A viral microRNA functions as an orthologue of cellular miR-155

All metazoan eukaryotes express microRNAs (miRNAs), roughly 22-nucleotide regulatory RNAs that can repress the expression of messenger RNAs bearing complementary sequences. Several DNA viruses also express miRNAs in infected cells, suggesting a role in viral replication and pathogenesis. Although specific viral miRNAs have been shown to autoregulate viral mRNAs or downregulate cellular mRNAs, the function of most viral miRNAs remains unknown. Here we report that the miR-K12-11 miRNA encoded by Kaposi's-sarcoma-associated herpes virus (KSHV) shows significant homology to cellular miR-155, including the entire miRNA 'seed' region. Using a range of assays, we show that expression of physiological levels of miR-K12-11 or miR-155 results in the downregulation of an extensive set of common mRNA targets, including genes with known roles in cell growth regulation. Our findings indicate that viral miR-K12-11 functions as an orthologue of cellular miR-155 and probably evolved to exploit a pre-existing gene regulatory pathway in B cells. Moreover, the known aetiological role of miR-155 in B-cell transformation suggests that miR-K12-11 may contribute to the induction of KSHV-positive B-cell tumours in infected patients.     

Isotope-induced partial localization of core electrons in the homonuclear molecule N2

Because of inversion symmetry and particle exchange, all constituents of homonuclear diatomic molecules are in a quantum mechanically non-local coherent state; this includes the nuclei and deep-lying core electrons. Hence, the molecular photoemission can be regarded as a natural double-slit experiment: coherent electron emission originates from two identical sites, and should give rise to characteristic interference patterns. However, the quantum coherence is obscured if the two possible symmetry states of the electronic wavefunction ('gerade' and 'ungerade') are degenerate; the sum of the two exactly resembles the distinguishable, incoherent emission from two localized core sites. Here we observe the coherence of core electrons in N(2) through a direct measurement of the interference exhibited in their emission. We also explore the gradual transition to a symmetry-broken system of localized electrons by comparing different isotope-substituted species--a phenomenon analogous to the acquisition of partial 'which-way' information in macroscopic double-slit experiments.     

HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers

DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n?=?19), diploid (n?=?31), and aneuploid (n?=?47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers.     

Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin

Gerodermia osteodysplastica is an autosomal recessive disorder characterized by wrinkly skin and osteoporosis. Here we demonstrate that gerodermia osteodysplastica is caused by loss-of-function mutations in SCYL1BP1, which is highly expressed in skin and osteoblasts. The protein localizes to the Golgi apparatus and interacts with Rab6, identifying SCYL1BP1 as a golgin. These results associate abnormalities of the secretory pathway with age-related changes in connective tissues.     

Light-dependent phosphorylation of Bardet–Biedl syndrome 5 in photoreceptor cells modulates its interaction with arrestin1

Arrestins are dynamic proteins that move between cell compartments triggered by stimulation of G-protein-coupled receptors. Even more dynamically in vertebrate photoreceptors, arrestin1 (Arr1) moves between the inner and outer segments according to the light conditions. Previous studies have shown that the light-driven translocation of Arr1 in rod photoreceptors is initiated by rhodopsin through a phospholipase C/protein kinase C (PKC) signaling cascade. The purpose of this study is to identify the PKC substrate that regulates the translocation of Arr1. Mass spectrometry was used to identify the primary phosphorylated proteins in extracts prepared from PKC-stimulated mouse eye cups, confirming the finding with in vitro phosphorylation assays. Our results show that Bardet–Biedl syndrome 5 (BBS5) is the principal protein phosphorylated either by phorbol ester stimulation or by light stimulation of PKC. Via immunoprecipitation of BBS5 in rod outer segments, Arr1 was pulled down; phosphorylation of BBS5 reduced this co-precipitation of Arr1. Immunofluorescence and immunoelectron microscopy showed that BBS5 principally localizes along the axonemes of rods and cones, but also in photoreceptor inner segments, and synaptic regions. Our principal findings in this study are threefold. First, we demonstrate that BBS5 is post-translationally regulated by phosphorylation via PKC, an event that is triggered by light in photoreceptor cells. Second, we find a direct interaction between BBS5 and Arr1, an interaction that is modulated by phosphorylation of BBS5. Finally, we show that BBS5 is distributed along the photoreceptor axoneme, co-localizing with Arr1 in the dark. These findings suggest a role for BBS5 in regulating light-dependent translocation of Arr1 and a model describing its role in Arr1 translocation is proposed.     

量子概率论与无穷维分析：从基础到应用

2003年春季学期德国Greifswald大学举办了一系列以“量子概率论：从基础到应用”为主题的学术活动，其中包括一个春季学习班、两个工作会议以及于6月22—28日举行的“量子概率论与无穷维分析”国际会议。同年秋季作为该活动的延续又在意大利Levico Terme举行了一期“量子独立增量过程”的工作会议。[第一段]     

Expression of a fusion protein of human ciliary neurotrophic factor and soluble CNTF-receptor and identification of its activity

Ciliary neurotrophic factor (CNTF) has pleiotropic actions on many neuronal populations as well as on glia. Signal transduction by CNTF requires that it bind first to CNTF-R, permitting the recruitment of gpl30 and LIF-R, forming a tripartite receptor complex. Ceils that only express gpl30 and LIF-R, but not CNTF-R are refractory to stimulation by CNTF. On many target ceils CNTF only acts in the presence of its specific agonistic soluble receptors. We engineered a soluble fusion protein by linking the COOH-terminus of sCNTF-R to the NH2-terminus of CNTF. Recombinant CNTF/sCNTF-R fusion protein (Hyper-CNTF) was sac-cessfully expressed in COS-7 cells. The apparent molecular mass of the Hyper-CNTF protein was estimated from western blots to be 75 kDa. Proliferation assays of tmnsfected BAF/3 cells in response to CNTF and Hy-per-CNTF were used to verify the activity of the cytokines. The proliferative results confirmed that CNTF required homodimerization of the gpl30, CNTF-R and LIF-R receptor subunlt whereas Hyper-CNTF required heterodimerization of the gpl30 and LIF-R receptor subunit. We concluded that the fusion protein Hyper-CNTF had superagonistic activity on target cells expressing gpl30 and LIF-R, but lacking membrane-beund CNTF-R.