Genome-wide analysis to predict protein sequence variations that change phosphorylation sites or their corresponding kinases

We define phosphovariants as genetic variations that change phosphorylation sites or their interacting kinases. Considering the essential role of phosphorylation in protein functions, it is highly likely that phosphovariants change protein functions and may constitute a proportion of the mechanisms by which genetic variations cause individual differences or diseases. We categorized phosphovariants into three subtypes and developed a system that predicts them. Our method can be used to screen important polymorphisms and help to identify the mechanisms of genetic diseases

Analysis of Slab and Slab Heater Cover in a Compact Endless Cast and Rolling Mill Process using Finite Element Methods

Compact Endless cast and rolling Mill (CEM) processes were developed and used to fabricate steel products such as steel slabs. However, the coiling furnace in this process was very expensive, so a new layout was suggested. As the coiling furnace was removed, the interval among the slab heaters had to be increased. This led to a temperature drop in the slab. The temperature distribution of the slab impacts quality, so new layout was developed. This paper presents a Finite Element Method (FEM) simulation of thermal behavior in the slab employing slab heater covers. All of the simulation results were verified by comparing them with experimental results. The slab moving distance at which the temperature was saturated during the process was determined to consider the steady-state and analyze the temperature distribution of the slab and slab heater. Those results revealed that the efficiency of heat conservation increased by more than 50% using the slab heater cover. Finally, a sensitivity analysis of the slab heater cover was conducted with respect to the cover design. The effects of insulator thickness, the gap distance between the slab and cover, and material parameters such as density, and specific heat were investigated to optimize the design of the slab heater cover to produce the best quality slab.11Ysciescopuskc

Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis

Synaptic transmission between midbrain dopamine neurons and target neurons in the striatum is essential for the selection and reinforcement of movements. Recent evidence indicates that nigrostriatal dopamine neurons inhibit striatal projection neurons by releasing a neurotransmitter that activates GABAA receptors. Here, we demonstrate that this phenomenon extends to mesolimbic afferents, and confirm that the released neurotransmitter is GABA. However, the GABA synthetic enzymes GAD65 and GAD67 are not detected in midbrain dopamine neurons. Instead, these cells express the membrane GABA transporters mGAT1 (Slc6a1) and mGAT4 (Slc6a11) and inhibition of these transporters prevents GABA co-release. These findings therefore indicate that GABA co-release is a general feature of midbrain dopaminergic neurons that relies on GABA uptake from the extracellular milieu as opposed to de novo synthesis. This atypical mechanism may confer dopaminergic neurons the flexibility to differentially control GABAergic transmission in a target-dependent manner across their extensive axonal arbors. DOI: http://dx.doi.org/10.7554/eLife.01936.00

PAGaN I: Multi-Frequency Polarimetry of AGN Jets with KVN

Active Galactic Nuclei (AGN) with bright radio jets offer the opportunity to study the structure of and physical conditions in relativistic outflows. For such studies, multi-frequency polarimetric very long baseline interferometric (VLBI) observations are important as they directly probe particle densities, magnetic field geometries, and several other parameters. We present results from first-epoch data obtained by the Korean VLBI Network (KVN) within the frame of the Plasma Physics of Active Galactic Nuclei (PAGaN) project. We observed seven radio-bright nearby AGN at frequencies of 22, 43, 86, and 129 GHz in dual polarization mode. Our observations constrain apparent brightness temperatures of jet components and radio cores in our sample to $>10^{8.01}$ K and $>10^{9.86}$ K, respectively. Degrees of linear polarization $m_{L}$ are relatively low overall: less than 10%. This indicates suppression of polarization by strong turbulence in the jets. We found an exceptionally high degree of polarization in a jet component of BL Lac at 43 GHz, with $m_{L} \sim$ 40%. Assuming a transverse shock front propagating downstream along the jet, the shock front being almost parallel to the line of sight can explain the high degree of polarization.Comment: 14 pages, 17 figures, 4 tables. To appear in JKAS (received 2015 July 27; accepted 2015 October 25). Note the PAGaN II companion paper by J. Oh et a

Cleft Palate Is Caused by CNS Dysfunction in Gad1 and Viaat Knockout Mice

BACKGROUND: Previous studies have shown that disruption of GABA signaling in mice via mutations in the Gad1, Gabrb3 or Viaat genes leads to the development of non-neural developmental defects such as cleft palate. Studies of the Gabrb3 and Gad1 mutant mice have suggested that GABA function could be required either in the central nervous system or in the palate itself for normal palatogenesis. METHODOLOGY/PRINCIPAL FINDINGS: To further examine the role of GABA signaling in palatogenesis we used three independent experimental approaches to test whether Gad1 or Viaat function is required in the fetal CNS for normal palate development. We used oral explant cultures to demonstrate that the Gad1 and Viaat mutant palates were able to undergo palatogenesis in culture, suggesting that there is no defect in the palate tissue itself in these mice. In a second series of experiments we found that the GABA(A) receptor agonist muscimol could rescue the cleft palate phenotype in Gad1 and Viaat mutant embryos. This suggested that normal multimeric GABA(A) receptors in the CNS were necessary for normal palatogenesis. In addition, we showed that CNS-specific inactivation of Gad1 was sufficient to disrupt palate development. CONCLUSIONS/SIGNIFICANCE: Our results are consistent with a role for Gad1 and Viaat in the central nervous system for normal development of the palate. We suggest that the alterations in GABA signaling lead to non-neural defects such as cleft palate as a secondary effect due to alterations in or elimination of fetal movements

Effects on Growth and Osteogenic Differentiation of Mesenchymal Stem Cells by the Zinc-Added Sol-Gel Bioactive Glass Granules

Responses of mesenchymal stem cells (MSCs) cultured with zinc-added (2 and 5%) bioactive glass granules were evaluated in terms of cell growth and osteogenic differentiation. MSCs were cultured with different quantities (3, 10 and 30) of glass granules for up to 21 days in the osteogenic medium. Cell growth was stimulated by a small quantity of glasses, particularly those that contained zinc. Osteogenic differentiation, as assessed by alkaline phosphatase activity (ALP) activity, was significantly enhanced by the glasses, particularly with large quantities of glass and for prolonged culturing. Expression of bone-sialo protein (BSP) was significantly up-regulated around the bioactive glass granules. Moreover, the zinc addition significantly altered the ALP and BSP depending on the culture time and glass quantity. Cellular mineralization was improved in all glass samples, and particularly in the 2% zinc-glass. Taken together, the zinc addition to bioactive glass induced the MSCs growth and their osteogenic differentiation, at least to the level of zinc-free glass, and with even higher level observed depending on the quantity and culture time. These findings indicate that the zinc addition to bioactive glass may be useful in development of biomaterials for the stimulation of adult stem cell in bone tissue engineering

Preparation, characterization and photocatalytic behavior of WO3-fullerene/TiO2 catalysts under visible light

WO3-treated fullerene/TiO2 composites (WO3-fullerene/TiO2) were prepared using a sol-gel method. The composite obtained was characterized by BET surface area measurements, X-ray diffraction, scanning electron microscopy, energy dispersive X-ray analysis, transmission electron microscopy, and UV-vis analysis. A methyl orange (MO) solution under visible light irradiation was used to determine the photocatalytic activity. Excellent photocatalytic degradation of a MO solution was observed using the WO3-fullerene, fullerene-TiO2, and WO3-fullerene/TiO2 composites under visible light. An increase in photocatalytic activity was observed, and WO3-fullerene/TiO2 has the best photocatalytic activity; it may attribute to the increase of the photo-absorption effect by the fullerene and the cooperative effect of the WO3

PAGaN II: The Evolution of AGN Jets on Sub-Parsec Scales

We report first results from KVN and VERA Array (KaVA) VLBI observations obtained in the frame of our Plasma-physics of Active Galactic Nuclei (PAGaN) project. We observed eight selected AGN at 22 and 43 GHz in single polarization (LCP) between March 2014 and April 2015. Each source was observed for 6 to 8 hours per observing run to maximize the $uv$ coverage. We obtained a total of 15 deep high-resolution images permitting the identification of individual circular Gaussian jet components and three spectral index maps of BL Lac, 3C 111 and 3C 345 from simultaneous dual-frequency observations. The spectral index maps show trends in agreement with general expectations -- flat core and steep jets -- while the actual value of the spectral index for jets shows indications for a dependence on AGN type. We analyzed the kinematics of jet components of BL Lac and 3C 111, detecting superluminal proper motions with maximum apparent speeds of about $5c$. This constrains the lower limits of the intrinsic component velocities to $\sim0.98c$ and the upper limits of the angle between jet and line of sight to $\sim$20$\deg$. In agreement with global jet expansion, jet components show systematically larger diameters $d$ at larger core distances $r$, following the global relation $d\approx0.2r$, albeit within substantial scatter.Comment: 13 pages, 15 figures, 4 tables. To appear in JKAS (received 2015 August 31; accepted 2015 October 15). Note the PAGaN I companion paper by J.-Y. Kim et a