Support vector machine for classification of meiotic recombination hotspots and coldspots in Saccharomyces cerevisiae based on codon composition

BACKGROUND: Meiotic double-strand breaks occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots). Hotspots and coldspots are receiving increasing attention in research into the mechanism of meiotic recombination. However, predicting hotspots and coldspots from DNA sequence information is still a challenging task. RESULTS: We present a novel method for classification of hot and cold ORFs located in hotspots and coldspots respectively in Saccharomyces cerevisiae, using support vector machine (SVM), which relies on codon composition differences. This method has achieved a high classification accuracy of 85.0%. Since codon composition is a fusion of codon usage bias and amino acid composition signals, the ability of these two kinds of sequence attributes to discriminate hot ORFs from cold ORFs was also investigated separately. Our results indicate that neither codon usage bias nor amino acid composition taken separately performed as well as codon composition. Moreover, our SVM based method was applied to the full genome: We predicted the hot/cold ORFs from the yeast genome by using cutoffs of recombination rate. We found that the performance of our method for predicting cold ORFs is not as good as that for predicting hot ORFs. Besides, we also observed a considerable correlation between meiotic recombination rate and amino acid composition of certain residues, which probably reflects the structural and functional dissimilarity between the hot and cold groups. CONCLUSION: We have introduced a SVM-based novel method to discriminate hot ORFs from cold ones. Applying codon composition as sequence attributes, we have achieved a high classification accuracy, which suggests that codon composition has strong potential to be used as sequence attributes in the prediction of hot and cold ORFs

N6-Methyladenosine and Viral Infection

N6-methyladenosine (m6A), as a dynamic posttranscriptional RNA modification, recently gave rise to the field of viral epitranscriptomics. The interaction between virus and host is affected by m6A. Multiple m6A-modified viral RNAs have been observed. The epitranscriptome of m6A in host cells are altered after viral infection. The expression of viral genes, the replication of virus and the generation of progeny virions are influenced by m6A modifications in viral RNAs during virus infection. Meanwhile, the decorations of m6A in host mRNAs can make viral infections more likely to happen or can enhance the resistance of host to virus infection. However, the mechanism of m6A regulation in viral infection and host immune response has not been thoroughly elucidated to date. With the development of sequencing-based biotechnologies, transcriptome-wide mapping of m6A in viruses has been achieved, laying the foundation for expanding its functions and corresponding mechanisms. In this report, we summarize the positive and negative effects of m6A in distinct viral infection. Given the increasingly important roles of m6A in diverse viruses, m6A represents a novel potential target for antiviral therapy

Efficacy and safety of a NiTi CAR 27 compression ring for end-to-end anastomosis compared with conventional staplers: A real-world analysis in Chinese colorectal cancer patients

OBJECTIVES: This study aimed to evaluate the safety and efficacy of a new nickel-titanium shape memory alloy compression anastomosis ring, NiTi CAR 27, in constructing an anastomosis for colorectal cancer resection compared with conventional staples. METHODS: In total, 234 consecutive patients diagnosed with colorectal cancer receiving sigmoidectomy and anterior resection for end-to-end anastomosis from May 2010 to June 2012 were retrospectively analyzed. The postoperative clinical parameters, postoperative complications and 3-year overall survival in 77 patients using a NiTi CAR 27 compression ring (CAR group) and 157 patients with conventional circular staplers (STA group) were compared. RESULTS: There were no statistically significant differences between the patients in the two groups in terms of general demographics and tumor features. A clinically apparent anastomotic leak occurred in 2 patients (2.6%) in the CAR group and in 5 patients (3.2%) in the STA group (p=0.804). These eight patients received a temporary diverting ileostomy. One patient (1.3%) in the CAR group was diagnosed with anastomotic stricture through an electronic colonoscopy after 3 months postoperatively. The incidence of postoperative intestinal obstruction was comparable between the two groups (p=0.192). With a median follow-up duration of 39.6 months, the 3-year overall survival rate was 83.1% in the CAR group and 89.0% in the STA group (p=0.152). CONCLUSIONS: NiTi CAR 27 is safe and effective for colorectal end-to-end anastomosis. Its use is equivalent to that of the conventional circular staplers. This study suggests that NiTi CAR 27 may be a beneficial alternative in colorectal anastomosis in Chinese colorectal cancer patients

Myelin Activates FAK/Akt/NF-κB Pathways and Provokes CR3-Dependent Inflammatory Response in Murine System

Inflammatory response following central nervous system (CNS) injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), there has been very little study of the direct inflammatory consequences of damaged myelin in spinal cord injury (SCI), i.e., there is no direct evidence to show that myelin debris from injured spinal cord can trigger undesirable inflammation in vitro and in vivo. Our data showed that myelin can initiate inflammatory responses in vivo, which is complement receptor 3 (CR3)-dependent via stimulating macrophages to express pro-inflammatory molecules and down-regulates expression of anti-inflammatory cytokines. Mechanism study revealed that myelin-increased cytokine expression is through activation of FAK/PI3K/Akt/NF-κB signaling pathways and CR3 contributes to myelin-induced PI3K/Akt/NF-κB activation and cytokine production. The myelin induced inflammatory response is myelin specific as sphingomyelin (the major lipid of myelin) and myelin basic protein (MBP, one of the major proteins of myelin) are not able to activate NF-κB signaling pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating SCI

Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >;7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >;7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response

In-vitro and in-vivo phenotype of type Asia 1 foot-and-mouth disease viruses utilizing two non-RGD receptor recognition sites

<p>Abstract</p> <p>Background</p> <p>Foot-and-mouth disease virus (FMDV) uses a highly conserved Arg-Gly-Asp (RGD) triplet for attachment to host cells and this motif is believed to be essential for virus viability. Previous sequence analyses of the 1D-encoding region of an FMDV field isolate (Asia1/JS/CHA/05) and its two derivatives indicated that two viruses, which contained an Arg-Asp-Asp (RDD) or an Arg-Ser-Asp (RSD) triplet instead of the RGD integrin recognition motif, were generated serendipitously upon short-term evolution of field isolate in different biological environments. To examine the influence of single amino acid substitutions in the receptor binding site of the RDD-containing FMD viral genome on virus viability and the ability of non-RGD FMDVs to cause disease in susceptible animals, we constructed an RDD-containing FMDV full-length cDNA clone and derived mutant molecules with RGD or RSD receptor recognition motifs. Following transfection of BSR cells with the full-length genome plasmids, the genetically engineered viruses were examined for their infectious potential in cell culture and susceptible animals.</p> <p>Results</p> <p>Amino acid sequence analysis of the 1D-coding region of different derivatives derived from the Asia1/JS/CHA/05 field isolate revealed that the RDD mutants became dominant or achieved population equilibrium with coexistence of the RGD and RSD subpopulations at an early phase of type Asia1 FMDV quasispecies evolution. Furthermore, the RDD and RSD sequences remained genetically stable for at least 20 passages. Using reverse genetics, the RDD-, RSD-, and RGD-containing FMD viruses were rescued from full-length cDNA clones, and single amino acid substitution in RDD-containing FMD viral genome did not affect virus viability. The genetically engineered viruses replicated stably in BHK-21 cells and had similar growth properties to the parental virus. The RDD parental virus and two non-RGD recombinant viruses were virulent to pigs and bovines that developed typical clinical disease and viremia.</p> <p>Conclusions</p> <p>FMDV quasispecies evolving in a different biological environment gained the capability of selecting different receptor recognition site. The RDD-containing FMD viral genome can accommodate substitutions in the receptor binding site without additional changes in the capsid. The viruses expressing non-RGD receptor binding sites can replicate stably in vitro and produce typical FMD clinical disease in susceptible animals.</p