The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.     

自然风力作用下草体运动的模拟方法

实时生成自然风力影响下植物的自然摇曳效果是图形学中的难点问题之一.讨论了一种基于快速纹理合成算法的草体运动模拟方法,利用星形结构透明纹理在风力模型作用下产生的变形,结合星状匹配的纹理合成算法,对自然风力影响下草体的动态效果进行了快速有效的模拟,仿真试验的效果进一步证明了算法的有效性和可行性,结果表明,该方法可适用于游戏制作和虚拟场景构建等领域.     

Effects of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on posterior alpha wave

Because of the unclear conclusion of the repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) effects on the posterior electroencephalogram (EEG) alpha wave, this study is aimed at investigating these unclear effects. Transcranial stimulation effects are observed by analyzing a measured EEG at the occipital area between prestimulation and the poststimulation. The EEG alpha power and alpha coherence are calculated and analyzed in terms of the ratio between eyes closed and eyes open periods. The results reveal that alpha power ratio at the individual alpha frequency (IAF) significantly increases after the 1‐Hz rTMS and cathodal tDCS and slightly decreases after the anodal tDCS compared to the control and the sham conditions. The results also show that there is a significant difference between the inhibited and excited conditions. Similarities are observed in the patterns of the alpha coherence ratio and alpha power changes. The alpha coherence increases in the rTMS and cathodal tDCS conditions, and decreases in the anodal tDCS condition but these effects occur only when comparing across the hemispheres (O1–O2 and P3–P4). It can be summarized that the EEG alpha wave can be influenced by the transcranial stimulations. The rTMS and cathodal tDCS seem to facilitate the alpha activity and the anodal tDCS inhibits it. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.     

The influence of low- and high-linear energy transfers on some physical properties of poly(methyl-methacrylate) samples

Clear poly(methyl-methacrylate)—PMMA—dosimeter is widely used in food irradiations. Positron annihilation lifetime spectroscopy (PALS) is one of the unique tools used for studying free-volumes and open-volume type defects in solid media. The Vicker's microhardness measurements offer a simple and nondestructive tool for investigating the mechanical behavior of polymer materials. PALS as well as microhardness measurements were carried out for PMMA samples, irradiated with low- and high-linear energy transfers (LET). The low-LET irradiations were provided at lethal doses of gamma radiations for vegetative bacteria. Such irradiations showed a chain scission in the PMMA samples. High-LET irradiations showed behavior different from the low-LET ones. The observed behavior depends on the alpha particle fluence. The microhardness testing was carried out for virgin and irradiated PMMA samples at high-LET. A negative correlation was found between PALS measurements and microhardness results. The optical characteristics and structural studies for the virgin and irradiated PMMA samples were in agreement with the PALS and microhardness measurements. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Radioactivity Measurements on Glazed Ceramic Surfaces

A variety of commonly available household and industrial ceramic items and some specialty glass materials were assayed by alpha pulse counting and ion chamber voltage measurements for radioactivity concentrations. Identification of radionuclides in some of the items was performed by gamma spectroscopy. The samples included tableware, construction tiles and decorative tiles, figurines, and other products with a clay based composition. The concentrations of radioactivity ranged from near background to about four orders of magnitude higher. Almost every nuclide identification test demonstrated some radioactivity content from one or more of the naturally occurring radionuclide series of thorium or uranium. The glazes seemed to contribute most of the activity, although a sample of unglazed pottery greenware showed some activity. Samples of glazing paints and samples of deliberately doped glass from the World War II era were included in the test, as was a section of foam filled poster board. A glass disc with known ²³²Th radioactivity concentration was cast for use as a calibration source. The results from the two assay methods are compared, and a projection of sensitivity from larger electret ion chamber devices is presented.     

A Study on Melody Tempo with EEG

In this paper, tempo perception is investi- gated by recording spontaneous electroencephalograph （EEG）. Ten normal male non-musician college students are selected according to questionnaire results after listening absorbedly to four different tempos of an excerpt from a Mozart sonata. EEGs data are recorded when the subjects are listening to the music. The EEG spectral power （SP） is analyzed for alpha band. The varying trend of power spectrum during exposure to music excerpts of different tempos is studied and shows the consistence with the previous tempo-specific hypothesis： a tempo-transformed performance will sound less natural than an original performance does. The results presented in this paper suggest that tempo is an important factor that could influence the alpha rhythm.     

Tail pinching-induced hindlimb movements are suppressed by clonidine in spinal cord injured mice.

Experiments in completely spinal cord transected (Tx) cats have provided compelling evidence that clonidine combined with tail stimulation can promote locomotor function recovery. However, clonidine has generally failed to induce locomotor activity in other comparable animal models suggesting the existence of species- or condition-specific effects. This study aimed at investigating the effects of clonidine administered (0.25 or 5.0 mg/kg, i.p.) in mice during tail pinching in early (6-7 days post-Tx) or late (41-42 days post-Tx) paraplegic animals (Th9/10 level). Comparisons were made with the effects induced by 8-OH-DPAT (1.0 mg/kg, i.p.), a 5-HT1A/7 receptor agonist known to display prolocomotor effects. Clonidine with or without tail pinching failed to induce hind limb movements and even suppressed the frequency of spontaneously occurring nonlocomotor (NLM) and locomotor-like movements (LM) whereas tail pinching alone (prior to clonidine administration) increased the frequency of spontaneous movements specifically in late chronic animals. In turn, 8-OH-DPAT clearly induced hind limb movements that remained relatively unchanged during tail pinching. Altogether, the results suggest that the prolocomotor effects of clonidine reported elsewhere must depend upon stimuli or factors that remain to be identified. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pathogenic Mutations Shift the Equilibria of α‐Synuclein Single Molecules towards Structured Conformers

α‐synuclein (α‐Syn) is an abundant brain protein whose mutations have been linked to early‐onset Parkinson's disease (PD). We recently demonstrated, by means of a single‐molecule force spectroscopy (SMFS) methodology, that the conformational equilibrium of monomeric wild‐type (WT) α‐Syn shifts toward β‐containing structures in several unrelated conditions linked to PD pathogenicity. Herein, we follow the same methodology previously employed for WT α‐Syn to characterize the conformational heterogeneity of pathological α‐Syn mutants A30P, A53T, and E46K. Contrary to the bulk ensemble‐averaged spectroscopies so far employed to this end by different authors, our single‐molecule methodology monitored marked differences in the conformational behaviors of the mutants with respect to the WT sequence. We found that all the mutants have a much higher propensity than the WT to adopt a monomeric compact conformation that is compatible with the acquiring of β structure. Mutants A30P and A53T show a similar conformational equilibrium that is significantly different from that of E46K. Another class of conformations, stabilized by mechanically weak interactions (MWI), shows a higher variety in the mutants than in the WT protein. In the A30P mutant these interactions are relatively stronger, and therefore the corresponding conformations are possibly more structured. The more structured and globular conformations of the mutants can explain their higher propensity to aggregate with respect to the WT.     

Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia

Phosphoinositides (PIs) play important roles in the structure and function of the brain. Associations between PIs and the pathophysiology of schizophrenia have been studied. However, the significance of the PI metabolic pathway in the pathology of schizophrenia is unknown. We examined the expression of PI signaling-associated proteins in the postmortem brain of schizophrenia patients. Protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA, also known as PIK4A), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), protein kinase B (Akt), and glycogen synthase kinase 3β (GSK3β) were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays of the prefrontal cortex (PFC) of postmortem samples from 23 schizophrenia patients and 47 normal controls. We also examined the association between PIK4CA expression and its genetic variants in the same brain samples. PIK4CA expression was lower, whereas Akt expression was higher, in the PFC of schizophrenia patients than in that of controls; PIP5K1C, PTEN, and GSK3β expression was not different. No single-nucleotide polymorphism significantly affected protein expression. We identified molecules involved in the pathology of schizophrenia via this lipid metabolic pathway. These results suggest that PIK4CA is involved in the mechanism underlying the pathogenesis of schizophrenia and is a potential novel therapeutic target.