Description: Experimental studies showed that 25-hydroxy-vitamin D [25(OH)D] deficiency (defined as 25-hydroxy-vitamin D 

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: 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.

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: Official guidelines recommend palliative treatments for patients with liver metastases from gastric cancer. However, many case series reported that hepatectomy for such cases is safe and effective. This system...

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: IntroductionIndividual recognition and winner/loser effects both play important roles in animal contests, but how their influences are integrated to affect an individual?s contest decisions in combination remains unclear. Individual recognition provides an animal with relatively precise information about its ability to defeat conspecifics that it has fought previously. Winner/loser effects, conversely, rely on sampling information about how an animal?s ability to win compares with those of others in the population. The less precise information causing winner/loser effects should therefore be more useful to an individual facing an unfamiliar opponent. In this study, we used Kryptolebias marmoratus, a hermaphroditic mangrove killifish, to test whether winner/loser effects do depend on opponent familiarity. In addition, as previous studies have shown that subordinates that behave aggressively sometimes suffer post-retreat retaliation from contest winners, we also explored this aspect of contest interaction in K. marmoratus. Results: In the early stages of a contest, subordinates facing an unfamiliar dominant were more likely to signal their aggressiveness with either gill displays or attacks rather than retreating immediately. A winning experience then increased the likelihood that the most aggressive behavioral pattern the subordinates exhibited would be attacks rather than gill displays, irrespective of their opponents? familiarity. Dominants that received a losing experience and faced an unfamiliar opponent were less likely than others to launch attacks directly. And subordinates that challenged dominants with more aggressive tactics but still lost received more post-retreat attacks from their dominant opponents. Conclusions: Subordinates? contest decisions were influenced by both their contest experience and the familiarity of their opponents, but these influences appeared at different stages of a contest and did not interact significantly with each other. The influence of a losing experience on dominants? contest decisions, however, did depend on their subordinate opponents? familiarity. Subordinates and dominants thus appeared to integrate information from the familiarity of their opponents and the outcome of previous contests differently, which warrants further investigation. The higher costs that dominants imposed on subordinates that behaved more aggressively toward them may have been to deter them from either fighting back or challenging them in the future.

Description: Background: Early diagnosis and treatment of nontuberculous mycobacterial lung diseases (NTM-LD) and pulmonary tuberculosis (PTB) are important clinical issues. The present study aimed to compare and identify the chest CT characteristics that help to distinguish NTM lung disease from PTB in patients with acid-fast bacilli (AFB) smear-positive sputum. Methods: From January 2009 to April 2012, we received 467 AFB smear-positive sputum specimens. A total of 95 CT scans obtained from the 159 patients were analyzed, 75 scans were from patients with PTB and 20 scans from NTM-LD. The typical chest CT findings of mycobacterial diseases were analyzed. Results: In patients with PTB, the prevalence of pleural effusion (38.7% vs. 15.0%; P =0.047), nodules 〈 10 mm in size (76.0% vs. 25.0%; P 〈 0.001), tree-in-bud pattern (81.3% vs. 55.0%; P =0.021), and cavities (31.1% vs. 5.0%; P =0.018) were significantly higher than patients with NTM. Of the 20 patients with NTM lung diseases, bronchiectasis and cystic changes were significantly higher than patients with PTB (20.0% vs. 4.0%; P = 0.034). In multivariate analysis, CT scan findings of nodules was independently associated with patients with diagnoses of PTB (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.02-0.30). Presence of bronchiectasis and cystic changes in CT scans was strongly associated with patients with NTM-LD (OR, 33.04; 95% CI, 3.01-362.55). Conclusions: The CT distinction between NTM-LD and PTB may help radiologists and physicians to know the most likely diagnoses in AFB-smear positive patients and avoid unnecessary adverse effects and the related costs of anti-TB drugs in endemic areas.

Description: Background: Microbial diversity and community structures in acidic hot springs have been characterized by 16S rRNA gene-based diversity surveys. However, our understanding regarding the interactions among microbes, or between microbes and environmental factors, remains limited. Results: In the present study, a metagenomic approach, followed by bioinformatics analyses, were used to predict interactions within the microbial ecosystem in Shi-Huang-Ping (SHP), an acidic hot spring in northern Taiwan. Characterizing environmental parameters and potential metabolic pathways highlighted the importance of carbon assimilatory pathways. Four distinct carbon assimilatory pathways were identified in five dominant genera of bacteria. Of those dominant carbon fixers, Hydrogenobaculum bacteria outcompeted other carbon assimilators and dominated the SHP, presumably due to their ability to metabolize hydrogen and to withstand an anaerobic environment with fluctuating temperatures. Furthermore, most dominant microbes were capable of metabolizing inorganic sulfur-related compounds (abundant in SHP). However, Acidithiobacillus ferrooxidans was the only species among key rare microbes with the capability to fix nitrogen, suggesting a key role in nitrogen cycling. In addition to potential metabolic interactions, based on the 16S rRNAs gene sequence of Nanoarchaeum-related and its potential host Ignicoccus-related archaea, as well as sequences of viruses and CRISPR arrays, we inferred that there were complex microbe-microbe interactions. Conclusions: Our study provided evidence that there were numerous microbe-microbe and microbe-environment interactions within the microbial community in an acidic hot spring. We proposed that Hydrogenobaculum bacteria were the dominant microbial genus, as they were able to metabolize hydrogen, assimilate carbon and live in an anaerobic environment with fluctuating temperatures.