fine spatiotemporal resolution. We developed a genetically encoded, FRET-based sensor of ERK activity (the extracellular signal-regulated kinase activity reporter, EKAR), optimized for signal-to-noise ratio and fluorescence lifetime imaging. EKAR selectively and reversibly reported ERK activation in HEK293 cells after epidermal growth factor stimulation. EKAR signals were correlated with ERK phosphorylation, required ERK activity, and did not report the activities of JNK or p38. EKAR reported ERK ...


Percutaneous Transendocardial Delivery Of Self-Complementary Adeno-Associated Virus 6 Achieves Global Cardiac Gene Transfer In Canines, Lawrence T. Bish, Meg M. Sleeper, Benjamin Brainard, Stephen Cole, Nicholas Russell, Elanor Withnall, Jason Arndt, Caryn Reynolds, Ellen Davison, Julio Sanmiguel, Di Wu, Guangping Gao, James M. Wilson, H Lee Sweeney Dec 2008

Percutaneous Transendocardial Delivery Of Self-Complementary Adeno-Associated Virus 6 Achieves Global Cardiac Gene Transfer In Canines, Lawrence T. Bish, Meg M. Sleeper, Benjamin Brainard, Stephen Cole, Nicholas Russell, Elanor Withnall, Jason Arndt, Caryn Reynolds, Ellen Davison, Julio Sanmiguel, Di Wu, Guangping Gao, James M. Wilson, H Lee Sweeney

Open Access Articles

Achieving efficient cardiac gene transfer in a large animal model has proven to be technically challenging. Previous strategies have used cardiopulmonary bypass or dual catheterization with the aid of vasodilators to deliver vectors, such as adenovirus, adeno-associated virus (AAV), or plasmid DNA. Although single-stranded AAV (ssAAV) vectors have shown the greatest promise, they suffer from delayed expression, which might be circumvented using self-complementary vectors. We sought to optimize cardiac gene transfer using a percutaneous transendocardial injection catheter to deliver adeno-associated viral vectors to the canine myocardium. Four vectors were evaluated-ssAAV9, self-complementary AAV9 (scAAV9), scAAV8, scAAV6-so that comparison could be made ...


Jun N-Terminal Kinase 1 Regulates Epithelial-To-Mesenchymal Transition Induced By Tgf-Beta1, John F. Alcorn, Amy S. Guala, Jos Van Der Velden, Brian Mcelhinney, Charles G. Irvin, Roger J. Davis, Yvonne M.W. Janssen-Heininger Apr 2008

Jun N-Terminal Kinase 1 Regulates Epithelial-To-Mesenchymal Transition Induced By Tgf-Beta1, John F. Alcorn, Amy S. Guala, Jos Van Der Velden, Brian Mcelhinney, Charles G. Irvin, Roger J. Davis, Yvonne M.W. Janssen-Heininger

Davis Lab Publications

Transforming growth factor beta1 (TGF-beta1) is a cardinal cytokine in the pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal transition (EMT). As a molecular interaction between TGF-beta1 and Jun N-terminal kinase (JNK) has been demonstrated, the goal of this study was to elucidate whether JNK plays a role in TGF-beta1-induced EMT. Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were comparatively evaluated for their ability to undergo EMT in response to TGF-beta1. Wild-type MTEC exposed to TGF-beta1 demonstrated a prominent induction of mesenchymal mediators and a loss of epithelial markers, in conjunction with a loss ...


C-Jun Nh2-Terminal Kinase 2 Inhibits Gamma Interferon Production During Anaplasma Phagocytophilum Infection, Joao H.F. Pedra, Jochen Mattner, Jian Tao, Steven M. Kerfoot, Roger J. Davis, Richard A. Flavell, Philip W. Askenase, Zhinan Yin, Erol Fikrig Jan 2008

C-Jun Nh2-Terminal Kinase 2 Inhibits Gamma Interferon Production During Anaplasma Phagocytophilum Infection, Joao H.F. Pedra, Jochen Mattner, Jian Tao, Steven M. Kerfoot, Roger J. Davis, Richard A. Flavell, Philip W. Askenase, Zhinan Yin, Erol Fikrig

Davis Lab Publications

Gamma interferon (IFN-gamma) plays a critical role in the early eradication of Anaplasma phagocytophilum. However, the mechanisms that regulate IFN-gamma production upon infection remain poorly understood. Here we show that c-Jun NH2-terminal kinase 2 (JNK2) inhibits IFN-gamma production during A. phagocytophilum infection. jnk2-null mice were more refractory to infection with A. phagocytophilum and produced increased levels of IFN-gamma after challenge with the pathogen. The resistance of jnk2-null mice to A. phagocytophilum infection was due to elevated levels of IFN-gamma secreted by conventional and natural killer (NK) T cells. The administration of alpha-galactosylceramide, a strong NK T-cell agonist, increased IFN-gamma release ...