Mammalian Lgl Forms a Protein Complex with PAR-6 and aPKC Independently of PAR-3 to Regulate Epithelial Cell Polarity

AbstractBackground: Epithelial cells have apicobasal polarity and an asymmetric junctional complex that provides the bases for development and tissue maintenance. In both vertebrates and invertebrates, the evolutionarily conserved protein complex, PAR-6/aPKC/PAR-3, localizes to the subapical region and plays critical roles in the establishment of a junctional complex and cell polarity. In Drosophila, another set of proteins called tumor suppressors, such as Lgl, which localize separately to the basolateral membrane domain but genetically interact with the subapical proteins, also contribute to the establishment of cell polarity. However, how physically separated proteins interact remains to be clarified.Results: We show that mammalian Lgl competes for PAR-3 in forming an independent complex with PAR-6/aPKC. During cell polarization, mLgl initially colocalizes with PAR-6/aPKC at the cell-cell contact region and is phosphorylated by aPKC, followed by segregation from apical PAR-6/aPKC to the basolateral membrane after cells are polarized. Overexpression studies establish that increased amounts of the mLgl/PAR-6/aPKC complex suppress the formation of epithelial junctions; this contrasts with the previous observation that the complex containing PAR-3 promotes it.Conclusions: These results indicate that PAR-6/aPKC selectively interacts with either mLgl or PAR-3 under the control of aPKC activity to regulate epithelial cell polarity

Stability test results on the aluminum stabilized superconductor for the helical coils of LHD

Stability tests have been carried out on short samples of the aluminum/copper stabilized composite-type superconductors developed and used for the pool-cooled helical coils of the Large Helical Device. The waveform of the longitudinal voltage initiated by resistive heaters shows a short-time rise before reaching a final value, which seems to correspond to the diffusion process of transport current into the pure aluminum stabilizer. The propagation velocity has a finite value even for the transport current being lower than the recovery current, and it differs depending on the direction with respect to the transport current

Copper recovery and reduction of environmental loading from mine tailings by high‐pressure leaching and sx‐ew process

The flotation tailings obtained from Bor Copper Mine contain pyrite (FeS2) and chalcopyrite (CuFeS2), these sulfide minerals are known to promote acid mine drainage (AMD) which poses a serious threat to the environment and human health. This study focuses on the treatment of mine tailings to convert the AMD supporting minerals to more stable forms, while simultaneously valorizing the mine tailings. A combination of hydrometallurgical processes of high-pressure oxidative leaching (HPOL), solvent extraction (SX), and electrowinning (EW) were utilized to recover copper from mine tailings which contain about 0.3% Cu content. The HPOL process yielded a high copper leaching rate of 94.4% when water was used as a leaching medium. The copper leaching kinetics were promoted by the generation of sulfuric acid due to pyrite oxidation. It was also confirmed that a low iron concentration (1.4 g/L) and a high copper concentration (44.8 g/L) obtained in the stripped solution resulted in an improved copper electrodeposition current efficiency during copper electrowinning.Moreover, pyrite, which is primarily in the mine tailings, was converted into hematite after HPOL. A stability evaluation of the solid residue confirmed almost no elution of metal ions, confirming the reduced environmental loading of mine tailings through re-processing

R&D Progress of HTS Magnet Project for Ultrahigh-field MRI

Proceedings of the 28th International Symposium on Superconductivity (ISS 2015) November 16-18, 2015, Tokyo, JapanAn R&D project on high-temperature superconducting (HTS) magnets using rare-earth Ba2Cu3O7 (REBCO) wires was started in 2013. The project objective is to investigate the feasibility of adapting REBCO magnets to ultrahigh field (UHF) magnetic resonance imaging (MRI) systems. REBCO wires are promising components for UHF-MRI magnets because of their superior superconducting and mechanical properties, which make them smaller and lighter than conventional ones. Moreover, REBCO magnets can be cooled by the conduction-cooling method, making liquid helium unnecessary. In the past two years, some test coils and model magnets have been fabricated and tested. This year is the final year of the project. The goals of the project are: (1) to generate a 9.4 T magnetic field with a small test coil, (2) to generate a homogeneous magnetic field in a 200 mm diameter spherical volume with a 1.5 T model magnet, and (3) to perform imaging with the 1.5 T model magnet. In this paper, the progress of this R&D is described. The knowledge gained through these R&D results will be reflected in the design of 9.4 T MRI magnets for brain and whole body imaging

Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1G93A mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H2O2-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS

Generation and Characterization of Conditional Heparin-Binding EGF-Like Growth Factor Knockout Mice

Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder