New Role For Hpar-1 Kinases Emk And C-Tak1 In Regulating Localization And Activity Of Class Iia Histone Deacetylases

in Molecular and Cellular Biology (2006), 26(19), 7086-102

Class IIa histone deacetylases (HDACs) are found both in the cytoplasm and in the nucleus where they repress genes involved in several major developmental programs. In response to specific signals, the ... [more ▼]

Class IIa histone deacetylases (HDACs) are found both in the cytoplasm and in the nucleus where they repress genes involved in several major developmental programs. In response to specific signals, the repressive activity of class IIa HDACs is neutralized through their phosphorylation on multiple N-terminal serine residues and 14-3-3-mediated nuclear exclusion. Here, we demonstrate that class IIa HDACs are subjected to signal-independent nuclear export that relies on their constitutive phosphorylation. We identify EMK and C-TAK1, two members of the microtubule affinity-regulating kinase (MARK)/Par-1 family, as regulators of this process. We further show that EMK and C-TAK1 phosphorylate class IIa HDACs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function. Using HDAC7 as a paradigm, we extend these findings by demonstrating that signal-independent phosphorylation of the most N-terminal serine residue by the MARK/Par-1 kinases, i.e., Ser155, is a prerequisite for the phosphorylation of the nearby 14-3-3 site, Ser181. We propose that this multisite hierarchical phosphorylation by a variety of kinases allows for sophisticated regulation of class IIa HDACs function. [less ▲]

A new role for the PP2A regulatory subunit Balpha in angiogenesis

Conference (2010)

A New Route for the Synthesis of [18f]Fluoroaromatic Substituted Amino Acids: No Carrier Added L-P-[18f]Fluorophenylalanine

in International Journal of Radiation Applications and Instrumentation. Part A : Applied Radiation and Isotopes (1987), 38(12), 1033-8

L-p-[18F]fluorophenylalanine was designed as a potential marker for probing protein synthesis in the human brain by positron emission tomography. This radiotracer has been synthesized using nucleophilic ... [more ▼]

L-p-[18F]fluorophenylalanine was designed as a potential marker for probing protein synthesis in the human brain by positron emission tomography. This radiotracer has been synthesized using nucleophilic displacement of the activated nitro group of p-nitrobenzaldehyde by NCA 18F- obtained from the 18O (p, n) reaction on enriched water. The L-form of the [18F]fluoroamino acid can be separated on an analytical scale chiral column. A typical production run of 22.2 GBq (600 mCi) of 18F obtained after a 10 microA.h bombardment of 18 MeV protons on 99.8% 18O-enriched water leads to a batch of 1.11 GBq (30 mCi) of NCA L-p-[18F]fluorophenylalanine after a total synthesis time of 120 min. [less ▲]

New ruthenium catalysts bearing N-heterocyclic carbene ligands for ATRA and ATRP

in e-polymers (2003)

This study provides a glimpse of the synthetic possibilities arising from the use of NHC􀀀 s complexes in radical reactions, and illustrates how the fine tuning of the steric and electronic parameters of ... [more ▼]

This study provides a glimpse of the synthetic possibilities arising from the use of NHC􀀀 s complexes in radical reactions, and illustrates how the fine tuning of the steric and electronic parameters of this class of ruthenium complexes affect their catalytic activity. [less ▲]

New ruthenium catalysts bearing N-heterocyclic carbene ligands for ATRP

Poster (2003, May)

Stable nucleophilic N-heterocyclic carbenes (NHCs) are neutral, two-electron ligands with a negligible p-back-bonding tendency. They behave as phosphine mimics, yet they are better s- donors and they form ... [more ▼]

Stable nucleophilic N-heterocyclic carbenes (NHCs) are neutral, two-electron ligands with a negligible p-back-bonding tendency. They behave as phosphine mimics, yet they are better s- donors and they form stronger bonds to metal centers than most phosphines. Their electronic and steric properties are liable to ample modification simply by varying the substituents on the nitrogen atoms. Therefore, NHCs constitute a promising new class of ligands available for catalyst engineering and fine-tuning. We found that the 18-electron complex RuCl2(p-cymene)(PCy3) was a versatile and efficient promoter for ring-opening metathesis polymerization of both strained and low-strain cyclic olefins when activated by a suitable precursor such as trimethylsilyldiazomethane. This complex was also an excellent catalyst for ATRP (Atom Transfer Radical Polymerization) of MMA and styrene. In this poster, we present preliminary results obtained in olefin metathesis and in radical reactions (ATRP and Kharasch addition) when tricyclohexylphosphine was substituted by an N-heterocylic carbene ligand. [less ▲]

The "New Science" and the Sea - Academies, Learned Societies and Marine Knowledge in the Seventeenth and Eighteenth Centuries

Conference (2012, July 05)

Academies and learned societies were the main tools for the application of the “new science” in the seventeenth and eighteenth centuries. This paper aims to contribute to the research on marine science ... [more ▼]

Academies and learned societies were the main tools for the application of the “new science” in the seventeenth and eighteenth centuries. This paper aims to contribute to the research on marine science, nautical knowledge and empire building by studying academies and learned societies in their role of bureaus of investigation of the colonial reality. As a fact, institutions such as the Académie Royale des Sciences in Paris and the Royal Society of London played an important role as mediators in the development of various models of “science policies”. This paper focuses on the implication of these institutions in overseas scientific exploration in the seventeenth and eighteenth centuries. It stresses the specific importance of “academic” voyages for the development of navigational techniques, from Huygens and Hooke to Maskelyne and Harrison. This comparative study thus tries to show how through these new centers of knowledge production a scholarly interest for day-to-day nautical practices influenced the scientized perfection of navigational techniques. [less ▲]

A New Separable Approximation Scheme for Topological Problems and Optimization Problems Characterized by a Large Number of Design Variables

in Olhoff, Niels; Rozvany, Georges I.N. (Eds.) Proceedings of the First World Congress of Structural and Multidisciplinary Optimization (WCSMO1) (1995, May)

This paper is dedicated to a new convex separable approximation for solving optimization problems characterized by a very large number of design variables as in topology design. For such problems, the ... [more ▼]

This paper is dedicated to a new convex separable approximation for solving optimization problems characterized by a very large number of design variables as in topology design. For such problems, the convergence speed can be accelerated if one uses high quality approximation schemes for structural responses. To achieve this task, we propose, here, a new approximation procedure that belongs to the GMMA family. The originality of this new scheme is to rely on an automatic selection procedure of the asymptotes, using only first and zero order information accumulated during the previous iterations. This is possible owing to a diagonal Quasi-Newton update technique. Firstly, the new approximation procedure is validated on classical "benchmarks" of structural optimization. Then, it is compared to other schemes on a typical topology optimization problem. [less ▲]

New serum biochemical markers (Coll 2-1 and Coll 2-1 NO2) for studying oxidative-related type II collagen network degradation in patients with osteoarthritis and rheumatoid arthritis

in Osteoarthritis and Cartilage (2005), 13(3), 258-265

Objective: Protein nitration is a prominent feature of inflammatory processes in the joint. We have developed immunoassays specific for a peptide of the alpha-helical region of type II collagen (108 ... [more ▼]

Objective: Protein nitration is a prominent feature of inflammatory processes in the joint. We have developed immunoassays specific for a peptide of the alpha-helical region of type II collagen (108)HRGYPGLDG(116) (Coll 2-1) and its nitrated form (108)HRGY(NO2)PGLDG(116) (Coll 2-1 NO2) in biological fluids. Design: Coll 2-1 and Coll 2-1 NO2 peptides were injected into rabbits. Two antisera (D3 and D37) were selected for their specificity and affinity and used to develop specific immunoassays. Coll 2-1 and Coll 2-1 NO2 were measured in sera of 242 healthy subjects (N), 67 patients with primary knee osteoarthritis (OA) and 19 patients with rheumatoid arthritis (RA). Results: In healthy subjects, Coll 2-1 and Coll 2-1 NO2 concentrations were 125.13 +/- 3.71 nM and 0.16 +/- 0.08 nM, respectively. In OA and RA, Coll 2-1 and Coll 2-1 NO2 serum levels were found to be significantly increased compared to controls of the same range of age (Coll 2-1: OA: 200.80 +/- 8.98 nM, RA: 172.30 +/- 19.05 nM, normal: 126.60 +/- 6.70 nM and Coll 2-1 NO2: OA: 0.26 +/- 0.02, RA: 0.38 +/- 0.05, normal: 0.12 +/- 0.01 nM). Coll 2-1 NO2 levels were significantly more elevated in RA than in OA patients (P < 0.05). As a consequence, the ratio Coll 2-1 NO2/Coll 2-1 was 1.6 times higher in RA than in OA subjects. No relationship was found between the radiological OA severity and the levels of Coll 2-1 and Coll 2-1 NO2 in serum. Coll 2-1 NO2, but not Coll 2-1, was correlated with C-reactive protein in the sera of OA and RA patients. Conclusions: The determination of both Coll 2-1 and Coll 2-1 NO2 in serum of arthritic patients seems to be a promising useful tool for the detection of oxidative-related cartilage degradation episode. Further, these markers could be helpful for monitoring the effects of anti-inflammatory or antioxidant drugs on cartilage degradation. (c) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. [less ▲]

A New Shift-Share Method

E-print/Working paper (2012)

New silica based polymeric systems designed for the solid-liquid extraction of uranyl ions

in Journal of Materials Chemistry (2002), 12