Description: Background: Degradation is essential for RNA maturation, turnover, and quality control. RNA degradome sequencing that integrates a modified 5[prime]-rapid amplification of cDNA ends protocol with next-generation sequencing technologies is a high-throughput approach for profiling the 5[prime]-end of uncapped RNA fragments on a genome-wide scale. The primary application of degradome sequencing has been to identify the truncated transcripts that result from endonucleolytic cleavage guided by microRNAs or small interfering RNAs. As many pathways are involved in RNA degradation, degradome data should contain other RNA species besides the cleavage remnants of small RNA targets. Nevertheless, no systematic approaches have been established to explore the hidden complexity of plant degradome. Results: Through analyzing Arabidopsis and rice RNA degradome data, we recovered 11 short motifs adjacent to predominant and abundant uncapped 5[prime]-ends. Uncapped ends associated with several of these short motifs were more prevalent than those targeted by most miRNA families especially in the 3[prime] untranslated region of transcripts. Through genome-wide analysis, five motifs showed preferential accumulation of uncapped 5[prime]-ends at the same position in Arabidopsis and rice. Moreover, the association of uncapped 5[prime]-ends with a CA-repeat motif and a motif recognized by Pumilio/Fem-3 mRNA binding factor (PUF) proteins was also found in non-plant species, suggesting that common mechanisms are present across species. Based on these motifs, potential sources of RNA ends that constitute degradome data were proposed and further examined. The 5[prime]-end of small nucleolar RNAs could be precisely captured by degradome sequencing. Position-specific enrichment of uncapped 5[prime]-ends was seen upstream of motifs recognized by several RNA binding proteins especially for the binding site of PUF proteins. False uncapped 5[prime]-ends produced from capped transcripts through non-specific PCR amplification were common artifacts among degradome datasets. Conclusions: The complexity of plant RNA degradome data revealed in this study may contribute to the alternative applications of degradome in RNA research.

Description: Chinese tradition and culture developed from Taoism, Confucianism, and Buddhism and have influenced ethnic Chinese for thousands of years, particularly thoughts on death. Many ethnic Chinese, particularly olde...

Description: Background: Diabetes mellitus (DM) has been associated with the cancer risk. This study investigated relationship between DM and esophageal cancer using Taiwan's insurance data. Methods: We identified 549 patients with esophageal cancer newly diagnosed in 2000-2009 and randomly selected 2196 controls without any cancer, frequency matched by sex, age and diagnosis year of cases. Logistic regression model estimated odds ratios (ORs) and 95% confidence intervals (CI) of esophageal cancer associated with DM, sex, age. co-morbidities and medications. Results: Cases were more prevalent than controls for alcoholism and esophageal disorders and using nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 inhibitors but not DM. Esophageal cancer had no association with DM (OR 0.99, 95% CI 0.71-1.37), but significantly associated with alcoholism (OR 14.1, 95% CI 7.87-25.4), esophageal ulcer (OR 10.1, 95% CI 5.70-17.9), esophageal reflux (OR 3.47, 95% CI 2.14-5.26) and uses of NSAIDs (OR 2.73, 95% CI 1.80-4.13). An elevated risk of esophageal cancer appeared in DM patients taking insulin (OR 2.57, 95% CI 1.08-6.15) or sulfonyurea (OR 3.80, 95% CI 1.16-12.5). Conclusions: Patients with DM are not at higher risk for esophagus cancer. However, esophageal disorders and anti-diabetic drugs are associated with the risk of the disease.

Description: Background: The aims of this study were to evaluate the antioxidant activity and to identify the antioxidant components of a traditional Chinese medicine formula consisting of a combination of Shanzha (the fruit of Crataegus pinnatifida Bge. var. major N.E.Br., SZ) and Danshen (the root of Salvia miltiorrhiza Bge., DS). This medicine is extensively used to treat cardiovascular disease. Methods: Twelve samples extracted and fractionated from SZ, DS and the formula (SZ+DS) were analyzed. The concentrations of eight phenolic compounds were determined by high performance liquid chromatography. Oxygen radical absorbance capacity (ORAC) assay and 1,1-diphenyl-2-picrylhydrazyl assay were conducted to explore the antioxidant activities of the samples and of the 15 phenolic compounds detected. Correlation analysis of the antioxidant activity of herb samples and their phenolic components was performed. Results: The main phenolic component in all SZ+DS samples was salvianolic acid B, which exhibited strong antioxidant activity (ORAC value: 16.73 +/- 2.53, IC50 value: 8.80 +/- 0.06 muM) compared with the other phenolic compounds. For all samples, there was a positive relationship between their total phenolic components and their antioxidant activities. Conclusions: Phenolic compounds were the bioactive components of the herb samples, and salvianolic acid B was identified as the main bioactive compound in the SZ+DS formula.

Description: Cancers, Vol. 10, Pages 13: Translocation Breakpoints Preferentially Occur in Euchromatin and Acrocentric Chromosomes Cancers doi: 10.3390/cancers10010013 Authors: Cheng-Yu Lin Ankit Shukla John Grady J. Fink Eloise Dray Pascal Duijf Chromosomal translocations drive the development of many hematological and some solid cancers. Several factors have been identified to explain the non-random occurrence of translocation breakpoints in the genome. These include chromatin density, gene density and CCCTC-binding factor (CTCF)/cohesin binding site density. However, such factors are at least partially interdependent. Using 13,844 and 1563 karyotypes from human blood and solid cancers, respectively, our multiple regression analysis only identified chromatin density as the primary statistically significant predictor. Specifically, translocation breakpoints preferentially occur in open chromatin. Also, blood and solid tumors show markedly distinct translocation signatures. Strikingly, translocation breakpoints occur significantly more frequently in acrocentric chromosomes than in non-acrocentric chromosomes. Thus, translocations are probably often generated around nucleoli in the inner nucleoplasm, away from the nuclear envelope. Importantly, our findings remain true both in multivariate analyses and after removal of highly recurrent translocations. Finally, we applied pairwise probabilistic co-occurrence modeling. In addition to well-known highly prevalent translocations, such as those resulting in BCR-ABL1 (BCR-ABL) and RUNX1-RUNX1T1 (AML1-ETO) fusion genes, we identified significantly underrepresented translocations with putative fusion genes, which are probably subject to strong negative selection during tumor evolution. Taken together, our findings provide novel insights into the generation and selection of translocations during cancer development.

Description: Background: Chronic kidney disease (CKD) is more prevalent in Taiwan than in most countries. This population-based cohort study evaluated the dementia risk associated with CKD. Methods: Using claims data of 1,000,000 insured residents covered in the universal health insurance of Taiwan, we selected 37049 adults with CKD newly diagnosed from 2000--2006 as the CKD cohort. We also randomly selected 74098 persons free from CKD and other kidney diseases, frequency matched with age, sex and the date of CKD diagnosed. Incidence and hazard ratios (HRs) of dementia were evaluated by the end of 2009. Results: Subjects in the CKD cohort were more prevalent with comorbidities than those in the non-CKD cohort (p

Description: Background: Phosphatase of regenerating liver (PRL) family is classified as class IVa of protein tyrosine phosphatase (PTP4A) that removes phosphate groups from phosphorylated tyrosine residues on proteins. PRL phosphatases have been implicated in a number of tumorigenesis and metastasis processes and are highly conserved. However, the understanding of PRL expression profiles during embryonic development is very limited. Results: In this study, we demonstrated and characterized the comprehensive expression pattern of Drosophila PRL, amphioxus PRL, and zebrafish PRLs during embryonic development by either whole mount immunostaining or in situ hybridization. Our results indicate that Drosophila PRL is mainly enriched in developing mid-guts and central nervous system (CNS) in embryogenesis. In amphioxus, initially PRL gene is expressed ubiquitously during early embryogenesis, but its expression become restricted to the anterior neural tube in the cerebral vesicle. In zebrafish, PRL-1 and PRL-2 share similar expression patterns, most of which are neuronal lineages. In contrast, the expression of zebrafish PRL-3 is more specific and preferential in muscle. Conclusions: This study, for the first time, elucidated the embryonic expression pattern of Drosophila, amphioxus, and zebrafish PRL genes. The shared PRL expression pattern in the developing CNS among diverse animals suggests that PRL may play conserved roles in these animals for CNS development.

Description: Background: To compare the value of ultrasonography for diagnosing carpal tunnel syndrome (CTS) in patients with and without diabetes mellitus (DM). Methods: Eighty non-DM and 40 DM patients with electromyography-confirmed CTS were assessed and underwent high-resolution ultrasonography of the wrists. Cross-sectional area (CSA) and flattening ratio (FR) of the median nerve were measured at the carpal tunnel outlet (D) and wrist crease (W). Results: The 80 non-DM and 40 DM patients had 81 and 59 CTS-hands, respectively. The CSA_D and CSA_W were significantly larger in the CTS-hands and DM-CTS-hands compared to the normal control (p 〈 0.001). However, there is no difference of CSA_D and CSA_W between DM and non-DM CTS patients. Receiver operating characteristics [ROC] curve analysis revealed that CSA_W 〉=13 mm2 was the most powerful predictor of CTS in DM (area under curve [AUC] = 0.72; sensitivity 72.9%, specificity 61.9%) and non-DM (AUC = 0.72; sensitivity 78.5%, specificity 53.2%) patients. The CSA positively correlated with the distal motor latency of the median compound motor action potential (CMAP), distal sensory latency of the median sensory nerve action potential (SNAP), and latency of the median F wave, but negatively correlated with the amplitude of the median CMAP, amplitude of the median SNAP, and sensory NCV of the median nerve. Stepwise logistic regression revealed that CSA_W (OR 1.21, 95% CI 1.07-1.38; p = 0.003) was independently associated with CTS in DM patients and any 1 mm2 increase in CSA_W increased the rate of CTS by 28%. Conclusions: The CSA of the median nerve at the outlet and wrist crease are significantly larger in CTS hands in both DM and non-DM patients compared to normal hands. The CSA of the median nerve by ultrasonography may be a diagnostic tool for evaluating CTS in DM and non-DM patients.

Description: Background: Increasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. However, clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited. Methods: A retrospective observational cohort study of all hospitalized adult patients treated with daptomycin (〉 6 mg/kg) for at least 72 hours was performed in Taiwan. Results: A total of 67 patients (40 males) with a median age of 57 years received a median dose of 7.61 mg/kg (range, 6.03-11.53 mg/kg) of daptomycin for a median duration of 14 days (range, 3--53 days). Forty-one patients (61.2%) were in intensive care units (ICU). Sites of infections included complicated skin and soft tissue infections (n= 16), catheter-related bacteremia (n= 16), endocarditis (n= 11), primary bacteremia (n= 10), osteomyelitis and septic arthritis (n=9), and miscellaneous (n= 5). The median Pitt bacteremia score among the 54 (80.6%) patients with bacteremia was 4. The most common pathogen was methicillin-resistant Staphylococcus aureus (n=38). Fifty-nine patients (88.1%) were treated with daptomycin after glycopepetide use. Overall, 52 (77.6%) patients achieved clinical success. The all-cause mortality rate at 28 day was 35.8%. In multivariate analysis, the significant predictors of in-hospital mortality in 54 bacteremic patients were malignancies (P = 0.01) and ICU stay (P = 0.02). Adverse effects of daptomycin were generally well-tolerated, leading to discontinuation in 3 patients. Daptomycin-related creatine phosphokinase (CPK) elevations were observed in 4 patients, and all received doses 〉 8 mg/kg. Conclusions: Treatment with high dose daptomycin as salvage therapy was generally effective and safe in Taiwan. CPK level elevations were more frequent in patients with dose 〉 8 mg/kg.

Description: Background: Diwu Yanggan (DWYG) is a Chinese compound herbal preparation which consists of five Chinese herbs. This study investigates the preventative effects of DWYG on liver fibrosis induced by carbon tetrachloride (CCl4) and explores its possible mechanisms of action. Methods: Liver fibrosis was induced in male Wistar rats by injecting a 50% CCl4/soybean oil solution subcutaneously twice a week for six weeks. After six weeks of treatment, serum aspartate transaminase (AST) and alanine transaminase (ALT) assay, liver tissue histological assessment and hepatic hydroxyproline assay were respectively carried out to examine the effects of DWYG on liver function and fibrosis degree. The impacts of DWYG on the expression levels of epithelial marker E-cadherin, mesenchymal marker Vimentin, transforming growth factor beta1 (TGF-beta1) and bone morphogenetic protein-7 (BMP-7) were further examined by quantitative real-time RT-PCR and Western blot analysis. In addition, the differences of Hedgehog (Hh) signaling pathway activity between DWYG-treated and DWYG-untreated fibrotic liver tissues were also evaluated by quantitative real-time RT-PCR and Western blot analysis. Results: Upon DWYG treatment, the serum levels of ALT and AST, hepatic hydroxyproline content and the degree of fibrosis in CCl4-induced fibrotic model rats were dramatically declined. In accompany with the alleviation of the degree of fibrosis, DWYG treatment provoked the reversal of epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) in the fibrotic liver tissues, which was characterized with the up-regulation expression of E-cadherin and down-regulation expression of Vimentin. Furthermore, we observed that the expression level of TGF-beta1 was reduced whereas the expression level of BMP-7 was enhanced in liver tissues of DWYG-treated rats, therefore the expression ratio of TGF-beta1/BMP-7 was dramatically decreased compared to CCl4-induced fibrosis model rats. In addition, quantitative real-time RT-PCR and Western blot analysis demonstrated that after DWYG treatment the expressions of Hh ligand Shh, receptor Smo and Ptc, and transcription factor Gli1 in CCl4-induced fibrotic liver tissues were dramatically repressed. Conclusions: DWYG demonstrates therapeutic potential to prevent liver fibrosis by modulating the balance between EMT and MET through reducing the expression ratio of TGF-beta1/BMP-7 and inhibiting the excessive activation of Hh signaling pathway.