Contributory Role of Five Common Polymorphisms of RAGE and APE1 Genes in Lung Cancer among Han Chinese

Background

Lung cancer is the leading cause of cancer mortality in China. Given the ubiquitous nature of gene-to-gene interaction in lung carcinogenesis, we sought to evaluate five common polymorphisms from advanced glycosylation end product-specific receptor (RAGE) and apurinic/apyrimidinic endonuclease 1 (APE1) genes in association with lung cancer among Han Chinese.

Methods and Results

819 patients with lung cancer and 803 cancer-free controls were recruited from Qiqihar city. Genotypes of five examined polymorphisms (RAGE gene: rs1800625, rs1800624, rs2070600; APE1 gene: rs1760944, rs1130409) were determined by ligase detection reaction method. Data were analyzed by R software and multifactor dimensionality reduction (MDR). Hardy-Weinberg equilibrium was satisfied for all five polymorphisms. Overall differences in the genotype and allele distributions were significant for rs1800625 (P_genotype<0.0005; P_allele<0.0005), rs2070600 (P_genotype = 0.005; P_allele = 0.004) and rs1130409 (P_genotype = 0.009; P_allele = 0.004) polymorphisms. Haplotype C-A-A (alleles in order of rs1800625, rs1800624 and rs2070600) of RAGE gene was overrepresented in patients, and conferred a 2.1-fold increased risk of lung cancer (95% confidence interval: 1.52–2.91), independent of confounding factors. Further application of MDR method to five examined polymorphisms identified the overall best interaction model including rs2070600 and rs1130409 polymorphisms. This model had a maximal testing accuracy of 64.63% and a maximal cross-validation consistency of 9 out of 10 at the significant level of 0.006.

Conclusions

Our findings demonstrated a potential interactive contribution of RAGE and APE1 genes to the pathogenesis of lung cancer among Han Chinese. Further studies are warranted to confirm or refute these findings.     

Diversity of Cultivated and Uncultivated Actinobacterial Endophytes in the Stems and Roots of Rice

A dual approach consisting of cultivation and molecular retrieval of actinobacterial 16S rRNA genes was used to characterize the diversity of actinobacterial community inhabiting interior of rice stems and roots. Streptomyces is the most frequently isolated genus from rice stems and roots. Forty-five clones chosen randomly among 250 clones in the 16S rRNA gene clone library from roots were affiliated with nine genera of actinobacteria and uncultured actinobacteria (Mycobacterium, Streptomyces, Micromonospora, Actinoplanes, Frankia, Dactylosporangium, Amycolatopsis, Corynebacterium, Rhodococcus, and uncultured actinobacterium). However, 33 clones from stems were affiliated with four genera and uncultured actinobacteria (Streptomyces, Mycobacterium, Nocardiodies, Janibacter, uncultured earthworm cast bacterium, uncultured earthworm intestine bacterium, and uncultured actinobacterium). Species similar to S. cyaneus were isolated from surface-sterilized roots and stems of rice and detected inside rice roots by culture-independent methods. Species similar to S. caviscabies, S. scabies, and S. turgidiscabies were simultaneously detected from the interior of rice stems by the culture-dependent and culture-independent methods. S. galilaeus was detected from the interior of rice stems and roots. These results indicated that some actinobacterial populations in rice stems were correlated with those in roots. Tian and Cao contributed equally to this work     

Identification and functional characterization of pfm, a novel gene involved in swimming motility of Pseudomonas aeruginosa

Pseudomonas aeruginosa, an important opportunistic pathogen, has a single polar flagellum which is an important virulence and colonization factor by providing swimming motility. This paper describes the functional characterization of a novel gene pfm (PA2950) of P. aeruginosa. The pfm encodes a protein that is similar to a number of short-chain alcohol dehydrogenases of other bacterial species. Mutation of this gene results in a defect in swimming motility which can be completed back to that of wild type by a plasmid containing the pfm. Interestingly, the pfm mutant possesses an intact flagellum which does not rotate, thus giving rise to a non-motile phenotype. The pfm gene is encoded on an operon together with two upstream genes which code for electron transfer flavoprotein (ETF). Yeast two-hybrid tests indicated that the PFM interacts with the ETF, suggesting that the putative dehydrogenase (PFM) is involved in energy metabolism that is critical for the rotation of flagellum in P. aeruginosa.     

Effects of dissolved oxygen on survival and immune responses of scallop (Chlamys farreri Jones et Preston)

This experiment investigated the effects of dissolved oxygen (DO) on the survival and immune responses of scallop Chlamys farreri. The scallops (initial mean dry weight of soft tissue 1.52+/-0.10 g) were cultivated in the seawater with different DO levels (8.5, 6.5, 4.5, and 2.5mg l(-1), respectively) for 21 d. Each treatment had triplicate groups of 35 animals. During the experimental period, the scallops were fed with Spirulina maxima, and water temperature ranged from 15.2 degrees C to 17.5 degrees C, salinity from 29.5 per thousand to 32.5 per thousand and pH from 7.5 to 8.2. Survival, specific growth rate (SGR) and total haemocyte count (THC) were examined at the end of the study, and superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (ALP), were examined at 12 h, 24 h, Day 7, Day 14 and Day 21 after being exposed to the graded DO levels. The lower DO levels (2.5 and 4.5mg l(-1))resulted in lower survivals of scallops, and the survival (81.7%) at 2.5mg 1(-1)DO was significantly lower than those (100.0%) at 8.5 and 6.5mg l(-1) DO. Similarly, the SGR and THC of scallop gradually reduced with decreasing DO levels, and reached significant levels at 2.5mg l(-1) DO (P<0.05). At higher DO levels (8.5 and 6.5mg l(-1)), the SOD activity maintained rather stable during the entire sampling period. At lower DO levels (4.5 and 2.5mg l(-1)), however, the SOD activity significantly increased at 12 h, and then significantly decreased to the levels below the normal. At the two lower DO levels, ACP activities had no significant changes before Day 7, and then declined to the levels that were significantly lower than the normal. Significantly higher ALP activity was only observed at 12 h in the treatment of 2.5mg l(-1) DO, but in all other treatments and sampling times it fluctuated in a narrow range. In conclusion, less than 4.5mg l(-1) DO reduced the survival and depressed the immune responses of C. farreri.     

WSL6 encoding an Era-type GTP-binding protein is essential for chloroplast development in rice

Plant Molecular Biology - Rice WSL6 is involved in chloroplast ribosome biogenesis and is essential for early chloroplast development. Construction of the genetic translation system is a...     

Source-sink manipulation effects on postanthesis photosynthesis and grain setting on spike in winter wheat

Source-sink manipulation could regulate the net photosynthetic rate (PN) of winter wheat after anthesis, however, the direction and magnitude of the regulation varied with time after anthesis. The PN was significantly increased by source reduction at the initial time of grain filling, but sink reduction had little influence on the PN, which suggested that the sink (spike) limitation did not occur at this time. Source-sink relation markedly affected PN during rapid grain filling. The PN was increased by source reduction and decreased by sink reduction significantly, which indicated that PN was closely associated with the change of source or sink size. The effect of source-sink manipulation on PN had some relationship with the occurrence of plant senescence at the time of late grain filling. Source reduction accelerated the senescence and dropped the PN, meanwhile, sink reduction delayed the senescence and promoted the PN. A direct relation between the effect of source-sink manipulation on PN and stomatal limitation was not found. Removing one quarter of leaves (RQ) had little influence on spike development after anthesis. In this case there was enough compensation in source production through photosynthesis. Removing one half of leaves (RH) made grain mass per spike and mass of grains lowered, especially the grain mass in the top and base positions of spike declined markedly. The source supply was grain-limiting. Removing one quarter of spikelets (RS) was beneficial to grain-setting in the remaining spikelets, leading to the increase of grain mass. Thus promoting the source supply of photosynthates after anthesis is of major importance for grain to set and to develop.     

EGFR tyrosine kinase inhibitors activate autophagy as a cytoprotective response in human lung cancer cells

Epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib have been widely used in patients with non-small-cell lung cancer. Unfortunately, the efficacy of EGFR-TKIs is limited because of natural and acquired resistance. As a novel cytoprotective mechanism for tumor cell to survive under unfavorable conditions, autophagy has been proposed to play a role in drug resistance of tumor cells. Whether autophagy can be activated by gefitinib or erlotinib and thereby impair the sensitivity of targeted therapy to lung cancer cells remains unknown. Here, we first report that gefitinib or erlotinib can induce a high level of autophagy, which was accompanied by the inhibition of the PI3K/Akt/mTOR signaling pathway. Moreover, cytotoxicity induced by gefitinib or erlotinib was greatly enhanced after autophagy inhibition by the pharmacological inhibitor chloroquine (CQ) and siRNAs targeting ATG5 and ATG7, the most important components for the formation of autophagosome. Interestingly, EGFR-TKIs can still induce cell autophagy even after EGFR expression was reduced by EGFR specific siRNAs. In conclusion, we found that autophagy can be activated by EGFR-TKIs in lung cancer cells and inhibition of autophagy augmented the growth inhibitory effect of EGFR-TKIs. Autophagy inhibition thus represents a promising approach to improve the efficacy of EGFR-TKIs in the treatment of patients with advanced non-small-cell lung cancer.     

外源NO对铝毒下水稻根系生长和抗氧化系统的影响

以水稻品种‘浙辐802’为材料,采用水培法研究铝毒下外源NO对幼苗根系生长、活性氧产生和抗氧化酶活性的影响,探讨外源NO提高水稻耐铝性的生理生化机制。结果显示:(1)0.05mmol/L Al显著抑制水稻根系生长,促使根尖Al、胼胝质、过氧化氢(H2O2)和超氧阴离子自由基(O-·2)含量显著增加;而外源0.1mmol/L的NO供体亚硝基铁氰化钠(sodium nitroprusside,SNP)预处理能使铝毒下水稻幼苗根相对伸长率及根尖NO含量分别增加34.96%和12.86%,根尖Al和相对胼胝质含量分别下降83.04%和31.93%,表明NO可部分缓解铝毒害,且这种作用与内源NO含量变化有关。(2)外源NO同时使铝毒下水稻幼苗根尖H2O2和O-·2含量分别下降15.43%和12.93%,使超氧化物歧化酶(SOD)、过氧化物酶(POD)和过氧化氢酶(CAT)活性显著上升,且外源NO的该种作用可以被0.075mmol/L NO清除剂(carboxy-PTIO,cPTIO)所逆转。研究表明,外源NO在调节活性氧代谢以维持细胞膜结构稳定,进而有效减轻Al对水稻根系的损伤上起着重要作用。     

CRISPR/Cas9-mediated knockout of myostatin in Chinese indigenous Erhualian pigs

CRISPR/Cas9 has emerged as one of the most popular genome editing tools due to its simple design and high efficiency in multiple species. Myostatin (MSTN) negatively regulates skeletal muscle growth and mutations in myostatin cause double-muscled phenotype in various animals. Here, we generated myostatin mutation in Erhualian pigs using a combination of CRISPR/Cas9 and somatic cell nuclear transfer. The protein level of myostatin precursor decreased dramatically in mutant cloned piglets. Unlike myostatin knockout Landrace, which often encountered health issues and died shortly after birth, Erhualian pigs harboring homozygous mutations were viable. Moreover, myostatin knockout Erhualian pigs exhibited partial double-muscled phenotype such as prominent muscular protrusion, wider back and hip compared with wild-type piglets. Genome editing in Chinese indigenous pig breeds thus holds great promise not only for improving growth performance, but also for protecting endangered genetic resources.