JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma

Chromosome 17q21-ter is commonly gained in neuroblastoma, but it is unclear which gene in the region is important for tumorigenesis. The JMJD6 gene at 17q21-ter activates gene transcription. Here we show that JMJD6 forms protein complexes with N-Myc and BRD4, and is important for E2F2, N-Myc and c-Myc transcription. Knocking down JMJD6 reduces neuroblastoma cell proliferation and survival in vitro and tumor progression in mice, and high levels of JMJD6 expression in human neuroblastoma tissues independently predict poor patient prognosis. In addition, JMJD6 gene is associated with transcriptional super-enhancers. Combination therapy with the CDK7/super-enhancer inhibitor THZ1 and the histone deacetylase inhibitor panobinostat synergistically reduces JMJD6, E2F2, N-Myc, c-Myc expression, induces apoptosis in vitro and leads to neuroblastoma tumor regression in mice, which are significantly reversed by forced JMJD6 over-expression. Our findings therefore identify JMJD6 as a neuroblastoma tumorigenesis factor, and the combination therapy as a treatment strategy

d-alpha Correlation functions and collective motion in Xe+Au collisions at E/A=50 MeV

The interplay of the effects of geometry and collective motion on d-$\alpha$ correlation functions is investigated for central Xe+Au collisions at E/A=50 MeV. The data cannot be explained without collective motion, which could be partly along the beam axis. A semi-quantitative description of the data can be obtained using a Monte-Carlo model, where thermal emission is superimposed on collective motion. Both the emission volume and the competition between the thermal and collective motion influence significantly the shape of the correlation function, motivating new strategies for extending intensity interferometry studies to massive particles.Comment: Accepted for publication on Physics Letters

Partial Wave Analysis of J/ψ→γ(K+K−π+π−)J/\psi \to \gamma (K^+K^-\pi^+\pi^-)

BES data on $J/\psi \to \gamma (K^+K^-\pi^+\pi^-)$ are presented. The $K^*\bar K^*$ contribution peaks strongly near threshold. It is fitted with a broad $0^{-+}$ resonance with mass $M = 1800 \pm 100$ MeV, width $\Gamma = 500 \pm 200$ MeV. A broad $2^{++}$ resonance peaking at 2020 MeV is also required with width $\sim 500$ MeV. There is further evidence for a $2^{-+}$ component peaking at 2.55 GeV. The non-$K^*\bar K^*$ contribution is close to phase space; it peaks at 2.6 GeV and is very different from $K^{*}\bar{K^{*}}$.Comment: 15 pages, 6 figures, 1 table, Submitted to PL

Fluorescent Labeling Agents Change Binding Profiles of Glycan-Binding Proteins

Interactions of glycan-binding proteins (GBPs) with glycans are essential in cell adhesion, bacterial/viral infection, and cellular signaling pathways. Experimental characterization of these interactions based on glycan microarrays typically involves (1) labeling GBPs directly with fluorescent reagents before incubation with the microarrays, or (2) labeling GBPs with biotin before the incubation and detecting the captured GBPs after the incubation using fluorescently labeled streptavidin, or (3) detecting the captured GBPs after the incubation using fluorescently labeled antibodies raised against the GBPs. The fluorescent signal is mostly measured ex situ after excess fluorescent materials are washed off. In this study by using a label-free optical scanner for glycan microarray detection, we measured binding curves of 7 plant lectins to 24 glycans: four β1-4-linked galactosides, three β1-3-linked galactosides, one β-linked galactoside, one α-linked N -acetylgalactosaminide, eight α2-3-linked sialosides, and seven α2-6-linked sialosides. From association and dissociation constants deduced by global-fitting the binding curves, we found that (1) labeling lectins directly with fluorescent agents change binding profiles of lectins, in some cases by orders of magnitude; (2) those lectin-glycan binding reactions characterized with large dissociation rates, though biologically relevant, are easily missed or deemed insignificant in ex situ fluorescence-based assays as most captured lectins are washed off before detection. This study highlights the importance of label-free real-time detection of protein-ligand interactions and the potential pitfall in interpreting fluorescence-based assays for characterization of protein-glycan interactions