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

To the Edge of M87 and Beyond: Spectroscopy of Intracluster Globular Clusters and Ultra Compact Dwarfs in the Virgo Cluster

We present the results from a wide-field spectroscopic survey of globular clusters (GCs) in the Virgo Cluster. We obtain spectra for 201 GCs and 55 ultracompact dwarfs (UCDs) using the Hectospec on the Multiple Mirror Telescope, and derive their radial velocities. We identify 46 genuine intracluster GCs (IGCs), not associated with any Virgo galaxies, using the 3D GMM test on the spatial and radial velocity distribution.They are located at the projected distance 200 kpc $\lesssim$ R $\lesssim$ 500 kpc from the center of M87. The radial velocity distribution of these IGCs shows two peaks, one at $v_{\rm r}$ = 1023 km s$^{-1}$ associated with the Virgo main body, and another at $v_{\rm r}$ = 36 km s$^{-1}$ associated with the infalling structure. The velocity dispersion of the IGCs in the Virgo main body is $\sigma_{\rm{GC}} \sim$ 314 km s$^{-1}$, which is smoothly connected to the velocity dispersion profile of M87 GCs, but much lower than that of dwarf galaxies in the same survey field, $\sigma_{\rm{dwarf}} \sim$ 608 km s$^{-1}$. The UCDs are more centrally concentrated on massive galaxies, M87, M86, and M84. The radial velocity dispersion of the UCD system is much smaller than that of dwarf galaxies. Our results confirm the large-scale distribution of Virgo IGCs indicated by previous photometric surveys. The color distribution of the confirmed IGCs shows a bimodality similar to that of M87 GCs. This indicates that most IGCs are stripped off from dwarf galaxies and some from massive galaxies in the Virgo.Comment: 19 pages, 20 figures, 8 tables, accepted for publication in Ap

Role of G{alpha}12 and G{alpha}13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

G{alpha}12 and G{alpha}13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by G{alpha}12 and G{alpha}13. A deficiency of G{alpha}12, but not of G{alpha}13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, G{alpha}12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by G{alpha}12 gene knockout. G{alpha}12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did G{alpha}13 deficiency. The absence of G{alpha}12, but not of G{alpha}13, increased protein kinase C {delta} (PKC {delta}) activation and the PKC {delta}-mediated serine phosphorylation of Nrf2. G{alpha}13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by G{alpha}12 deficiency, suggesting that relief from G{alpha}12 repression leads to the G{alpha}13-mediated activation of Nrf2. Constitutive activation of G{alpha}13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC {delta} activation, corroborating positive regulation by G{alpha}13. In summary, G{alpha}12 and G{alpha}13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas G{alpha}13 regulates Rho-PKC {delta}-mediated Nrf2 phosphorylation, which is negatively balanced by G{alpha}12

Splenectomy is associated with an aggressive tumor growth pattern and altered host immunity in an orthotopic syngeneic murine pancreatic cancer model.

The purpose of this study was to investigate whether splenectomy influences the tumor growth and metastatic pattern in an orthotopic syngeneic murine pancreatic cancer model. Murine pancreatic cancer cells (PAN02) were subcutaneously injected into the flanks of nude mice. A small tumor fragment (3 mm2), harvested from a subcutaneous tumor. was orthotopically implanted in the tail of the pancreas of C57/BL6 mice without splenectomy (control group, n=15) or with simultaneous splenectomy (splenectomy group, n=15). Tumor growth and metastatic patterns were analyzed by laparotomy at 21 days after surgery. No tumor growth was found in 5 mice (33.3%) of the control group and 1 mouse (6.7%) of the splenectomy group (p=0.169). Tumor volume was significantly larger in splenectomy group (p=0.013). Peritoneal seeding was more frequently observed in the splenectomy group (11 (73.3%) vs. 4 (26.7%), p=0.011). There were no differences in the number of liver and kidney metastasis between the two groups. The ratios of tumor-infiltrating CD4+ to FoxP3+ and CD8+ to FoxP3+ were significantly higher in the control group compared to the splenectomy group (8.2 ± 9.3 vs. 2.4 ± 1.5, p=0.046; 2.5 ± 1.4 vs. 1.5 ± 0.4, p=0.031, respectively). Splenectomy enhanced tumor growth and peritoneal seeding in an orthotopic syngeneic murine pancreatic cancer mouse model. The ramification of these results are discussed for pancreatic cancer treatment

Increasing the Durability of Piezoelectric Impact-based Micro Wind Generator in Real Application

AbstractThe purpose of this study is to increase the durability of piezoelectric impact-based micro wind generator (PIMWG) in real application. Using new PIMWG design, numerical simulation, and experimental comparison analysis, we improved the durability of PIMWGs in real application. The experimental results show that the optimized PIMWG generated 2.4 mW (RMS value), and it did not crack within 40h. In this study, we improved the durability of PIMWGs for real application

Formation characteristics and photoluminescence of Ge nanocrystals in HfO[sub 2]

Genanocrystals (NCs) are shown to form within HfO₂ at relatively low annealing temperatures (600–700 °C) and to exhibit characteristic photoluminescence(PL) emission consistent with quantum confinement effects. After annealing at 600 °C, sample implanted with 8.4×10¹⁵ Ge cm⁻² show two major PL peaks, at 0.94 and 0.88 eV, which are attributed to no-phonon and transverse-optical phonon replica of Ge NCs, respectively. The intensity reaches a maximum for annealing temperatures around 700 °C and decreases at higher temperatures as the NC size continues to increase. The no-phonon emission also undergoes a significant redshift for temperatures above 800 °C. For fluences in the range from 8.4×1015 to 2.5×10¹⁶ cm⁻², the average NC size increases from ∼13.5±2.6 to ∼20.0±3.7 nm. These NC sizes are much larger than within amorphous SiO₂. Implanted Ge is shown to form Ge NCs within the matrix of monoclinic (m)-HfO₂ during thermal annealing with the orientation relationship of [101]m-HfO₂//[110]Ge NC.S.H.C. and R.G.E. acknowledge supports from the Korea Research Foundation Grant Grant No. KRF-2007-521- C00094 and from the Australian Research Council Discovery Project, respectively

Manufacturing method of photonic crystal

A manufacturing method of a photonic crystal is provided. In the method, a high-refractive-index material is conformally deposited on an exposed portion of a periodic template composed of a low-refractive-index material by an atomic layer deposition process so that a difference in refractive indices or dielectric constants between the template and adjacent air becomes greater, which makes it possible to form a three-dimensional photonic crystal having a superior photonic bandgap. Herein, the three-dimensional structure may be prepared by a layer-by-layer method

Sex- and Age-Related Changes in Connexin 43 Expression in Normal Rat Bladder

Purpose Gap junctions are intercellular channels to facilitate electrical and metabolic communication between adjacent cells. Connexin 43 is the most predominant type of connexin expressed on rat detrusor muscle cells. We investigated the connexin 43 expressions in various age groups of either sex in normal rats. Methods Eighty Sprague-Dawley rats were used for analysis. Each group was quantified by 8 rats at 1 week, 2 weeks, 1 month, 3 months, and 6 months of age in either sex. In each animal, bladder was removed without any kind of intervention and fresh-frozen in liquid nitrogen. Total RNA extraction was done with easy-BLUE total RNA extraction kit. Reverse transcription polymerase chain reaction was done for connexin 43 and glyceraldehyde-3-phosphate dehydrogenase as an internal control using ImProm-II Reverse Transcription System. Results In female rats, no age-related change was detected in connexin 43 expressions. In male rats, connexin expression at 3 months of age showed significant decrease compared with 1 week, 2 weeks, and 6 months of age (P<0.05). When connexin expression at the same age in male and female were compared, only 3 months group in male showed significant decrease than the same age group in female. Conclusions Our data suggest that the expressions of connexin 43 mRNA in normal detrusor muscle cell showed age-related changes especially in male rats. Although it is difficult to interpret these findings at this stage, age should be considered as a possible compounding factor affecting connexin 43 expressions in male rats

Plasmonic Terahertz Wave Detector Based on Silicon Field-Effect Transistors with Asymmetric Source and Drain Structures

In this paper, we present the validity and potential capacity of a modeling and simulation environment for the nonresonant plasmonic terahertz (THz) detector based on the silicon (Si) field-effect transistor (FET) with a technology computer-aided design (TCAD) platform. The nonresonant and &quot;overdamped&quot; plasma-wave behaviors have been modeled by introducing a quasi-plasma electron charge box as a two-dimensional electron gas (2DEG) in the channel region only around the source side of Si FETs. Based on the coupled nonresonant plasma-wave physics and continuity equation on the TCAD platform, the alternate-current (AC) signal as an incoming THz wave radiation successfully induced a direct-current (DC) drain-to-source output voltage as a detection signal in a sub-THz frequency regime under the asymmetric boundary conditions with a external capacitance between the gate and drain. The average propagation length and density of a quasi-plasma have been confirmed as around 100 nm and 1x10(19)/cm(3), respectively, through the transient simulation of Si FETs with the modulated 2DEG at 0.7 THz. We investigated the incoming radiation frequency dependencies on the characteristics of the plasmonic THz detector operating in sub-THz nonresonant regime by using the quasi-plasma modeling on TCAD platform. The simulated dependences of the photoresponse with quasi-plasma 2DEG modeling on the structural parameters such as gate length and dielectric thickness confirmed the operation principle of the nonresonant plasmonic THz detector in the Si PET structure. The proposed methodologies provide the physical design platform for developing novel plasmonic THz detectors operating in the nonresonant detection mode.open3