Mer Receptor Tyrosine Kinase Signaling: PREVENTION OF APOPTOSIS AND ALTERATION OF CYTOSKELETAL ARCHITECTURE WITHOUT STIMULATION OR PROLIFERATION

Mer is a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family, a family whose physiological function is not well defined. We constructed a Mer chimera using the epidermal growth factor receptor (EGFR) extracellular and transmembrane domains and the Mer cytoplasmic domain. Stable transfection of the Mer chimera into interleukin 3 (IL-3)-dependent murine 32D cells resulted in ligand-activable surface receptor that tyrosine autophosphorylated, stimulated intracellular signaling, and dramatically reduced apoptosis initiated by IL-3 withdrawal. However, unlike multiple other ectopically expressed receptor tyrosine kinases including full-length EGFR or an EGFR/Axl chimera, the Mer chimera did not stimulate proliferation. Moreover, and in contrast to EGFR, Mer chimera activation induced adherence and cell flattening in the normally suspension-growing 32D cells. The Mer chimera signal also blocked IL-3-dependent proliferation leading to G(1)/S arrest, dephosphorylation of retinoblastoma protein, and elongation of cellular processes. Unlike other agonists that lead to a slow (4-8 days) ligand-dependent differentiation of 32D cells, the combined Mer and IL-3 signal resulted in differentiated morphology and growth cessation in the first 24 h. Thus the Mer chimera blocks apoptosis without stimulating growth and produces cytoskeletal alterations; this outcome is clearly separable from the proliferative signal produced by most receptor tyrosine kinases

Variation of the Sterical Properties of the N-Heterocyclic Carbene Coligand in Thermally Triggerable Ruthenium-Based Olefin Metathesis Precatalysts/Initiators

A series of ruthenium complexes based on the kappa(2)( C,N) - (2- (benzo [h] quinolin-10-yl)methylidene ruthenium dichloride fragment featuring different neutral coligands L (L = 1,3-bis (2,6-diis opropylp henyl) -4, S- dihydroimidazol-2-ylidene (SIPr), 1,3-bis(2,4,6-trimethylpheny1)-4,5-dihydroimidazol-2-ylidene (SIMcs), 1,3-bis(2,4-dimethylpheny1)-4,5-dihydroimidazol-2-ylidene (81Xyl), and 1,3-bis(2-methylpheny1)4,5-dihydroimidazol-2-ylidene (SITO1)) was prepared, characterized, and tested in the thermally induced ring-opening metathesis polymerization of dicydopentadiene. In addition, the corresponding tricydohe#1phosphine derivative was investigated for comparison. All compounds were isolated as their trans-clichloro isomers. NMR spectroscopic features as well as structural features are, particularly within the NHC-bearing complexes, very similar, but their polymerization activity at elevated temperatures is distinctly different. While the SIMes derivatiie shows the desired properties, i.e., latency at room temperature and pronouneed polymerization activity at elevated temperature, 'all other preinitiators do not. The preinitiator featuring the SIPr coligarid is the most latent one, needing temperatures > 140 degrees C to show moderate: activity in the polymerization of dicydopentadiene. Compounds bearing the smaller N-heterocyclic carbene congeners are stable and latent at room temperature, but decompose upon heating, diminishing the polymerization activity at elevated temperatures. Density functional calculations show that the SIMes -derivative is the easiest to activate and yields the most stable 14-electron intermediate. Finally calculations reveal a distinct influence of the nature Of the N-heterocyclic carbene ligand on the position of the equilibrium of cis- and trans-dichloro isbrhers of the Complexes. -While the SLPr and the SIMes derivatives prefer the cisconfiguration, all other derivatives favor, at least in solvents with low dielectric constants, the trans-configuration. These computational findings were supported by the isolation and full characterization of the cis-dichloro isomer of the SIMes-bearing preinitiator obtained upon heating of its trans-isomer at 140 degrees C

Challenges and Opportunities in 3D Laser Printing Based on (1 + 1)-Photon Absorption

Most light-based 3D printing methods rely on optical or chemical nonlinearities to spatially confine the polymerization reaction. In 3D micro- and nanoprinting, this nonlinearity can be provided by two-photon absorption, which describes the simultaneous absorption of two photons. To achieve comparable absorption cross sections for two-photon as in one-photon absorption, short and intense laser pulses with intensities in the range of 1 TW/cm2 are typically required. Herein, we review three emerging excitation processes that provide a quadratic nonlinearity versus intensity without relying on two-photon absorption: upconversion luminescence, two-step absorption, and triplet-triplet annihilation. We term these “(1 + 1)-photon absorption”. Such processes allow for using continuous-wave lasers at much lower peak laser powers and at much lower cost than those typical for two-photon absorption. We review recent progress, describe current challenges, and outline future perspectives.</p