Poliovirus Infection Transiently Increases CopII Vesicle Budding

Poliovirus (PV) requires membranes of the host cell\u27s secretory pathway to generate replication complexes (RCs) for viral RNA synthesis. Recent work identified the intermediate compartment and the Golgi apparatus as the precursors of the replication organelles of PV (N. Y. Hsu et al., Cell 141:799-811, 2010). In this study, we examined the effect of PV on COPII vesicles, the secretory cargo carriers that bud from the endoplasmic reticulum and homotypically fuse to form the intermediate compartment that matures into the Golgi apparatus. We found that infection by PV results in a biphasic change in functional COPII vesicle biogenesis in cells, with an early enhancement and subsequent inhibition. Concomitant with the early increase in COPII vesicle formation, we found an increase in the membrane fraction of Sec16A, a key regulator of COPII vesicle formation. We suggest that the early burst in COPII vesicle formation detected benefits PV by increasing the precursor pool required for the formation of its RCs

Decreasing Herpes Simplex Viral Infectivity in Solution by Surface-Immobilized and Suspended N,N-Dodecyl,methyl-polyethylenimine

Purpose To explore surface-immobilized and suspended modalities of the hydrophobic polycation N,N-dodecyl,methyl-polyethylenimine (DMPEI) for the ability to reduce viral infectivity in aqueous solutions containing herpes simplex viruses (HSVs) 1 and 2. Methods Surface-immobilized (coated onto surfaces) and suspended DMPEI were incubated with aqueous solutions containing HSV-1 or -2 to measure the antiviral effect of the hydrophobic polycation’s formulations on HSVs. Results DMPEI coated on either polyethylene slides or male latex condoms dramatically decreases infectivity in solutions containing HSV-1 or -2. Moreover, DMPEI suspended in aqueous solution markedly reduces the infectious titer of these HSVs. Conclusion Our results suggest potential uses of DMPEI for both prophylaxis (in the form of coated condoms) and treatment (as a topical suspension) for HSV infections.Martin Family Graduate FellowshipNational Institutes of Health (U.S.) (Grant AI057552)United States. Army Research Office (Grant W911NF-07-D-0004

Fabrication of double-ceramic-layer TBCs by suspension plasma spray

Rare-earth zirconates, such as La2Zr2O7 and Gd2Zr2O7, have been investigated as one of the candidates for replacing conventional yttria-stabilized zirconia (YSZ) for thermal barrier coating (TBC) applications at higher turbine inlet temperatures. Rare-earth zirconate oxides exhibit little phase transformation upon heating up to melting temperature as well as low thermal conductivity, where as their mechanical properties is inferior to those of YSZ TBCs. Double-ceramic-layer (DCL) TBCs have been investigated in order to take advantage of beneficial characteristics of both YSZ and rare-earth zirconate. In this study, the fabrication of DCL-TBCs with YSZ layer and rare-earth-zirconate top layer by using suspension plasma spray are reported. Microstructure, compositional profile, thermal conductivity, and thermal durability of DCL-TBCs are characterized. The usefulness of these DCL-TBCs is also discussed

Synthesis of a 6-Methyl-7-Deaza Analogue of Adenosine that Potently Inhibits Replication of Polio and Dengue Viruses

Bioisosteric deaza analogues of 6-methyl-9-β-D-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-β-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC50 = 11 nM) and dengue virus (DENV) in Vero cells (IC50 = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was >100-fold after incubation for 7 h. Mechanistic studies of the 5'-triphosphate of 7-deaza-6-methyl-9-β-D-ribofuranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP

Optical Coherence Tomographic Finding in a Case of Macular Coloboma

PURPOSE: To report the optical coherence tomography (OCT) findings in a patient with unilateral macular coloboma. METHODS: A 12-year-old male was presented with macular coloboma in the left eye. The optical coherence tomography was performed with fluorescein angiography (FA). RESULTS: The OCT revealed the crater-like depression in the macula, demonstrating atrophic neurosensory retina, and an absence of retinal pigment epithelium and choroid in the lesion. FA showed hypofluorescence corresponding to the size of the lesion in both early and late frames without leakage of dye at any stage. CONCLUSIONS: The OCT can be beneficial to confirm the diagnosis of macular coloboma

Facial reanimation with masseter nerve–innervated free gracilis muscle transfer in established facial palsy patients

Background The masseter nerve is a useful donor nerve for reconstruction in patients with established facial palsy, with numerous advantages including low morbidity, a strong motor impulse, high reliability, and fast reinnervation. In this study, we assessed the results of masseter nerve–innervated free gracilis muscle transfer in established facial palsy patients. Methods Ten patients with facial palsy who received treatment from January 2015 to January 2017 were enrolled in this study. Three patients received masseter nerve–only free gracilis transfer, and seven received double-innervated free gracilis transfer (masseter nerve and a cross-face nerve graft). Patients were evaluated using the Facial Assessment by Computer Evaluation software (FACEgram) to quantify oral commissure excursion and symmetry at rest and when smiling after muscle transfer. Results The mean time between surgery and initial movement was roughly 167.7 days. A statistically significant increase in excursion at rest and when smiling was seen after muscle transfer. There was a significant increase in the distance of oral commissure excursion at rest and when smiling. A statistically significant increase was observed in symmetry when smiling. Terzis’ functional and aesthetic grading scores showed significant improvements postoperatively. Conclusions Masseter nerve innervation is a good option with many uses in in established facial palsy patients. For some conditions, it is the first-line treatment. Free gracilis muscle transfer using the masseter nerve has excellent results with good symmetry and an effective degree of recovery

A Targeted RNA Interference Screen Reveals Novel Epigenetic Factors That Regulate Herpesviral Gene Expression

ABSTRACT Herpes simplex virus (HSV) utilizes and subverts host chromatin mechanisms to express its lytic gene products in mammalian cells. The host cell attempts to silence the incoming viral genome by epigenetic mechanisms, but the viral VP16 and ICP0 proteins promote active chromatin on the viral genome by recruiting other host epigenetic factors. However, the dependence on VP16 and ICP0 differs in different cell lines, implying cell type-dependent functional contributions of epigenetic factors for HSV gene expression. In this study, we performed a targeted RNA interference (RNAi) screen for cellular chromatin factors that are involved in regulation of herpes simplex virus (HSV) gene expression in U2OS osteosarcoma cells, a cell line that complements ICP0 mutant and VP16 mutant virus replication. In this screen, we found the same general classes of chromatin factors that regulate HSV gene expression in U2OS cells as in other cell types, including histone demethylases (HDMs), histone deacetylases (HDACs), histone acetyltransferases (HATs), and chromatin-remodeling factors, but the specific factors within these classes are different from those identified previously for other cell types. For example, KDM3A and KDM1A (LSD1) both demethylate mono- and dimethylated H3K9, but KDM3A emerged in our screen of U2OS cells. Further, small interfering RNA (siRNA) and inhibitor studies support the idea that KDM1A is more critical in HeLa cells, as observed previously, while KDM3A is more critical in U2OS cells. These results argue that different cellular chromatin factors are critical in different cell lines to carry out the positive and negative epigenetic effects exerted on the HSV genome