Phenomenological Implications of the Topflavor Model

We explore phenomenologies of the topflavour model for the LEP experiment at $m_{_Z}$ scale and the atomic parity violation (APV) experiment in the $C_s$ atoms at low energies. Implications of the model on the $Z$ peak data are studied in terms of the precision variables $\epsilon_i$'s. We find that the LEP data give more stringent constraints on the model parameters than the APV data.Comment: 23 pages (including 5 .eps figs), ReVTeX, the 1st revised version, to appear in Phys. Lett.

The Interaction of Phospholipase C-{beta}3 with Shank2 Regulates mGluR-mediated Calcium Signal

Phospholipase C-{beta} isozymes that are activated by G protein-coupled receptors (GPCR) and heterotrimeric G proteins carry a PSD-95/Dlg/ZO-1 (PDZ) domain binding motif at their C terminus. Through interactions with PDZ domains, this motif may endow the PLC-{beta} isozyme with specific roles in GPCR signaling events that occur in compartmentalized regions of the plasma membrane. In this study, we identified the interaction of PLC-{beta}3 with Shank2, a PDZ domain-containing multimodular scaffold in the postsynaptic density (PSD). The C terminus of PLC-{beta}3, but not other PLC-{beta} isotypes, specifically interacts with the PDZ domain of Shank2. Homer 1b, a Shank-interacting protein that is linked to group I metabotropic glutamate receptors and IP3 receptors, forms a multiple complex with Shank2 and PLC-{beta}3. Importantly, microinjection of a synthetic peptide specifically mimicking the C terminus of PLC-{beta}3 markedly reduces the mGluR-mediated intracellular calcium response. These results demonstrate that Shank2 brings PLC-{beta}3 closer to Homer 1b and constitutes an efficient mGluR-coupled signaling pathway in the PSD region of neuronal synapses

Agmatine modulates the phenotype of macrophage acute phase after spinal cord injury in rats

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/ kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206+ & ED1+ cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype. © Experimental Neurobiology 201