Mechanisms of GOLPH3 Associated with the Progression of Gastric Cancer: A Preliminary Study

Study Design

To investigate the specific mechanisms by which Golgi phosphoprotein 3 (GOLPH3) affects the progression of gastric cancer and to explore its clinical significance.

Methods

Immunohistochemical analysis was used to evaluate the correlations between GOLPH3, phosphorylated mTOR (p-mTOR), phosphorylated Akt (p-Akt), phosphorylated p70S6 (p-p70S6), phosphorylated 4E-BP1 (p-4E-BP1) and the clinicopathological features of gastric cancer. The mRNA expression levels of GOLPH3, mTOR, Akt, p70S6 and 4E-BP1 in gastric cancer, carcinoma-adjacent and paired normal tissue were analyzed using RT-PCR. Western blotting was used to determine the protein expression of GOLPH3, p-mTOR, p-Akt, p-p70S6 and p-4E-BP1 in tissues.

Results

High expression protein levels of GOLPH3, p-AKT, p-mTOR, p70S6, p-4E-BP1 were positively associated with histological grade (p<0.05), depth of invasion (p<0.05), distant metastasis (p<0.05) and lymph node involvement (p<0.05). Compared with carcinoma-adjacent and paired normal tissues, the mRNA expression levels of GOLPH3, AKT, mTOR, p70S6 and 4EBP1 in gastric cancer tissues were significantly higher. The protein expression levels of GOLPH3, p-AKT, p-mTOR, p-p70S6 and p-4E-BP1 in gastric cancer tissues were also significantly higher than in carcinoma-adjacent and paired normal tissues. A strong positive correlation was observed between GOLPH3, p-mTOR, p-p70S6 and p-4EBP1 expression (r = 0.410, 0.303 and 0.276, respectively, p<0.05), but no significant correlation between the expression of GOLPH3 and p-Akt was observed.

Conclusions

The GOPLH3 expression level is highly correlated with Akt/mTOR signaling in human gastric cancer samples. GOLPH3 combined with Akt/mTOR signaling activation may play an important role in the development, differentiation, invasion and metastasis of gastric cancer.     

Differential Expression of Proteins in Red Pear Following Fruit Bagging Treatment

Fruit bagging is a very effective method for study of fruit qualities and anthocyanin synthesis. The characterization of differentially expressed proteins that were isolated from both bagged and normal fruit skin tissue is apparently an essential parameter for understanding the effect of shading on fruit qualities and to understand the mechanism of fruit coloring in Pyrus communis. Proteome maps of both bagged and normal P. communis 'Placer' fruit skin were obtained by performing two-dimensional electrophoresis analysis and compared to assess the extent to which protein distribution differed in pear skin. The comparative analysis showed 38 differentially expressed proteins between the two samples: with three protein spots up-regulated and 35 down-regulated in the bagged fruit. Differentially expressed protein spots were subjected to matrix-assisted laser desorption ionization time of flight (MALDI-TOF) analysis and the data compared to that of known proteins to deduce their possible functions. Of these, 21 protein spots were identified and classified into functional classes. These identified proteins were mainly involved in photosynthesis, signal transduction, energy pathway, protein folding and assembly, and carbohydrate and acidity metabolisms, and were under-expressed in bagged fruit skins. This work provides a first characterization of the proteome changes in response to fruit bagging treatment in red pears.     

Canine bone marrow mesenchymal stromal cells with lentiviral mHCN4 gene transfer create cardiac pacemakers

Background aimsThe study objective was to test the ability of canine mesenchymal stromal cells (cMSC) transfected with the mouse hyperpolarization-activated cyclic nucleotide-gated channel 4 (mHCN4) gene to deliver a biologic pacemaker to the canine heart.Methods and ResultscMSC that were transfected by lentiviral vector with the cardiac pacemaker gene mHCN4 expressed high levels of Cs⁺ -sensitive current (26.4 ± 1.8pA/pF at –140 mV; (n = 17) and were activated in the diastolic potential range with a reversal potential of –29.7 ± 2.5 mV (n = 14), confirming that the expressed current was Funny current (I_f)-like. Next, 3 × 10⁶ cMSC transfected with either control plasmid or the mHCN4 gene construct were injected subepicardially into the canine right ventricular wall in situ. During sinus arrest, all control hearts had spontaneous atrioventricular node rhythms [rate = 21 ± 5beats per minute (b.p.m.)]. In the mHCN4 group, six of eight animals developed spontaneous ventricular rhythms of right-sided origin (rate = 45 ± 9b.p.m.; P < 0.01). Moreover, immunohistochemical analysis of the injected regions demonstrated neither apoptosis nor cellular or humoral rejection at 2 weeks.ConclusionsThese results demonstrate that genetically modified cMSC can express functional HCN4 channels in vitro and in vivo and represent a novel delivery system for pacemaker genes into the heart.     

Association of IL-6 polymorphisms with gastric cancer risk: evidences from a meta-analysis

The findings of associations between IL-6 polymorphisms and risk of gastric cancer are controversial. We conducted a meta-analysis of the IL-6 gene to provide evidences for the current understanding of the genetic association with gastric cancer. We searched for relevant studies without language restriction in PubMed, EMBASE and Cochrane Library published up to November 2011. The strengths of the associations between IL-6 polymorphisms and gastric cancer risk were estimated by odds ratios (OR) with 95% confidence interval (95% CI). We identified seven case-control studies involving 1364 gastric cancer cases and 1748 controls for the analysis. Because of limited eligible data, our meta-analysis specifically focused on three SNPs of the IL-6 gene, -174 G/C, -572 G/C and -597 G/A. We found no significant associations of IL-6-174 G/C, -572 G/C and -597 G/A polymorphisms with gastric cancer risk in the overall population (all p>0.05). Subgroup analysis did not show significant associations in Asian population or Caucasian population either (all p>0.05). Begg's test and Egger's test suggested no evidence of publication (all p>0.05). Our findings showed that polymorphisms of IL-6-174 G/C, -572 G/C and -597 G/A are not associated with gastric cancer risk. However, the results should be interpreted with caution due to the limited number of studies available.     

Identification and evaluation of ω-3 fatty acid desaturase genes for hyperfortifying α-linolenic acid in transgenic rice seed

α-Linolenic acid (ALA) deficiency and a skewed of ω6:ω3 fatty acid ratio in the diet are a major explanation for the prevalence of cardiovascular diseases and inflammatory/autoimmune diseases. There is a need to enhance the ALA content and to reduce the ratio of linoleic acid (LA) to ALA. Six ω-3 (Δ-15) fatty acid desaturase (FAD) genes were cloned from rice and soybean. The subcellular localizations of the proteins were identified. The FAD genes were introduced into rice under the control of an endosperm-specific promoter, GluC, or a Ubi-1 promoter to evaluate their potential in increasing the ALA content in seeds. The ALA contents in the seeds of endoplasmic reticulum (ER)-localized GmFAD3-1 and OsFAD3 overexpression lines increased from 0.36 mg g?1 to 8.57 mg g?1 and 10.06 mg g?1, respectively, which was 23.8- and 27.9-fold higher than that of non-transformants. The trait of high ALA content was stably inheritable over three generations. Homologous OsFAD3 is more active than GmFAD3-1 in catalysing LA conversion to ALA in rice seeds. Overexpression of ER-localized GmFAD3-2/3 and chloroplast-localized OsFAD7/8 had less effect on increasing the ALA content in rice seeds. The GluC promoter is advantageous compared with Ubi-1 in this experimental system. The enhanced ALA was preferentially located at the sn-2 position in triacylglycerols. A meal-size portion of high ALA rice would meet >80% of the daily adult ALA requirement. The ALA-rich rice could be expected to ameliorate much of the global dietary ALA deficiency.     

Strength Restoration of Cracked Sandstone and Coal under a Uniaxial Compression Test and Correlated Damage Source Location Based on Acoustic Emissions

Underground rock masses have shown a general trend of natural balance over billions of years of ground movement. Nonetheless, man-made underground constructions disturb this balance and cause rock stability failure. Fractured rock masses are frequently encountered in underground constructions, and this study aims to restore the strength of rock masses that have experienced considerable fracturing under uniaxial compression. Coal and sandstone from a deep-buried coal mine were chosen as experimental subjects; they were crushed by uniaxial compression and then carefully restored by a chemical adhesive called MEYCO 364 with an innovative self-made device. Finally, the restored specimens were crushed once again by uniaxial compression. Axial stress, axial strain, circumferential strain, and volumetric strain data for the entire process were fully captured and are discussed here. An acoustic emission (AE) testing system was adopted to cooperate with the uniaxial compression system to provide better definitions for crack closure thresholds, crack initiation thresholds, crack damage thresholds, and three-dimensional damage source locations in intact and restored specimens. Several remarkable findings were obtained. The restoration effects of coal are considerably better than those of sandstone because the strength recovery coefficient of the former is 1.20, whereas that of the latter is 0.33, which indicates that MEYCO 364 is particularly valid for fractured rocks whose initial intact peak stress is less than that of MEYCO 364. Secondary cracked traces of restored sandstone almost follow the cracked traces of the initial intact sandstone, and the final failure is mainly caused by decoupling between the adhesive and the rock mass. However, cracked traces of restored coal only partially follow the traces of intact coal, with the final failure of the restored coal being caused by both bonding interface decoupling and self-breakage in coal. Three-dimensional damage source locations manifest such that AE events are highly correlated with a strength recovery coefficient; the AE events show a decreasing tendency when the coefficient is larger than 1, and vice versa. This study provides a feasible scheme for the reinforcement of fractured rock masses in underground constructions and reveals an internal mechanism of the crushing process for restored rock masses, which has certain instructive significance.     

Hemiboea purpurea sp. nov. (Gesneriaceae) from a limestone area in Guangxi,China

Hemiboea purpurea Yan Liu & W. B. Xu, a new species of Gesneriaceae from Guangxi, China, is described and illustrated. The new species is similar to H. follicularis C. B. Clarke, but differs by smaller leaf blades, 3–10×2–5 cm, corolla purple, ca 2.0–2.5 cm long, exserted from the involucre, filaments glandular‐puberulent and staminodes 3. It is only known from one site in the Rongshui County.     

獐牙菜属植物花蜜腺形态及解剖学

在扫描电镜下观察了獐牙菜属Swertia L.10组30种植物花蜜腺的数目,位置,形态和附属物等特征;同时还利用光镜对各组代表种的蜜腺结构进行了解剖学观察。结果表明獐牙菜属花蜜腺外部形态多种多,但在组与组之间无明显间断,演化序列呈梯度变化;内部结构基本相同,为不具维管束的结构蜜腺,且均为淀粉型蜜腺。因此,从花蜜腺的角度不支持将獐牙菜属划分为小属的观点,同时,还结合其它证据讨论了花蜜腺特征的演化趋势。     

Whole-exome sequencing identifies two novel missense mutations (p.L111P and p.R3048C) of RYR3 in a Vietnamese patient with autism spectrum disorders

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by ritualistic-repetitive behaviors and impaired verbal and non-verbal communication. Boys are more likely to be diagnosed with ASD than girls. Genetics have been shown to play a key role in the etiology of autism. Many genes were found to be implicated in the inheritance of idiopathic autism. Analysis of mutation abnormalities associated with autism contributes significantly to the identification of autism candidate genes. Whole-exome sequencing has been shown as an application of the next generation sequencing technology used to determine the variations of all coding regions, or exons of the known genes. In the present study, we have found two novel heterozygous missense mutations (p.L111P and p.R3048C) on the RYR3 gene, which was located in the autism susceptibility region (15q14-q15) in a 9-year-old boy with ASD. Therefore, the sequence missense mutations provide the first suggestive link between a genetic abnormality in the RYR3 gene and a neurodevelopmental disorder.