Search results for "translational"

Managerial practices driving knowledge creation, learning and transfer in translational research: an exploratory case study

2014

Despite its growing popularity in the biomedical literature, the particular phenomenon of translational research management has not been addressed from an organizational and strategic perspective yet. Our study aims to fill this gap by identifying a set of managerial practices that could influence how knowledge is created, amplified and transferred from biomedical research both to clinical practice and the productive sector. As a result of the theoretical review, we have proposed a preliminary model to guide our empirical work. We have developed an exploratory case study to gather organisational information from an outstanding translational research center. The results obtained from the ana…

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

2016

Background Ascending thoracic aortic aneurysm ( ATAA ) is driven by angiotensin II (Ang II ) and contributes to the development of left ventricular ( LV ) remodeling through aortoventricular coupling. We previously showed that locally available leptin augments Ang II ‐induced abdominal aortic aneurysms in apolipoprotein E–deficient mice. We hypothesized that locally synthesized leptin mediates Ang II ‐induced ATAA . Methods and Results Following demonstration of leptin synthesis in samples of human ATAA associated with different etiologies, we modeled in situ leptin expression in apolipoprotein E–deficient mice by applying exogenous leptin on the surface of the ascending aorta. This treatm…

eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ at the immune synapse by impairing actin binding to profilin-1.

2017

The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-¿ (PKC-¿) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of ß-actin and PKC-¿ from the lamellipodium-like distal (d)-SMAC, promoting PKC-¿ activation. Furthermore, eNOS-derived NO S-nitrosylated ß-…

Potassium-inhibited processing of IL-1 beta in human monocytes.

1995

Agents that deplete cells of K+ without grossly disrupting the plasma membrane were found to stimulate the cleavage of pro-interleukin (IL)-1 beta to mature IL-1 beta. Agents examined in this study included staphylococcal alpha-toxin and gramicidin, both of which selectively permeabilize plasma membranes for monovalent ions, the ionophores nigericin and valinomycin, and the Na+/K+ ATPase inhibitor ouabain. K+ depletion by brief hypotonic shock also triggered processing of pro-IL-1 beta. The central role of K+ depletion for inducing IL-1 beta maturation was demonstrated in cells permeabilized with alpha-toxin: processing of pro-IL-1 beta was totally blocked when cells were suspended in mediu…

FACIT collagen (1α-chain) is expressed by hemocytes and epidermis during the inflammatory response of the ascidian Ciona intestinalis

2007

Based on previous cloning and sequencing study, real-time PCR and in situ hybridization assays of the inflamed body wall of LPS-injected Ciona intestinalis showed the enhanced gene expression of a collagen with FACIT structural features (Ci-type IX-Col 1alpha-chain). By using specific antibodies raised against an opportunely chosen Ci-type IX-Col synthetic peptide, the fibroblast property of hemocytes challenged in vitro with LPS (at 4h) was displayed by flow cytometry, while immunocytochemistry identified hemocytes with large granules (morula cells) as collagen-producing cells. Hemocyte lysate supernatant analyzed in immunoblotting contained a 60 kDa band identifiable as 1alpha-chain-Ci-ty…

Targeted therapy of liver fibrosis/cirrhosis and its complications.

2011

Department of Pharmacokinetics, Toxicology, and Targeting, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA; Division of Molecular and Translational Medicine, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany

Anti-fibrotic therapy: lost in translation?

2012

While preclinical development of potential anti-fibrotics is far advanced, with numerous pharmacological targets and promising agents, almost none has entered clinical validation. Reasons are manifold, including the usually slow progression of liver fibrosis, requiring high numbers of well-stratified patients undergoing long-term treatment when conventional liver biopsy based parameters or hard liver-related endpoints are used. Importantly, there is a notorious lack of sensitive and specific surrogate markers or imaging technologies for liver fibrosis progression or regression that would permit a rapid clinical screening for potential anti-fibrotics. Nonetheless, in view of an urgent need f…

Stx5 is a novel interactor of VLDL-R to affect its intracellular trafficking and processing

2012

We identified syntaxin 5 (Stx5), a protein involved in intracellular vesicle trafficking, as a novel interaction partner of the very low density lipoprotein (VLDL)-receptor (VLDL-R), a member of the LDL-receptor family. In addition, we investigated the effect of Stx5 on VLDL-R maturation, trafficking and processing. Here, we demonstrated mutual association of both proteins using several in vitro approaches. Furthermore, we detected a special maturation phenotype of VLDL-R resulting from Stx5 overexpression. We found that Stx5 prevented advanced Golgi-maturation of VLDL-R, but did not cause accumulation of the immature protein in ER, ER to Golgi compartments, or cis-Golgi ribbon, the main ex…

Highlight on transient activation of red/ox-dependent survival signals involving MEK/ERK and PI3/Akt signaling pathways in 27-hydroxycholesterol trea…

2014

S-nitrosylation of the death receptor fas promotes fas ligand-mediated apoptosis in cancer cells.

2011

International audience; BACKGROUND & AIMS: Fas belongs to the family of tumor necrosis factor receptors which induce apoptosis. Many cancer cells express Fas but do not undergo Fas-mediated apoptosis. Nitric oxide reverses this resistance by increasing levels of Fas at the plasma membrane. We studied the mechanisms by which NO affects Fas function. METHODS: Colon and mammary cancer cell lines were incubated with the NO donor glyceryl trinitrate or lipid A; S-nitrosylation of Fas was monitored using the biotin switch assay. Fas constructs that contained mutations at cysteine residues that prevent S-nitrosylation were used to investigate the involvement of S-nitrosylation in Fas-mediated cell…