Cell-type specific potent Wnt signaling blockade by bispecific antibody.

Cell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/β-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity. We found that the bispecific antibody inhibits Wnt-induced reporter activities with over one hundred-fold enhancement in potency, and in a cell type-selective manner. Potency enhancement is dependent on the expression level of the guide antigen on the target cell surface and the apparent affinity of the anti-guide antibody. Both internalizing and non-internalizing guide antigens can be used, with internalizing bispecific antibody being able to block signaling by all ligands binding to the target receptor due to its removal from the cell surface. It is thus feasible to develop bispecific-based therapeutic strategies that potently and selectively inhibit signaling pathways in a cell type-selective manner, creating opportunity for therapeutic targeting

Elastocapillary driven assembly of particles at free-standing smectic-A films

Colloidal particles at complex fluid interfaces and within films assemble to form ordered structures with high degrees of symmetry via interactions that include capillarity, elasticity, and other fields like electrostatic charge. Here we study microparticle interactions within free-standing smectic-A films, in which the elasticity arising from the director field distortion and capillary interactions arising from interface deformation compete to direct the assembly of motile particles. New colloidal assemblies and patterns, ranging from 1D chains to 2D aggregates, sensitive to the initial wetting conditions of particles at the smectic film, are reported. This work paves the way to exploiting LC interfaces as a means to direct spontaneously formed, reconfigurable, and optically active materials.Comment: 8 pages, 6 figures. Supplementary Materials: 3 pages, 3 figure

Chandra View of DA 530: A Sub-Energetic Supernova Remnant with a Pulsar Wind Nebula?

Based on a Chandra ACIS observation, we report the detection of an extended X-ray feature close to the center of the remnant DA 530 with 5.3 sigma above the background within a circle of 20'' radius. This feature, characterized by a power-law with the photon index gamma=1.6+-0.8 and spatially coinciding with a nonthermal radiosource, most likely represents a pulsar wind nebula. We have further examined the spectrum of the diffuse X-ray emission from the remnant interior with a background-subtracted count rate of ~0.06 counts s^-1 in 0.3-3.5 keV. The spectrum of the emission can be described by a thermal plasma with a temperature of ~0.3-0.6 keV and a Si over-abundance of >~7 solar. These spectral characteristics, together with the extremely low X-ray luminosity, suggest that the remnant arises from a supernova with an anomalously low mechanical energy (<10^50 ergs). The centrally-filled thermal X-ray emission of the remnant may indicate an early thermalization of the SN ejecta by the circum-stellar medium. Our results suggest that the remnant is likely the product of a core-collapsed SN with a progenitor mass of 8-12 Msun. Similar remnants are probably common in the Galaxy, but have rarely been studied.Comment: 23 pages, 7 figures, accepted for publication in ApJ; complete the abstract on astro-ph and correct some typo