Adenomatous Polyposis Coli is Present Near the Minimal Level Required for Accurate Graded Responses to the Wingless Morphogen

The mechanisms by which the Wingless (Wg) morphogen modulates the activity of the transcriptional activator Armadillo (Arm) to elicit precise, concentration-dependent cellular responses remain uncertain. Arm is targeted for proteolysis by the Axin/Adenomatous polyposis coli (Apc1 and Apc2)/Zeste-white 3 destruction complex, and Wg-dependent inactivation of destruction complex activity is crucial to trigger Arm signaling. In the prevailing model for Wg transduction, only Axin levels limit destruction complex activity, whereas Apc is present in vast excess. To test this model, we reduced Apc activity to different degrees, and analyzed the effects on three concentration-dependent responses to Arm signaling that specify distinct retinal photoreceptor fates. We find that both Apc1 and Apc2 negatively regulate Arm activity in photoreceptors, but that the relative contribution of Apc1 is much greater than that of Apc2. Unexpectedly, a less than twofold reduction in total Apc activity, achieved by loss of Apc2, decreases the effective threshold at which Wg elicits a cellular response, thereby resulting in ectopic responses that are spatially restricted to regions with low Wg concentration. We conclude that Apc activity is not present in vast excess, but instead is near the minimal level required for accurate graded responses to the Wg morphogen

LiNbO3 acousto-optical and electro-optical micromodulators

We report on acousto-optical (AO) and electro-optical (EO) LiNbO3 modulators with an active length of only 11 µm. The miniature devices are based on photonic crystal (PhC) structures that are controlled by an external effect (DC electric field or Surface Acoustic Waves). Two processes are presented for realizing the PhCs despite the resistance of the material to etching. The first method is based on direct FIB writing and can yield the fabrication of holes with depth of 32 m and diameter of 12 m or less. The second method consists in FIB patterning of a mask which is deposited on the substrate. This process is followed by proton exchange (PE) and reactive ion etching (RIE). Thus, structures with a diameter of 400 nm and an aspect ratio of 3:1 have been fabricated. The methods have been applied to the fabrication of EO and AO micromodulators showing a driving voltage of 13,5 V and a driving electric power of 20 mW respectively. These developments open the way to dense integration of dynamic optical functionalities

Theoretical and experimental evidence of level repulsion states and evanescent modes in sonic crystal stubbed waveguides

The complex band structures calculated using the Extended Plane Wave Expansion (EPWE) reveal the presence of evanescent modes in periodic systems, never predicted by the classical \omega(\vec{k}) methods, providing novel interpretations of several phenomena as well as a complete picture of the system. In this work we theoretically and experimentally observe that in the ranges of frequencies where a deaf band is traditionally predicted, an evanescent mode with the excitable symmetry appears changing drastically the interpretation of the transmission properties. On the other hand, the simplicity of the sonic crystals in which only the longitudinal polarization can be excited, is used to interpret, without loss of generality, the level repulsion between symmetric and antisymmetric bands in sonic crystals as the presence of an evanescent mode connecting both repelled bands. These evanescent modes, obtained using EPWE, explain both the attenuation produced in this range of frequencies and the transfer of symmetry from one band to the other in good agreement with both experimental results and multiple scattering predictions. Thus, the evanescent properties of the periodic system have been revealed necessary for the design of new acoustic and electromagnetic applications based on periodicity

The E3 ubiquitin ligase component, Cereblon, is an evolutionarily conserved regulator of Wnt signaling

Immunomodulatory drugs (IMiDs) are important for the treatment of multiple myeloma and myelodysplastic syndrome. Binding of IMiDs to Cereblon (CRBN), the substrate receptor of the CRL4CRBN E3 ubiquitin ligase, induces cancer cell death by targeting key neo-substrates for degradation. Despite this clinical significance, the physiological regulation of CRBN remains largely unknown. Herein we demonstrate that Wnt, the extracellular ligand of an essential signal transduction pathway, promotes the CRBN-dependent degradation of a subset of proteins. These substrates include Casein kinase 1α (CK1α), a negative regulator of Wnt signaling that functions as a key component of the β-Catenin destruction complex. Wnt stimulation induces the interaction of CRBN with CK1α and its resultant ubiquitination, and in contrast with previous reports does so in the absence of an IMiD. Mechanistically, the destruction complex is critical in maintaining CK1α stability in the absence of Wnt, and in recruiting CRBN to target CK1α for degradation in response to Wnt. CRBN is required for physiological Wnt signaling, as modulation of CRBN in zebrafish and Drosophila yields Wnt-driven phenotypes. These studies demonstrate an IMiD-independent, Wnt-driven mechanism of CRBN regulation and provide a means of controlling Wnt pathway activity by CRBN, with relevance for development and disease

Conductive Cellulose Composites with Low Percolation Threshold for 3D Printed Electronics

We are reporting a 3D printable composite paste having strong thixotropic rheology. The composite has been designed and investigated with highly conductive silver nanowires. The optimized electrical percolation threshold from both simulation and experiment is shown from 0.7 vol. % of silver nanowires which is significantly lower than other composites using conductive nano-materials. Reliable conductivity of 1.19 × 102 S/cm has been achieved from the demonstrated 3D printable composite with 1.9 vol. % loading of silver nanowires. Utilizing the high conductivity of the printable composites, 3D printing of designed battery electrode pastes is demonstrated. Rheology study shows superior printability of the electrode pastes aided by the cellulose\u27s strong thixotropic rheology. The designed anode, electrolyte, and cathode pastes are sequentially printed to form a three-layered lithium battery for the demonstration of a charging profile. This study opens opportunities of 3D printable conductive materials to create printed electronics with the next generation additive manufacturing process

Caenorhabditis elegans SMA-10/LRIG Is a Conserved Transmembrane Protein that Enhances Bone Morphogenetic Protein Signaling

Bone morphogenetic protein (BMP) pathways control an array of developmental and homeostatic events, and must themselves be exquisitely controlled. Here, we identify Caenorhabditis elegans SMA-10 as a positive extracellular regulator of BMP–like receptor signaling. SMA-10 acts genetically in a BMP–like (Sma/Mab) pathway between the ligand DBL-1 and its receptors SMA-6 and DAF-4. We cloned sma-10 and show that it has fifteen leucine-rich repeats and three immunoglobulin-like domains, hallmarks of an LRIG subfamily of transmembrane proteins. SMA-10 is required in the hypodermis, where the core Sma/Mab signaling components function. We demonstrate functional conservation of LRIGs by rescuing sma-10(lf) animals with the Drosophila ortholog lambik, showing that SMA-10 physically binds the DBL-1 receptors SMA-6 and DAF-4 and enhances signaling in vitro. This interaction is evolutionarily conserved, evidenced by LRIG1 binding to vertebrate receptors. We propose a new role for LRIG family members: the positive regulation of BMP signaling by binding both Type I and Type II receptors