A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Gene Expression Profiling of Liver Cancer Stem Cells by RNA-Sequencing

Background: Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90 + liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90 + cells sorted from tumor (CD90 +CSCs) with parallel non-tumorous liver tissues (CD90 +NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis. Methodology/Principal Findings: CD90 + cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90 + cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90 +CSCs and CD90 +NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90 +CSCs and CD90 +NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90 +CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90 +CSCs compared to CD90 +NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90 +CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90 +CSCs in liver tumor tissues. Conclusions/Significance: The identified genes, such as GPC3 that are distinctly expressed in liver CD90 +CSCs, may be promising gene candidates for HCC therapy without inducing damages to normal liver stem cells. © 2012 Ho et al.published_or_final_versio

FTY720 Suppresses Liver Tumor Metastasis by Reducing the Population of Circulating Endothelial Progenitor Cells

Background: Surgical procedures such as liver resection and liver transplantation are the first-line treatments for hepatocellular carcinoma (HCC) patients. However, the high incidence of tumor recurrence and metastasis after liver surgery remains a major problem. Recent studies have shown that hepatic ischemia-reperfusion (I/R) injury and endothelial progenitor cells (EPCs) contribute to tumor growth and metastasis. We aim to investigate the mechanism of FTY720, which was originally applied as an immunomodulator, on suppression of liver tumor metastasis after liver resection and partial hepatic I/R injury. Methodology/Principal Findings: An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Two weeks after orthotopic liver tumor implantation, the rats underwent liver resection for tumor-bearing lobe and partial hepatic I/R injury. FTY720 (2 mg/kg) was administered through the inferior caval vein before and after I/R injury. Blood samples were taken at days 0, 1, 3, 7, 14, 21 and 28 for detection of circulating EPCs (CD133+CD34+). Our results showed that intrahepatic and lung metastases were significantly inhibited together with less tumor angiogenesis by FTY720 treatment. The number of circulating EPCs was also significantly decreased by FTY720 treatment from day 7 to day 28. Hepatic gene expressions of CXCL10, VEGF, CXCR3, CXCR4 induced by hepatic I/R injury were down-regulated in the treatment group. Conclusions/Significance: FTY720 suppressed liver tumor metastasis after liver resection marred by hepatic I/R injury in a rat liver tumor model by attenuating hepatic I/R injury and reducing circulating EPCs. © 2012 Li et al.published_or_final_versio

Search for an axion-like particle in J/ψJ/\psi radiative decays

We search for an axion-like particle (ALP) $a$ through the process $\psi(3686)\rightarrow\pi^+\pi^-J/\psi$, $J/\psi\rightarrow\gamma a$, $a\rightarrow\gamma\gamma$ in a data sample with $(2708.1\pm14.5)\times10^6$ $\psi(3686)$ events collected by the BESIII detector. No significant ALP signal is observed over the expected background, and the upper limits on the branching fraction of the decay $J/\psi\rightarrow\gamma a$ and the ALP-photon coupling constant $g_{a\gamma\gamma}$ are set at the 95\% confidence level in the mass range of 0.165\leq m_a\leq2.84\,\mbox{GeV}/c^2. The limits on $\mathcal{B}(J/\psi\rightarrow\gamma a)$ range from $8.3\times10^{-8}$ to $1.8\times10^{-6}$ over the search region, and the constraints on the ALP-photon coupling are the most stringent to date for 0.165\leq m_a\leq1.468\,\mbox{GeV}/c^2.Comment: 10 pages, 5 figure

Production of doubly-charged Δ\Delta baryon in e+e−e^{+}e^{-} annihilation at energies from 2.3094 to 2.6464 GeV

The processes $e^{+}e^{-} \to \Delta^{++}\bar{\Delta}^{--}$ and $e^{+}e^{-}\to \Delta^{++} \bar{p} \pi^{-} + c.c.$ are studied for the first time with $179~{\rm pb}^{-1}$ of $e^{+}e^{-}$ annihilation data collected with the BESIII detector at center-of-mass energies from $2.3094$ GeV to $2.6464$ GeV. No significant signal for the $e^{+}e^{-}\to \Delta^{++}\bar{\Delta}^{--}$ process is observed and the upper limit of the Born cross section is estimated at each energy point. For the process $e^{+}e^{-} \to \Delta^{++} \bar{p} \pi^{-} + c.c.$, a significant signal is observed at center-of-mass energies near 2.6454 GeV and the corresponding Born cross section is reported.Comment: 10 pages, 4 figure

Measurements of the branching fractions of the inclusive decays D0(D+)→π+π+π−X

Using eþe− annihilation data corresponding to an integrated luminosity of 2.93 fb−1 taken at a center-of mass energy of 3.773 GeV with the BESIII detector, we report the first measurements of the branching fractions of the inclusive decays D0 → πþπþπ−X and Dþ → πþπþπ−X, where pions from K0 S decays have been excluded from the πþπþπ− system and X denotes any possible particle combination. The branching fractions of D0ðDþÞ → πþπþπ−X are determined to be BðD0 → πþπþπ−XÞ¼ð17.60 0.11 0.22Þ% and BðDþ → πþπþπ−XÞ¼ð15.25 0.09 0.18Þ%, where the first uncertainties are statistical and the second systematic

Measurements of the electric and magnetic form factors of the neutron for time-like momentum transfer

We present the first measurements of the electric and magnetic form factors of the neutron in the time-like (positive $q^2$) region as function of four-momentum transfer. We explored the differential cross sections of the reaction $e^+e^- \rightarrow \bar{n}n$ with data collected with the BESIII detector at the BEPCII accelerator, corresponding to an integrated luminosity of 354.6 pb$^{-1}$ in total at twelve center-of-mass energies between $\sqrt{s} = 2.0 - 2.95$ GeV. A relative uncertainty of 18% and 12% for the electric and magnetic form factors, respectively, is achieved at $\sqrt{s} = 2.3935$ GeV. Our results are comparable in accuracy to those from electron scattering in the comparable space-like (negative $q^2$) region of four-momentum transfer. The electromagnetic form factor ratio $R_{\rm em}\equiv |G_E|/|G_M|$ is within the uncertainties close to unity. We compare our result on $|G_E|$ and $|G_M|$ to recent model predictions, and the measurements in the space-like region to test the analyticity of electromagnetic form factors.Comment: main paper: 9 pages, 6 figures, 3 tables; supplement: 9 pages, 28 table

Measurement of the C ⁣PC\!P-even fraction of D0→K+K−π+π−D^0\to K^+K^-\pi^+\pi^-

A determination of the $C\!P$-even fraction $F_+$ in the decay $D^0 \to K^+K^-\pi^+\pi^-$ is presented. Using $2.93$ fb$^{-1}$ of $e^+e^-\to\psi(3770)\to D\bar{D}$ data collected by the BESIII detector, one charm meson is reconstructed in the signal mode and the other in a $C\!P$ eigenstate or the decay $D\to K_{S, L}^0\pi^+\pi^-$. Analysis of the relative rates of these double-tagged events yields the result $F_+ = 0.730 \pm 0.037 \pm 0.021$, where the first uncertainty is statistical and the second is systematic. This is the first model-independent measurement of $F_+$ in $D^0 \to K^+K^-\pi^+\pi^-$ decays.Comment: 13 pages, 5 figure