Interactions between neurons and glial cells in the brain may serve important functions in the development, maintenance, and plasticity of neural circuits. Fast neuron-glia synaptic transmission has been found between hippocampal neurons and NG2 cells, a distinct population of macroglia-like cells widely distributed in the brain. We report that these neuron-glia synapses undergo activity-dependent modifications analogous to long-term potentiation (LTP) at excitatory synapses, a hallmark of neuronal plasticity. However, unlike the induction of LTP at many neuron-neuron synapses, both induction and expression of LTP at neuron-NG2 synapses involve Ca2+-permeable AMPA receptors on NG2 cells.

The RNA-dependent RNA polymerase (RdRp) from hepatitis C virus (HCV), nonstructural protein 5B (NS5B), has recently been shown to direct de novo initiation using a number of complex RNA templates. In this study, we analyzed the features in simple RNA templates that are required to direct de novo initiation of RNA synthesis by HCV NS5B. NS5B was found to protect RNA fragments of 8 to 10 nucleotides (nt) from RNase digestion. However, NS5B could not direct RNA synthesis unless the template contained a stable secondary structure and a single-stranded sequence that contained at least one 3 cytidylate. The structure of a 25-nt template, named SLD3, was determined by nuclear magnetic resonance spectroscopy to contain an 8-bp stem and a 6-nt single-stranded sequence. Systematic analysis of changes in SLD3 revealed which features in the stem, loop, and 3 single-stranded sequence were required for efficient RNA synthesis. Also, chimeric molecules composed of DNA and RNA demonstrated that a DNA molecule containing a 3-terminal ribocytidylate was able to direct RNA synthesis as efficiently as a sequence composed entirely of RNA. These results define the template sequence and structure sufficient to direct the de novo initiation of RNA synthesis by HCV RdRp.Hepatitis C virus (HCV), a plus-strand RNA virus, is estimated to infect up to 3% of the world's population (44), causing liver cirrhosis and hepatocellular carcinoma (14). Following entry into the infected cell, the viral RNA directs the translation of a polyprotein that is proteolytically processed to produce 10 individual structural and nonstructural proteins (15, 32). Nonstructural protein 5B (NS5B) is at the C terminus of the polyprotein. NS5B is an RNA-dependent RNA polymerase (RdRp). Based on the paradigms of other RNA virus replication strategies (8), NS5B, along with viral and cellular proteins, forms a replicase that replicates the HCV genome. At present, functional HCV replicase has not been demonstrated in vitro. Therefore, studies of HCV RNA synthesis have focused on recombinant NS5B.Recombinant HCV NS5B can catalyze a number of reactions. In the presence of a primer-template duplex, NS5B catalyzes template-dependent but relatively nonspecific RNA synthesis (5, 23-25, 45, 46). In addition, NS5B has recently been reported to direct de novo (oligonucleotide primer-independent) synthesis (26, 30, 47), a mechanism used for the replication of many plus-strand RNA viruses (8). De novo initiation of RNA synthesis may be especially relevant for HCV since, to our knowledge, it does not contain a VPg-like protein that could mediate protein-primed RNA synthesis, and there is no evidence for a cap-snatching mechanism (32). De novo RNA synthesis directed by HCV NS5B prefers a cytidylate template and the substrate nucleotide GTP (26, 42), although ATP can also be used as an initiation nucleotide (29,42,47). In general, RNA polymerases have a higher K m for the initiation nucleotide than for the same nucleotide during elongating RNA synthesis (for examples, see references ...

Abstract:Vascular anomalies are among the most common congenital and neonatal dysmorphogenesis, which are separated into hemangiomas and vascular malformations. They can occur in various areas throughout the body, with 60% being located in the head and neck. The true mechanism of pathogenesis of vascular anomalies is still unclear. Various treatment methods have been reported, and there are still controversies over the selection of different treatment modalities. Based on the clinical and basic research and current literature, the Chinese Division of Oral and Maxillofacial Vascular Anomalies formulated a treatment guideline for hemangiomas and vascular malformations of the head and neck, which will be modified and updated periodically based on new medical evidence and research.

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Objectives To improve margin revision, this study characterizes the number, fragmentation, and orientation of tumor bed margins (TBM) in patients with pT1-2 pN0 squamous cell carcinoma (SCC) of the oral tongue. Materials and Methods Pathology reports (n = 346) were reviewed. TBM parameters were indexed. In Group 1 patients all margins were obtained from the glossectomy specimen and there were no TBM. In Revision Group/Group 2 (n = 103), tumor bed was sampled to revise suboptimal margins identified by examination of the glossectomy specimen. In Group 3 (n = 124), TBM were obtained before examination of the glossectomy specimen. Results and Conclusions Fewer TBMs were obtained per patient in Group 2 compared to Group 3 (57/103, 55% of patients with < 3 vs. 117/124, 94%, ≥3 TBMs, respectively). The new margin surface was more frequently indicated in Group 2 compared to Group 3 (59/103, 57%, vs. 19/124, 15%, p < .001). If glossectomy specimen margins are accepted as the reference standard, then the TBM was 15% sensitive in Group 2 (95% confidence interval [CI], 7–29) and 32% sensitive in Group 3 (95% CI, 15–55). TBM fragmentation (23/103, 22% vs. 42/124, 34%) and frozen vs. permanent discrepancies (8/103, 3% vs. 3/124, 2%) were similar between Groups 2 and 3. The new margin surface was not indicated in 6 of 11 cases with discrepant frozen vs. permanent pathology findings, precluding judgment on final margin status. To facilitate the assessment of final margins, TBM should be represented by one tissue fragment with a marked new margin surface.

Background/Aim Nobiletin, a major polymethoxyflavones ( PMF s) from citri reticulatae pericarpium ( CRP ), can inhibit several forms of cancer proliferation. However, the effects of nobiletin on nasopharyngeal carcinoma ( NPC ) C666‐1 cells remain largely unknown. Materials and Methods Cell counting kit 8 ( CCK 8) assay was used to measure cell vitality. Flow cytometry was performed to measure the apoptosis rate. Quantitative real‐time polymerase chain reaction ( qRT ‐ PCR ) and Western blot analysis were applied to determine the expression of mRNA and protein, respectively. Results We showed that the proliferation rate of C666‐1 cells was inhibited and the apoptosis rate was raised after treating with nobiletin. Moreover, nobiletin inhibited the expression of poly( ADP ‐ribose)polymerase‐2 ( PARP ‐2), and the tumor suppression effect of nobiletin on C666‐1 is associated with PARP ‐2‐dependent pathway. Conclusion We demonstrated for the first time that nobiletin inhibited the growth of C666‐1 cells, which may be relative to its regulation on PARP ‐2/ SIRT 1/ AMPK signaling pathway. Our result implied that nobiletin may serve as a strategy to treat nasopharyngeal carcinoma.

Neurons of cranial sensory ganglia are derived from the neural crest and ectodermal placodes, but the mechanisms that control the relative contributions of each are not understood. Crest cells of the second branchial arch generate few facial ganglion neurons and no vestibuloacoustic ganglion neurons, but crest cells in other branchial arches generate many sensory neurons. Here we report that the facial ganglia of Hoxa2 mutant mice contain a large population of crest-derived neurons, suggesting that Hoxa2 normally represses the neurogenic potential of second arch crest cells. This may represent an anterior transformation of second arch neural crest cells toward a fate resembling that of first arch neural crest cells, which normally do not express Hoxa2 or any other Hox gene. We additionally found that overexpressing Hoxa2 in cultures of P19 embryonal carcinoma cells reduced the frequency of spontaneous neuronal differentiation, but only in the presence of cotransfected Pbx and Meis Hox cofactors. Finally, expression of Hoxa2 and the cofactors in chick neural crest cells populating the trigeminal ganglion also reduced the frequency of neurogenesis in the intact embryo. These data suggest an unanticipated role for Hox genes in controlling the neurogenic potential of at least some cranial neural crest cells.