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

Synthesis of Eu-doped (Gd,Y) 2 O 3 transparent optical ceramic scintillator

A novel process for transparent oxide ceramic scintillator with a composition of Gd 1.94-x Y x Eu 0.06 O 3 was developed. The process consists of a glycine-nitrate combustion synthesis of nano-sized starting powder and subsequent controlled sintering and annealing steps. The organic molecules remaining in the as-combusted powder were efficiently removed by the combined heat-treatment at vacuum and air atmospheres. Hot-pressed ceramic scintillators show transparent optical state and high light output. Transparent optical ceramic scintillator with a high content of Gd (up to 80 mol%) was fabricated by the process. The measured light output of Gd 1.54 Y 0.4 Eu 0.06 O 3 ceramic scintillator was about two times higher that that of CdWO 4 single crystal. In a typical radiation detection system, the scintillator plays the key role of converting the incident energy of ionizing radiation into scintillation light photons, then the emitted lights are collected by the under-laid photosensor. This specific application requires an ideal scintillator that has high light output, fast decay property, low afterglow, and so forth. Recently, a large number of new scintillator systems has been reviewed, 1 resulting, in part, with the development of a new class of scintillator: the polycrystalline ceramic scintillator

Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin

Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The beta-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus

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

Optical switching of the Dirac point in graphene multilayer field-effect transistors functionalized with spiropyran

A facile method for achieving optical switching of the Dirac point and conductance in reduced graphene oxide multilayer FETs that are non-covalently functionalized with a photoresponsive spiropyran derivative is presented. The photoresponsive transition from spiropyran to merocyanine induces the reversible optical switching in graphene based FETs.close6

Staphylococcal enterotoxin sensitization in a community-based population : a potential role in adult-onset asthma

Background: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. Objective: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. Methods: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age=60.2years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. Results: Staphylococcal enterotoxin sensitization (0.35kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (61years), and inhalant allergen sensitization. Current asthma was mostly adult onset (18years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. Conclusions and Clinical Relevance: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis

Dependence of GCRs influx on the Solar North-South Asymmetry

We investigate the dependence of the amount of the observed galactic cosmic ray (GCR) influx on the solar North-South asymmetry using the neutron count rates obtained from four stations and sunspot data in archives spanning six solar cycles from 1953 to 2008. We find that the observed GCR influxes at Moscow, Kiel, Climax and Huancayo stations are more suppressed when the solar activity in the southern hemisphere is dominant compared with when the solar activity in the northern hemisphere is dominant. Its reduction rates at four stations are all larger than those of the suppression due to other factors including the solar polarity effect on the GCR influx. We perform the student's t-test to see how significant these suppressions are. It is found that suppressions due to the solar North-South asymmetry as well as the solar polarity are significant and yet the suppressions associated with the former are larger and more significant.Comment: 17 pages, 3figures, accepted to JAST