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21.
Ganoderma microsporum immunomodulatory protein induces apoptosis and potentiates mitomycin C‐induced apoptosis in urinary bladder urothelial carcinoma cells
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22.
Synonymous substitution rates have been shown to vary among evolutionary
lineages of both nuclear and organellar genes across a broad range of
taxonomic groups. In animals, rate heterogeneity does not appear to be
correlated across nuclear and mitochondrial genes. In this paper, we
contrast substitution rates in two plant groups and show that grasses
evolve more rapidly than palms at synonymous sites in a mitochondrial, a
nuclear, and a plastid gene. Furthermore, we show that the relative rates
of synonymous substitution between grasses and palms are similar at the
three loci. The correlation in synonymous substitution rates across genes
is particularly striking because the three genes evolve at very different
absolute rates. In contrast, relative rates of nonsynonymous substitution
are not conserved among the three genes.
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23.
JC polyomavirus (JCPyV) is a common human pathogen that results in a chronic asymptomatic infection in healthy adults. Under conditions of immunosuppression, JCPyV spreads to the central nervous system and can cause the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML), a disease for which there are no vaccines or antiviral therapies. Retro-2 is a previously identified small molecule inhibitor that was originally shown to block retrograde transport of toxins such as ricin toxin from endosomes to the Golgi apparatus and endoplasmic reticulum (ER), and Retro-2.1 is a chemical analog of Retro-2 that has been shown to inhibit ricin intoxication of cells at low nanomolar concentrations. Retro-2 has previously been shown to prevent retrograde transport of JCPyV virions to the ER, but the effect of Retro-2.1 on JCPyV infectivity is unknown. Here it is shown that Retro-2.1 inhibits JCPyV with an EC50 of 3.9 μM. This molecule inhibits JCPyV infection at dosages that are not toxic to human tissue culture cells. Retro-2.1 was also tested against two other polyomaviruses, the human BK polyomavirus and simian virus 40, and was also shown to inhibit infection at similar concentrations. Viral uncoating studies demonstrate that Retro-2.1 inhibits BKPyV infectivity in a manner similar to Retro-2. These studies demonstrate that improved analogs of Retro-2 can inhibit infection at lower dosages than Retro-2 and further optimization of these compounds may lead to effective treatment options for those suffering from JCPyV infection and PML. 相似文献
24.
Background
The dynamic growing and shortening behaviors of microtubules are central to the fundamental roles played by microtubules in essentially all eukaryotic cells. Traditionally, microtubule behavior is quantified by manually tracking individual microtubules in time-lapse images under various experimental conditions. Manual analysis is laborious, approximate, and often offers limited analytical capability in extracting potentially valuable information from the data.Results
In this work, we present computer vision and machine-learning based methods for extracting novel dynamics information from time-lapse images. Using actual microtubule data, we estimate statistical models of microtubule behavior that are highly effective in identifying common and distinct characteristics of microtubule dynamic behavior.Conclusion
Computational methods provide powerful analytical capabilities in addition to traditional analysis methods for studying microtubule dynamic behavior. Novel capabilities, such as building and querying microtubule image databases, are introduced to quantify and analyze microtubule dynamic behavior.25.
The immunophenotype of HT29 human colon cancer cells implanted into severe combined immunodeficient mice was assessed in primary
tumours and their metastases in the lungs using an indirect immunohistochemical method. After primary tumours were surgically
removed, the metastases were given time to develop, thus paralleling the clinical situation. While vimentin was negative in
both primary and secondary tumours, E-cadherin was present as membrane-bound labelling in the primary tumours only. Whereas
the markers p53, MIB1, PCNA and CEA were consistently positive in both primary and metastatic tumours, CD44 variant 6 and
CA125 were negative in metastases but positive in the primary tumours. There was a significant increase in the percentage
of cells labelled for p53 in the primary tumours compared with the metastases. For the proliferation markers, there was no
significant difference in labelling between primary tumours and metastases for MIB1. Of the cytokeratins examined, CK 20 gave
the strongest and most consistent reaction in both primary and secondary tumours. The results indicate that, for certain immunohistochemical
markers, results are the same in both primary tumours and metastases. Hence, in these cases, antigens that are expressed on
the primary tumour as well as on the metastases can serve as target molecules for immunologically based forms of treatment
of metastases.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
26.
A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome 总被引:29,自引:24,他引:5
A model of DNA sequence evolution applicable to coding regions is
presented. This represents the first evolutionary model that accounts for
dependencies among nucleotides within a codon. The model uses the codon, as
opposed to the nucleotide, as the unit of evolution, and is parameterized
in terms of synonymous and nonsynonymous nucleotide substitution rates. One
of the model's advantages over those used in methods for estimating
synonymous and nonsynonymous substitution rates is that it completely
corrects for multiple hits at a codon, rather than taking a parsimony
approach and considering only pathways of minimum change between homologous
codons. Likelihood-ratio versions of the relative-rate test are constructed
and applied to data from the complete chloroplast DNA sequences of Oryza
sativa, Nicotiana tabacum, and Marchantia polymorpha. Results of these
tests confirm previous findings that substitution rates in the chloroplast
genome are subject to both lineage-specific and locus-specific effects.
Additionally, the new tests suggest tha the rate heterogeneity is due
primarily to differences in nonsynonymous substitution rates. Simulations
help confirm previous suggestions that silent sites are saturated, leaving
no evidence of heterogeneity in synonymous substitution rates.
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27.
Benzene, a known human rnyelotoxin and leukemogen is metabolized by liver cytochrome P-450 mono-oxygenase to phenol. Further hydroxylation of phenol by cytochrome P-450 monooxygenase results in the formation of mainly hydroquinone, which accumulates in the bone marrow. Bone marrow contains high levels of myeloperoxidase. Here we report that phenol hydroxylation to hydroquinone is also catalyzed by human myeloperoxidase in the presence of a superoxide anion radical generating system, hypoxanthine and xanthine oxidase. No hydroquinone formation was detected in the absence of myeloperoxidase. At low concentrations superoxide disniutase stimulated, but at high concentrations inhibited, the conversion of phenol to hydroquinone. The inhibitory effect at high superoxide dismutase concentrations indicates that the active hydroxylating species of myeloperoxidase is not derived from its interaction with hydrogen peroxide. Furthermore, catalase a hydrogen peroxide scavenger, was found to have no significant effect on hydroxylation of phenol to hydroquinone, supporting the lack of hydrogen peroxide involvement. Mannitol (a hydroxyl radical scavenger) was found to have no inhibitory effect, but histidine (a singlet oxygen scavenger) inhibited hydroquinone formation. Based on these results we postulate that a myeloperoxidase-superoxide complex spontaneously rearranges to generate singlet oxygen and that this singlet oxygen is responsible for phenol hydroxylation to hydroquinone. These results also suggest that myeloperoxidase dependent hydroquinone formation could play a role in the production and accumulation of hydroquinone in bone marrow, the target organ of benzene-induced myelotoxicity. 相似文献
28.
Functional polymorphisms in PRODH are associated with risk and protection for schizophrenia and fronto-striatal structure and function
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Kempf L Nicodemus KK Kolachana B Vakkalanka R Verchinski BA Egan MF Straub RE Mattay VA Callicott JH Weinberger DR Meyer-Lindenberg A 《PLoS genetics》2008,4(11):e1000252
PRODH, encoding proline oxidase (POX), has been associated with schizophrenia through linkage, association, and the 22q11 deletion syndrome (Velo-Cardio-Facial syndrome). Here, we show in a family-based sample that functional polymorphisms in PRODH are associated with schizophrenia, with protective and risk alleles having opposite effects on POX activity. Using a multimodal imaging genetics approach, we demonstrate that haplotypes constructed from these risk and protective functional polymorphisms have dissociable correlations with structure, function, and connectivity of striatum and prefrontal cortex, impacting critical circuitry implicated in the pathophysiology of schizophrenia. Specifically, the schizophrenia risk haplotype was associated with decreased striatal volume and increased striatal-frontal functional connectivity, while the protective haplotype was associated with decreased striatal-frontal functional connectivity. Our findings suggest a role for functional genetic variation in POX on neostriatal-frontal circuits mediating risk and protection for schizophrenia. 相似文献
29.
30.