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

Nebuliser therapy in the intensive care unit

The relationship between identity, lived experience, sexual practices and the language through which these are conveyed has been widely debated in sexuality literature. For example, ‘coming out’ has famously been conceptualised as a ‘speech act’ (Sedgwick 1990) and as a collective narrative (Plummer 1995), while a growing concern for individuals’ diverse identifications in relations to their sexual and gender practices has produced interesting research focusing on linguistic practices among LGBT-identified individuals (Leap 1995; Kulick 2000; Cameron and Kulick 2006; Farqhar 2000). While an explicit focus on language remains marginal to literature on sexualities (Kulick 2000), issue of language use and translation are seldom explicitly addressed in the growing literature on intersectionality. Yet intersectional perspectives ‘reject the separability of analytical and identity categories’ (McCall 2005:1771), and therefore have an implicit stake in the ‘vernacular’ language of the researched, in the ‘scientific’ language of the researcher and in the relationship of continuity between the two. Drawing on literature within gay and lesbian/queer studies and cross-cultural studies, this chapter revisits debates on sexuality, language and intersectionality. I argue for the importance of giving careful consideration to the language we choose to use as researchers to collectively define the people whose experiences we try to capture. I also propose that language itself can be investigated as a productive way to foreground how individual and collective identifications are discursively constructed, and to unpack the diversity of lived experience. I address intersectional complexity as a methodological issue, where methodology is understood not only as the methods and practicalities of doing research, but more broadly as ‘a coherent set of ideas about the philosophy, methods and data that underlie the research process and the production of knowledge’ (McCall 2005:1774). My points are illustrated with examples drawn from my ethnographic study on ‘lesbian’ identity in urban Russia, interspersed with insights from existing literature. In particular, I aim to show that an explicit focus on language can be a productive way to explore the intersections between the global, the national and the local in cross-cultural research on sexuality, while also addressing issues of positionality and accountability to the communities researched

Migration-promoting role of VEGF-C and VEGF-C binding receptors in human breast cancer cells

Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic factor over-expressed in highly metastatic, cyclooxygenase (COX)-2 expressing breast cancer cells. We tested the hypothesis that tumour-derived VEGF-C may play an autocrine role in metastasis by promoting cellular motility through one or more VEGF-C-binding receptors VEGFR-2, VEGFR-3, neuropilin (NRP)-1, NRP-2, and integrin α9β1. We investigated the expression of these receptors in several breast cancer cell lines (MDA-MB-231, Hs578T, SK-BR-3, T-47D, and MCF7) and their possible requirement in migration of two VEGF-C-secreting, highly metastatic lines MDA-MB-231 and Hs578T. While cell lines varied significantly in their expression of above VEGF-C receptors, migratory activity of MDA-MB-231 and Hs578T cells was linked to one or more of these receptors. Depletion of endogenous VEGF-C by treatments with a neutralising antibody, VEGF-C siRNA or inhibitors of Src, EGFR/Her2/neu and p38 MAP kinases which inhibited VEGF-C production, inhibited cellular migration, indicating the requirement of VEGF-C for migratory function. Migration was differentially attenuated by blocking or downregulation of different VEGF-C receptors, for example treatment with a VEGFR-2 tyrosine kinase inhibitor, NRP-1 and NRP-2 siRNA or α9β1 integrin antibody, indicating the participation of one or more of the receptors in cell motility. This novel role of tumour-derived VEGF-C indicates that breast cancer metastasis can be promoted by coordinated stimulation of lymphangiogenesis and enhanced migratory activity of breast cancer cells

Role of Portal Vein Embolization in Hepatocellular Carcinoma Management and Its Effect on Recurrence: A Case-control Study

Background Liver regeneration that occurs after portal vein embolization (PVE) may have adverse effects on the microscopic tumor foci in the residual liver mass in patients with hepatocellular carcinoma (HCC). Methods Fifty-four HCC patients with inadequate functional residual liver volume were offered PVE during a seven-year period. Among them, 34 (63%) patients underwent curative resection. They were compared with a matched control group (n = 102) who underwent surgery without PVE. Postoperative complications, pattern of recurrence, and survival were compared between groups. Results In the PVE group, a pre-embolization functional residual liver volume of 23% (12-33.5%) improved to 34% (20-54%) (p = 0.005) at the time of surgery. When the two groups were compared, minor (PVE, 24%; control, 29%; p = 0.651) and major (PVE, 18%; control, 15%; p = 0.784) complications were similar. After a follow-up period of 35 months (standard deviation 25 months), extrahepatic recurrences were detected in 10 PVE patients (29%) and 41 control patients (40%) (p = 0.310). Intrahepatic recurrences were seen in 10 (29%) and 47 (46%) cases (p = 0.109) in the PVE and control groups, respectively. In the PVE group, 41% (n = 14) of the recurrences were detected before one year, compared with 42% (n = 43) in the control group (p = 1). Disease-free survival rates at 1, 3, and 5 years were 57, 29, and 26% in the control group and 60, 42, and 42% in the PVE group (log-rank, p = 0.335). On multivariate analysis, PVE was not a factor affecting survival (p = 0.821). Conclusions Portal vein embolization increases the resectability of initially unresectable HCC due to inadequate functional residual liver volume, and it has no deleterious oncological effect after major resection of HCC. © The Author(s) 2012.published_or_final_versionSpringer Open Choice, 28 May 201

Sporadic Colorectal Cancer Development Shows Rejuvenescence Regarding Epithelial Proliferation and Apoptosis

Background and Aims: Sporadic colorectal cancer (CRC) development is a sequential process showing age-dependency, uncontrolled epithelial proliferation and decreased apoptosis. During juvenile growth cellular proliferation and apoptosis are well balanced, which may be perturbed upon aging. Our aim was to correlate proliferative and apoptotic activities in aging human colonic epithelium and colorectal cancer. We also tested the underlying molecular biology concerning the proliferation- and apoptosis-regulating gene expression alterations. Materials and Methods: Colorectal biopsies from healthy children (n1 = 14), healthy adults (n2 = 10), adult adenomas (n3 = 10) and CRCs (n4 = 10) in adults were tested for Ki-67 immunohistochemistry and TUNEL apoptosis assay. Mitosis- and apoptosis-related gene expression was also studied in healthy children (n1 = 6), adult (n2 = 41) samples and in CRC (n3 = 34) in HGU133plus2.0 microarray platform. Measured alterations were confirmed with RT-PCR both on dependent and independent sample sets (n1=6, n2=6, n3 = 6). Results: Mitotic index (MI) was significantly higher (p,0.05) in intact juvenile (MI = 0.3360.06) and CRC samples (MI = 0.4260.10) compared to healthy adult samples (MI = 0.1560.06). In contrast, apoptotic index (AI) was decreased in children (0.1360.06) and significantly lower in cancer (0.0660.03) compared to healthy adult samples (0.1760.05). Eight proliferation- (e.g. MKI67, CCNE1) and 11 apoptosis-associated genes (e.g. TNFSF10, IFI6) had altered mRNA expression both in the course of normal aging and carcinogenesis, mainly inducing proliferation and reducing apoptosis compared to healthy adults. Eight proliferation-associated genes including CCND1, CDK1, CDK6 and 26 apoptosis-regulating genes (e.g. SOCS3) were differently expressed between juvenile and cancer groups mostly supporting the pronounced cell growth in CRC. Conclusion: Colorectal samples from children and CRC patients can be characterized by similarly increased proliferative and decreased apoptotic activities compared to healthy colonic samples from adults. Therefore, cell kinetic alterations during colorectal cancer development show uncontrolled rejuvenescence as opposed to the controlled cell growth in juvenile colonic epithelium

Search for an invisible muon philic scalar X0X_{0} or vector X1X_{1} via J/ψ→μ+μ−+invisibleJ/\psi\to\mu^+\mu^-+\rm{invisible} decay at BESIII

A light scalar $X_{0}$ or vector $X_{1}$ particles have been introduced as a possible explanation for the $(g-2)_{\mu}$ anomaly and dark matter phenomena. Using $(8.998\pm 0.039)\times10^9$ \jpsi events collected by the BESIII detector, we search for a light muon philic scalar $X_{0}$ or vector $X_{1}$ in the processes $J/\psi\to\mu^+\mu^- X_{0,1}$ with $X_{0,1}$ invisible decays. No obvious signal is found, and the upper limits on the coupling $g_{0,1}'$ between the muon and the $X_{0,1}$ particles are set to be between $1.1\times10^{-3}$ and $1.0\times10^{-2}$ for the $X_{0,1}$ mass in the range of $1<M(X_{0,1})<1000$~MeV$/c^2$ at 90$\%$ confidence level.Comment: 9 pages 7 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

First Observation of a Three-Resonance Structure in e+e−→e^+e^-\rightarrow{non-open} Charm Hadrons

We report the measurement of the cross sections for $e^+e^-$$\rightarrow${nOCH} (nOCH stands for non-open charm hadrons) with improved precision at center-of-mass energies from 3.645 to 3.871 GeV. We observe for the first time a three-resonance structure in the energy-dependent lineshape of the cross sections, which are $\mathcal R(3760)$, $\mathcal R(3780)$ and $\mathcal R(3810)$ with significances of $9.4\sigma$, $15.7\sigma$, and $9.8\sigma$, respectively. The $\mathcal R(3810)$ is observed for the first time. We found two solutions in analysis of the cross sections. For solution I [solution II], we measure the mass, the total width and the product of electronic width and nOCH decay branching fraction to be $(3805.8 \pm 1.1 \pm 2.7)$ [$(3805.8 \pm 1.1 \pm 2.7)$] MeV/$c^2$, $(11.6 \pm 2.6 \pm 1.9)$ [$(11.5 \pm 2.5 \pm 1.8)$] MeV, and $(10.8\pm 3.2\pm 2.3)$ [$(11.0\pm 2.9\pm 2.4)$] eV for the $\mathcal R(3810)$, respectively. In addition, we measure the branching fractions ${\mathcal B}({\mathcal R}(3760)$$\rightarrow${nOCH}$)=(24.5 \pm 13.4 \pm 27.4)\% [(6.8 \pm 5.4 \pm 7.6)\%]$ for the first time, and ${\mathcal B}(\mathcal R(3780)$$\rightarrow${nOCH}$)=(11.6 \pm 5.8 \pm 7.8)\% [(10.3 \pm 4.5 \pm 6.9)\%]$. Moreover, we determine the open-charm (OC) branching fraction ${\mathcal B}({\mathcal R}$$(3760)\rightarrow${OC}$)=(75.5 \pm 13.4 \pm 27.4)\% [(93.2 \pm 5.4 \pm 7.6)\%]$, which supports the interpretation of $\mathcal R(3760)$ as an OC pair molecular state, but contained a simple four-quark state component. The first uncertainties are from fits to the cross sections, and the second are systematic

Study of the doubly Cabibbo-suppressed decays Ds+→K+K+π−D^+_s\to K^+K^+\pi^- and Ds+→K+K+π−π0D^+_s\to K^+K^+\pi^-\pi^0

Based on 7.33 fb$^{-1}$ of $e^+e^-$ collision data collected at center-of-mass energies between 4.128 and 4.226 GeV with the BESIII detector, the experimental studies of the doubly Cabibbo-suppressed decays $D^+_s\to K^+K^+\pi^-$ and $D^+_s\to K^+K^+\pi^-\pi^0$ are reported. We determine the absolute branching fraction of $D^+_s\to K^+K^+\pi^-$ to be (${1.23^{+0.28}_{-0.25}}({\rm stat})\pm0.06({\rm syst})$) $\times 10^{-4}$. No significant signal of $D^+_s\to K^+K^+\pi^-\pi^0$ is observed and the upper limit on its decay branching fraction at 90\% confidence level is set to be $1.7\times10^{-4}$.Comment: 10 pages, 4 figures, 4 table

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