631 research outputs found
A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature
AbstractThe spike (S) glycoprotein of coronavirus is responsible for receptor binding and membrane fusion. A number of variants with deletions and mutations in the S protein have been isolated from naturally and persistently infected animals and tissue cultures. Here, we report the emergence and isolation of two temperature sensitive (ts) mutants and a revertant in the process of cold-adaptation of coronavirus infectious bronchitis virus (IBV) to a monkey kidney cell line. The complete sequences of wild type (wt) virus, two ts mutants, and the revertant were compared and variations linked to phenotypes were mapped. A single amino acid reversion (L294-to-Q) in the S protein is sufficient to abrogate the ts phenotype. Interestingly, unlike wt virus, the revertant grows well at and below 32 °C, the permissive temperature, as it carries other mutations in multiple genes that might be associated with the cold-adaptation phenotype. If the two ts mutants were allowed to enter cells at 32 °C, the S protein was synthesized, core-glycosylated and at least partially modified at 40 °C. However, compared with wt virus and the revertant, no infectious particles of these ts mutants were assembled and released from the ts mutant-infected cells at 40 °C. Evidence presented demonstrated that the Q294-to-L294 mutation, located at a highly conserved domain of the S1 subunit, might hamper processing of the S protein to a matured 180-kDa, endo-glycosidase H-resistant glycoprotein and the translocation of the protein to the cell surface. Consequently, some essential functions of the S protein, including mediation of cell-to-cell fusion and its incorporation into virions, were completely abolished
New lanostanes and naphthoquinones isolated from Antrodia salmonea and their antioxidative burst activity in human leukocytes
Four new compounds were isolated from the basidiomata of the fungus Antrodia salmonea, a newly identified species of Antrodia (Aphyllophorales) in Taiwan. These new compounds are named as lanosta-8,24-diene-3 beta,15 alpha,21-triol (1), 24-methylenelanost-8-ene-3 beta,15 alpha,21-triol (2), 2,3-dimethoxy-5-(2',5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]-naphthoquinone (3), and 2,3-dimethoxy-6-(2,5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]-naphthoquinone (4), respectively. Their structures were elucidated by spectroscopic methods. An in vitro cellular functional assay was performed to evaluate their anti-oxidative burst activity in human leukocytes. They showed inhibitory effects against phorbol 12-myristate-13-acetate (PMA), a direct protein kinase C activator, induced oxidative burst in neutrophils (PMN) and mononuclear cells (MNC) with 50% inhibitory concentration (IC50) ranging from 3.5 to 25.8 mu M. The potency order of these compounds in PMA-activated leukocytes was as 1 > 3 > 4 > 2. They were relatively less effective in formyl-Met-Leu-Phe (fMLP), a G-protein coupled receptor agonist, induced oxidative burst, except for compounds 3 and 4 in fMLP-activated PMN. These results indicated that three (1, 3, and 4) of these four newly identified compounds displayed antioxidative effect in human leukocytes with different potency and might confer anti-inflammatory activity to these drugs
Andrographolide Inhibits PI3K/AKT-Dependent NOX2 and iNOS Expression Protecting Mice against Hypoxia/Ischemia-Induced Oxidative Brain Injury
This study aimed to explore the mechanisms by which andrographolide protects against hypoxia-induced oxidative/nitrosative brain injury provoked by cerebral ischemic/reperfusion (CI/R) injury in mice. Hypoxia in vitro was modeled using oxygen-glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone CI/R injury with andrographolide (10-100 mu g/kg, i.v.) at 1 h after hypoxia ameliorated CI/R-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. CI/R induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significant increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (NOX2), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b cells due to activation of nuclear factor-kappa B (NF-kappa B) and hypoxia-inducible factor 1-alpha (HIF-1 alpha). All these changes were significantly diminished by andrographolide. In BV-2 cells, OGD induced ROS and nitric oxide production by upregulating NOX2 and iNOS via the phosphatidylinositol-3-kinase (PI3K)/AKT-dependent NF-kappa B and HIF-1 alpha pathways, and these changes were suppressed by andrographolide and LY294002. Our results indicate that andrographolide reduces NOX2 and iNOS expression possibly by impairing PI3K/AKT-dependent NF-kappa B and HIF-1 alpha activation. This compromises microglial activation, which then, in turn, mediates andrographolide's protective effect in the CI/R mice
The instability of Alexander-McTague crystals and its implication for nucleation
We show that the argument of Alexander and McTague, that the bcc crystalline
structure is favored in those crystallization processes where the first order
character is not too pronounced, is not correct. We find that any solution that
satisfies the Alexander-McTague condition is not stable. We investigate the
implication of this result for nucleation near the pseudo- spinodal in
near-meanfield systems.Comment: 20 pages, 0 figures, submitted to Physical Review
Upregulation of Haploinsufficient Gene Expression in the Brain by Targeting a Long Non-coding RNA Improves Seizure Phenotype in a Model of Dravet Syndrome
AbstractDravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism controlling the expression of SCN1A that is mediated by an antisense non-coding RNA (SCN1ANAT). Using oligonucleotide-based compounds (AntagoNATs) targeting SCN1ANAT we were able to induce specific upregulation of SCN1A both in vitro and in vivo, in the brain of Dravet knock-in mouse model and a non-human primate. AntagoNAT-mediated upregulation of Scn1a in postnatal Dravet mice led to significant improvements in seizure phenotype and excitability of hippocampal interneurons. These results further elucidate the pathophysiology of Dravet syndrome and outline a possible new approach for the treatment of this and other genetic disorders with similar etiology
Search for the Rare Decays J/Psi --> Ds- e+ nu_e, J/Psi --> D- e+ nu_e, and J/Psi --> D0bar e+ e-
We report on a search for the decays J/Psi --> Ds- e+ nu_e + c.c., J/Psi -->
D- e+ nu_e + c.c., and J/Psi --> D0bar e+ e- + c.c. in a sample of 5.8 * 10^7
J/Psi events collected with the BESII detector at the BEPC. No excess of signal
above background is observed, and 90% confidence level upper limits on the
branching fractions are set: B(J/Psi --> Ds- e+ nu_e + c.c.)<4.8*10^-5, B(J/Psi
--> D- e+ nu_e + c.c.) D0bar e+ e- + c.c.)<1.1*10^-5Comment: 10 pages, 4 figure
Measurements of psi(2S) decays to octet baryon-antibaryon pairs
With a sample of 14 million psi(2S) events collected by the BESII detector at
the Beijing Electron Positron Collider (BEPC), the decay channels psi(2S)->p
p-bar, Lambda Lambda-bar, Sigma0 Sigma0-bar, Xi Xi-bar are measured, and their
branching ratios are determined to be (3.36+-0.09+-0.24)*10E-4,
(3.39+-0.20+-0.32)*10E-4, (2.35+-0.36+-0.32)*10E-4, (3.03+-0.40+-0.32)*10E-4,
respectively. In the decay psi(2S)->p p-bar, the angular distribution parameter
alpha is determined to be 0.82+-0.17+-0.04.Comment: 8 pages, 8 figure
Partial Wave Analysis of
BES data on are presented. The
contribution peaks strongly near threshold. It is fitted with a
broad resonance with mass MeV, width MeV. A broad resonance peaking at 2020 MeV is also required
with width MeV. There is further evidence for a component
peaking at 2.55 GeV. The non- contribution is close to phase
space; it peaks at 2.6 GeV and is very different from .Comment: 15 pages, 6 figures, 1 table, Submitted to PL
Measurements of the observed cross sections for exclusive light hadron production in e^+e^- annihilation at \sqrt{s}= 3.773 and 3.650 GeV
By analyzing the data sets of 17.3 pb taken at GeV
and 6.5 pb taken at GeV with the BESII detector at the
BEPC collider, we have measured the observed cross sections for 12 exclusive
light hadron final states produced in annihilation at the two energy
points. We have also set the upper limits on the observed cross sections and
the branching fractions for decay to these final states at 90%
C.L.Comment: 8 pages, 5 figur
Partial wave analysis of J/\psi \to \gamma \phi \phi
Using events collected in the BESII detector, the
radiative decay is
studied. The invariant mass distribution exhibits a near-threshold
enhancement that peaks around 2.24 GeV/.
A partial wave analysis shows that the structure is dominated by a
state () with a mass of
GeV/ and a width of GeV/. The
product branching fraction is: .Comment: 11 pages, 4 figures. corrected proof for journa
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