The CircRNA-ACAP2/Hsa-miR-21-5p/ Tiam1 Regulatory Feedback Circuit Affects the Proliferation, Migration, and Invasion of Colon Cancer SW480 Cells

Background/Aims: Circular RNAs (circRNAs), a type of RNA that is widely expressed in human cells, have essential roles in the development and progression of cancer. CircRNAs contain microRNA (miRNA) binding sites and can function as miRNA sponges to regulate gene expression by removing the inhibitory effect of an miRNA on its target gene. Methods: We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNAi-Mrna interactions. Rate of inhibiting of proliferation was measured using a WST-8 cell proliferation assay. Clone formation ability was assessed with a clone formation inhibition test. Cell invasion and migration capacity was evaluated by performing a Transwell assay. Relative gene expression was assessed using quantitative real-time polymerase chain reaction and relative protein expression levels were determined with western blotting. circRNA and miRNA interaction was confirmed by dual-luciferase reporter and RNA-pull down assays. Results: In the present study, the miRNA hsa-miR-21-5p was a target of circRNA-ACAP2, and T lymphoma invasion and metastasis protein 1 (Tiam1) was identified as a target gene of hsa-miR-21-5p. CircRNA-ACAP2 and Tiam1 were shown to be highly expressed in colon cancer tissue and colon cancer SW480 cells, but miR-21-5p was expressed at a low level. SW480 cell proliferation was suppressed when the expression of circRNA-ACAP2 and Tiam1 was decreased and the expression of miR-21-5p was increased in vivo and in vitro. SW480 cell migration and invasion were also inhibited under the same circumstance. The circRNA-ACAP2 interaction regulated the expression of miR-21-5p, and miR-21-5p regulated the expression of Tiam1. Down-regulation of circRNA-ACAP2 promoted miR-21-5p expression, which further suppressed the transcription and translation of Tiam1. Conclusion: The present study shows that the circRNA-ACAP2/hsa-miR-21-5p/Tiam1 regulatory feedback circuit could affect the proliferation, migration, and invasion of colon cancer SW480 cells. This was probably due to the fact that circRNA-ACAP2 could act as a miRNA sponge to regulate Tiam1 expression by removing the inhibitory effect of miR-21-5p on Tiam1 expression. The results from this study have revealed new insights into the pathogenicity of colon cancer and may provide novel therapeutic targets for the treatment of colon cancer

An Observational Study of the Relationship Between Outcome and Platelet Reactivity in Chinese Patients Undergoing PCI Loading with 600 mg Clopidogrel

Objectives: We sought to determine whether high posttreatment platelet reactivity (HPPR) to a 600 mg loading dose of clopidogrel affects outcomes in Chinese patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) and to investigate whether there is a relationship between the number of platelet reactivity units (PRUs) and the characteristics of the patients. Background: Although impaired platelet response to clopidogrel is a strong predictor of unfavorable outcome after PCI, the impact of HPPR to a 600 mg loading dose of clopidogrel in Chinese patients with ACS undergoing PCI is still unknown. Methods: We performed observational research on 134 unselected patients with ACS undergoing urgent or planned PCI with a 600 mg loading dose of clopidogrel. Platelet activation was expressed as the PRU value measured by the VerifyNow assay. Results: Among the 134 patients (mean age 60.62 years [standard deviation 9.13 years], 60.4% male), there were 46 patients with HPPR (34.3%) and 88 patients without HPPR (65.7%). At a mean follow-up of 6 months (standard deviation 1 month), the rates of cardiac death, unstable angina, and rehospitalization for target lesion revascularization were higher in the HPPR group (19.6% vs. 6.8%, P=0.029). Multivariate analysis identified hemoglobin level and sex as independent predictors of the PRU value ( y =456.355−1.736 x 1 −31.880 x 2 , P<0.05). On receiver operating characteristic curve analysis, PRU values could significantly discriminate between patients with and patients without cardiac death, unstable angina, and rehospitalization for target lesion revascularization (area under the curve 0.758, 95% confidence interval 0.62–0.85, P=0.001, P<0.05). Conclusion: In patients with ACS, HPPR to a 600 mg loading dose of clopidogrel is associated with worse outcomes after PCI. There is some relationship between the PRU value and the hemoglobin level and sex. PRU values can predict the prognosis

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation

Paternal Origins and Migratory Episodes of Domestic Sheep

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution

Historical Introgression from Wild Relatives Enhanced Climatic Adaptation and Resistance to Pneumonia in Sheep

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667–248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication

Paternal origins and migratory episodes of domestic sheep.

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution

Effects of Dietary Protein and Energy Levels on Growth, Feed utilization and Body Composition of Skin Carp Hemibarbus labeo

A 12-week feeding trial was conducted to assess the effects of dietary protein and energy levels on the growth, feed utilization, and body composition of skin carp Hemibarbus labeo. Ten experimental diets with five levels of crude protein (CP) and two levels of crude lipid (CL) were designated as 32%, 36%, 40%, 44%, 48% and 18 MJ/kg,19.5MJ/kg, respectively. Final body weight (FBW) and weight gain rate (WGR) increased, whereas the feed intake (FI) and feed conversion ratio (FCR) decreased, with increasing dietary protein level from 32% to 48%. Fish fed the diets containing 44% CP and CL providing 19.5MJ/kg exhibited higher FBW and WGR, but lower FI and FCR. At the end of the feeding trial, the intraperitoneal fat ratio (IPFR) decreased with the increase of CP levels. Significant differences (P<0.05) were found in the carcass composition of fish fed different levels of CP and CL. No noticeable trend was observed for moisture and ash in the carcass. The optimum CP and CL level were found to be 44% and 19.5MJ/kg respectively for skin carp reared in net cages

Comparing deposition of organic and inorganic siloxane films by the atmospheric pressure glow discharge

National Natural Science Foundation of China [10735090, 11005151]The atmospheric pressure glow discharge burning in argon with small admixture of oxygen and hexamethyldisiloxane is used for the deposition of organosilicon and SiOx-like films on the stainless steel surface. The organosilicon film has high growth rate (85 nm/min) and extremely low surface roughness (0.8 nm), while the SiOx-like film shows relatively low growth rate (40 nm/min) and higher surface roughness (9 nm). The surface wettability, microhardness and the corrosion resistance of the deposited siloxane films are detected. The organosilicon film is hydrophobic (contact angle: 98 degrees) and soft (microhardness: 0.68 GPa), while the SiOx-like film is hydrophilic (contact angle: 45 degrees) and hard (microhardness: 7.85 GPa). The potentiodynamic polarization tests show that by depositing siloxane films on the surface, the corrosion resistance of the stainless steel in the Hanks solution can be largely improved. In particular, the SiOx-like film exhibits better corrosion resistance than the organosilicon film. (C) 2011 Elsevier B.V. All rights reserved

Lack of association between the CHL1 gene and adolescent idiopathic scoliosis susceptibility in Han Chinese: a case-control study

BACKGROUND: A previous genome-wide association study (GWAS) suggested a strong association between the single nucleotide polymorphism (SNP) rs10510181 in the proximity of the gene encoding a cell adhesion molecule with homology to L1CAM (CHL1) and adolescent idiopathic scoliosis (AIS) in Caucasians. To clarify the role of CHL1 in the etiopathogenesis of AIS, we performed a case-control replication study in a Han Chinese population. METHODS: Five hundred female AIS patients between 10 and 18 years of age, as well as 500 age- and sex-matched controls were included. This study was conducted as a 2-stage case-control analysis: initial screening for the association between AIS and SNPs in and around the CHL1 gene (186 cases and 169 controls) followed by a confirmation test (314 cases and 331 controls). rs10510181 and 4 SNPs (rs2055314, rs331894, rs2272522, and rs2272524) in the CHL1 gene were selected for genotyping. RESULTS: Putative associations were shown between AIS and rs10510181, rs2055314, and rs2272522 in stage I. However, the associations were not confirmed in stage II. For rs10510181, the genotype frequencies were GG 28.8%, GA 46.2%, and AA 25.0% in AIS patients and GG 29.8%, GA 48.8%, and AA 21.4% in controls. No significant difference was found in genotype distribution between cases and controls (P = 0.39). Similarly, the genotype and allele distribution were comparable between case and control for rs2055314 and rs2272522. CONCLUSIONS: There was no statistical association between polymorphisms of the CHL1 gene and idiopathic scoliosis in a Chinese population