Epigenetic inactivation of the miR-34a in hematological malignancies

miR-34a is a transcriptional target of p53 and implicated in carcinogenesis. We studied the role of miR-34a methylation in a panel of hematological malignancies including acute leukemia [acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)], chronic leukemia [chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)], multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). The methylation status of miR-34a promoter was studied in 12 cell lines and 188 diagnostic samples by methylation-specific polymerase chain reaction. miR-34a promoter was unmethylated in normal controls but methylated in 75% lymphoma and 37% myeloma cell lines. Hypomethylating treatment led to re-expression of pri-miR-34a transcript in lymphoma cells with homozygous miR-34a methylation. In primary samples at diagnosis, miR-34a methylation was detected in 4% CLL, 5.5% MM samples and 18.8% of NHL at diagnosis but none of ALL, AML and CML (P = 0.011). In MM patients with paired samples, miR-34a methylation status remained unchanged at progression. Amongst lymphoid malignancies, miR-34a was preferentially methylated in NHL (P = 0.018), in particular natural killer (NK)/T-cell lymphoma. In conclusion, amongst hematological malignancies, miR-34a methylation is preferentially hypermethylated in NHL, in particular NK/T-cell lymphoma, in a tumor-specific manner, therefore the role of miR-34a in lymphomagenesis warrants further study. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

Cytomolecular identification of individual wheat-wheat chromosome arm associations in wheat-rye hybrids

Chromosome pairing in the meiotic metaphase I of wheatrye hybrids has been characterized by sequential genomic and fluorescent in situ hybridization allowing not only the discrimination of wheat and rye chromosomes, but also the identification of the individual wheat and rye chromosome arms involved in the chromosome associations. The majority of associations (93.8%) were observed between the wheat chromosomes. The largest number of wheat-wheat chromosome associations (53%) was detected between the A and D genomes, while the frequency of B-D and A-B associations was significantly lower (32 and 8%, respectively). Among the A-D chromosome associations, pairing between the 3AL and 3DL arms was observed with the highest frequency, while the most frequent of all the chromosome associations (0.113/ cell) was found to be the 3DS-3BS. Differences in the pairing frequency of the individual chromosome arms of wheat-rye hybrids have been discussed in relation to the homoeologous relationships between the constituent genomes of hexaploid wheat

Developmental changes in the role of different metalinguistic awareness skills in Chinese reading acquisition from preschool to third grade

Copyright @ 2014 Wei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The present study investigated the relationship between Chinese reading skills and metalinguistic awareness skills such as phonological, morphological, and orthographic awareness for 101 Preschool, 94 Grade-1, 98 Grade-2, and 98 Grade-3 children from two primary schools in Mainland China. The aim of the study was to examine how each of these metalinguistic awareness skills would exert their influence on the success of reading in Chinese with age. The results showed that all three metalinguistic awareness skills significantly predicted reading success. It further revealed that orthographic awareness played a dominant role in the early stages of reading acquisition, and its influence decreased with age, while the opposite was true for the contribution of morphological awareness. The results were in stark contrast with studies in English, where phonological awareness is typically shown as the single most potent metalinguistic awareness factor in literacy acquisition. In order to account for the current data, a three-stage model of reading acquisition in Chinese is discussed.National Natural Science Foundation of China and Knowledge Innovation Program of the Chinese Academy of Sciences

Transmission and pathogenicity of novel reassortants derived from Eurasian avian-like and 2009 pandemic H1N1 influenza viruses in mice and guinea pigs

Given the present extensive co-circulation in pigs of Eurasian avian-like (EA) swine H1N1 and 2009 pandemic (pdm/09) H1N1 viruses, reassortment between them is highly plausible but largely uncharacterized. Here, experimentally co-infected pigs with a representative EA virus and a pdm/09 virus yielded 55 novel reassortant viruses that could be categorized into 17 genotypes from Gt1 to Gt17 based on segment segregation. Majority of novel reassortants were isolated from the lower respiratory tract. Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs. The most transmissible reassortant genotypes demonstrated in guinea pigs (Gt2, Gt3, Gt7, Gt10 and Gt13) were also the most lethal in mice. Notably, nearly all these highly virulent reassortants (all except Gt13) were characterized with possession of EA H1 and full complement of pdm/09 ribonucleoprotein genes. Compositionally, we demonstrated that EA H1-222G contributed to virulence by its ability to bind avian-type sialic acid receptors, and that pdm/09 RNP conferred the most robust polymerase activity to reassortants. The present study revealed high reassortment compatibility between EA and pdm/09 viruses in pigs, which could give rise to progeny reassortant viruses with enhanced virulence and transmissibility in mice and guinea pig models

Downgrading MELD Improves the Outcomes after Liver Transplantation in Patients with Acute-on-Chronic Hepatitis B Liver Failure

Background: High score of model for end-stage liver diseases (MELD) before liver transplantation (LT) indicates poor prognosis. Artificial liver support system (ALSS) has been proved to effectively improve liver and kidney functions, and thus reduce the MELD score. We aim to evaluate whether downgrading MELD score could improve patient survival after LT. Methodology/Principal Findings: One hundred and twenty-six LT candidates with acute-on-chronic hepatitis B liver failure and MELD score $30 were included in this prospective study. Of the 126 patients, 42 received emergency LT within 72 h (ELT group) and the other 84 were given ALSS as salvage treatment. Of the 84 patients, 33 were found to have reduced MELD score (,30) on the day of LT (DGM group), 51 underwent LT with persistent high MELD score (N-DGM group). The median waiting time for a donor was 10 for DGM group and 9.5 days for N-DGM group. In N-DGM group there is a significantly higher overall mortality (43.1$30 was effective i

Preference of Small Molecules for Local Minimum Conformations when Binding to Proteins

It is well known that small molecules (ligands) do not necessarily adopt their lowest potential energy conformations when binding to proteins. Analyses of protein-bound ligand crystal structures have reportedly shown that many of them do not even adopt the conformations at local minima of their potential energy surfaces (local minimum conformations). The results of these analyses raise a concern regarding the validity of virtual screening methods that use ligands in local minimum conformations. Here we report a normal-mode-analysis (NMA) study of 100 crystal structures of protein-bound ligands. Our data show that the energy minimization of a ligand alone does not automatically stop at a local minimum conformation if the minimum of the potential energy surface is shallow, thus leading to the folding of the ligand. Furthermore, our data show that all 100 ligand conformations in their protein-bound ligand crystal structures are nearly identical to their local minimum conformations obtained from NMA-monitored energy minimization, suggesting that ligands prefer to adopt local minimum conformations when binding to proteins. These results both support virtual screening methods that use ligands in local minimum conformations and caution about possible adverse effect of excessive energy minimization when generating a database of ligand conformations for virtual screening

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721