Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C.

VLGR1 (very large G protein-coupled receptor 1), also known as MASS1 (monogenic audiogenic seizure susceptible 1), is an orphan G protein-coupled receptor that contains a large extracellular N terminus with 35 calcium-binding domains. A truncating mutation in the Mass1 gene causes autosomal recessive, sound-induced seizures in the Frings mouse. However, the function of MASS1 and the mechanism underlying Frings mouse epilepsy are not known. Here, we found that MASS1 protein is enriched in the myelinated regions of the superior and inferior colliculi, critical areas for the initiation and propagation of audiogenic seizures. Using a panel of myelin antibodies, we discovered that myelin-associated glycoprotein (MAG) expression is dramatically decreased in Frings mice. MASS1 inhibits the ubiquitylation of MAG, thus enhancing the stability of this protein, and the calcium-binding domains of MASS1 are essential for this regulation. Furthermore, MASS1 interacts with Gαs/Gαq and activates PKA and PKC in response to extracellular calcium. Suppression of signaling by MASS1 RNAi or a specific inhibitor abrogates MAG up-regulation. We postulate that MASS1 senses extracellular calcium and activates cytosolic PKA/PKC pathways to regulate myelination by means of MAG protein stability in myelin-forming cells of the auditory pathway. Further work is required to determine whether MAG dysregulation is a cause or consequence of audiogenic epilepsy and whether there are other pathways regulated by MASS1

Expanding Group Support System Capabilities from the Knowledge Management Perspective

A group support system (GSS) is a computer-based system that enables people in different places to discuss and make decisions on connected computers. Expanding GSS capabilities from the knowledge management perspective is believed to significantly improve the performance and satisfaction of group meetings. This study develops the organizational knowledge management process, proposed by Alavi and Leidner (2001), to expand the capabilities of a GSS. Additionally, a prototype system has been implemented. Finally, an experiment is conducted to evaluate the system and demonstrate its applicability and usability. Experimental results indicate that users perceive a web-based GSS with knowledge management capabilities to be more helpful and more satisfying than a conventional GSS. They also perceived that using a web-based GSS with knowledge management capabilities can improve the decision quality

ROLE OF ANNEXIN-1 IN PATHOGEN RECOGNITION AND IMMUNE RESPONSE

Ph.DDOCTOR OF PHILOSOPH

Primordial perturbations from ultra-slow-roll single-field inflation with quantum loop effects

It is known that the single-field inflation with a transient ultra-slow-roll phase can produce a large curvature perturbation at small scales for the formation of primordial black holes. In our previous work, we have considered quantum loop corrections to the curvature perturbation and found that the growth of these small-scale modes would affect the curvature perturbation at large scales probed by cosmic microwave background observation. In this work, we will further derive the constraints on the growing modes in the transition between the slow-roll and the ultra-slow-roll phases under the effect of the loop corrections. Our results would help clarify the recent controversy on whether or not the primordial-black-hole formation from the single-field inflation is ruled out at one-loop level.Comment: 24 pages, 14 figure

High-definition vertically aligned liquid crystal microdisplays using a circularly polarized light

A high-definition vertically aligned liquid crystal (LC) microdisplay exhibits a excellent contrast ratio, but its fringing field effect splits the bright state unevenly and leads to a very slow response time. By utilizing a circularly polarized light instead of conventional linearly polarized light, we have overcome the long-standing problems of poor sharpness, low brightness, and slow response time. Confirming computer simulations agree with the experimental results well. This approach can be applied to both reflective and transmissive LC microdisplays

Chemokine GPCR signaling inhibits beta-catenin during Zebrafish axis formation

Embryonic axis formation in vertebrates is initiated by the establishment of the dorsal Nieuwkoop blastula organizer, marked by the nuclear accumulation of maternal β-catenin, a transcriptional effector of canonical Wnt signaling. Known regulators of axis specification include the canonical Wnt pathway components that positively or negatively affect β-catenin. An involvement of G-protein coupled receptors (GPCRs) was hypothesized from experiments implicating G proteins and intracellular calcium in axis formation, but such GPCRs have not been identified. Mobilization of intracellular Ca(2+) stores generates Ca(2+) transients in the superficial blastomeres of zebrafish blastulae when the nuclear accumulation of maternal β-catenin marks the formation of the Nieuwkoop organizer. Moreover, intracellular Ca(2+) downstream of non-canonical Wnt ligands was proposed to inhibit β-catenin and axis formation, but mechanisms remain unclear. Here we report a novel function of Ccr7 GPCR and its chemokine ligand Ccl19.1, previously implicated in chemotaxis and other responses of dendritic cells in mammals, as negative regulators of β-catenin and axis formation in zebrafish. We show that interference with the maternally and ubiquitously expressed zebrafish Ccr7 or Ccl19.1 expands the blastula organizer and the dorsoanterior tissues at the expense of the ventroposterior ones. Conversely, Ccr7 or Ccl19.1 overexpression limits axis formation. Epistatic analyses demonstrate that Ccr7 acts downstream of Ccl19.1 ligand and upstream of β-catenin transcriptional targets. Moreover, Ccl19/Ccr7 signaling reduces the level and nuclear accumulation of maternal β-catenin and its axis-inducing activity and can also inhibit the Gsk3β -insensitive form of β-catenin. Mutational and pharmacologic experiments reveal that Ccr7 functions during axis formation as a GPCR to inhibit β-catenin, likely by promoting Ca(2+) transients throughout the blastula. Our study delineates a novel negative, Gsk3β-independent control mechanism of β-catenin and implicates Ccr7 as a long-hypothesized GPCR regulating vertebrate axis formation