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51.
Background
Affymetrix High Density Oligonuclotide Arrays (HDONA) simultaneously measure expression of thousands of genes using millions of probes. We use correlations between measurements for the same gene across 6685 human tissue samples from NCBI's GEO database to indicated the quality of individual HG-U133A probes. Low correlation indicates a poor probe. 相似文献52.
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Insight into the mechanisms of enhanced retinal transduction by the engineered AAV2 capsid variant ‐7m8
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Papakonstantinou E; Karakiulakis G; Eickelberg O; Perruchoud AP; Block LH; Roth M 《Glycobiology》1998,8(8):821-830
The formation of atherosclerotic lesions is characterized by invasion of
vascular smooth muscle cells (VSMC) into the tunica intima of the arterial
wall and subsequently by increased proliferation of VSMC, a process
apparently restricted to the intimal layer of blood vessels. Both events
are preceded by the pathological overexpression of several growth factors,
such as platelet-derived growth factor (PDGF) which is a potent mitogen for
VSMC and can induce their chemotaxis. PDGF is generally not expressed in
the normal artery but it is upregulated in atherosclerotic lesions. We have
previously shown that PDGF-BB specifically stimulates proliferating VSMC to
secrete a 340 kDa hyaluronic acid (HA-340). Here, we present evidence
regarding the biological functions of this glycan. We observed that HA-340
inhibited the PDGF-induced proliferation of human VSMC in a dose-dependent
manner and enhanced the PDGF-dependent invasion of VSMC through a basement
membrane barrier. These effects were abolished following treatment of
HA-340 with hyaluronidase. The effect of HA-340 on the PDGF-dependent
invasion of VSMC coincided with increased secretion of the 72-kDa type IV
collagenase by VSMC and was completely blocked by GM6001, a hydroxamic acid
inhibitor of matrix metalloproteinases. HA-340 did not exert any
chemotactic potency, nor did it affect chemotaxis of VSMC along a PDGF
gradient. In human atheromatic aortas, we found that HA- 340 is expressed
with a negative concentration gradient from the tunica media to the tunica
intima and the atheromatic plaque. Our findings suggest that HA-340 may be
linked to the pathogenesis of atherosclerosis, by modulating VSMC
proliferation and invasion.
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55.
Protein evolution in different cellular environments: cytochrome b in sharks and mammals 总被引:4,自引:0,他引:4
DNA sequences for the mitochondrial cytochrome b gene were determined for
13 species of sharks. Rates and patterns of amino acid replacement are
compared for sharks and mammals. Absolute rates of cytochrome b evolution
are six times slower in sharks than in mammals. Bivariate plots of the
number of nonsynonymous and silent transversions are indistinguishable in
the two groups, however, suggesting that the differences in amino acid
replacement rates are due primarily to differences in DNA substitution
rates. Patterns of amino acid replacement are also similar in the two
groups. Conserved and variable regions occur in the same parts of the
cytochrome b gene, and there is little evidence that the types of amino
acid changes are significantly different between the groups. Similarity in
the relative rates and patterns of protein change between the two groups
prevails despite dramatic differences in the cellular environments of
sharks and mammals. Poor penetrance of physiological differences through to
rates of protein evolution provides support for the neutral theory and
suggests that, for cytochrome b, patterns of evolution have been relatively
constant throughout much of vertebrate history.
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56.
Distribution of the molossinus allele of Sry, the testis-determining gene, in wild mice 总被引:3,自引:0,他引:3
Nagamine CM; Shiroishi T; Miyashita N; Tsuchiya K; Ikeda H; Takao N; Wu XL; Jin ML; Wang FS; Kryukov AP 《Molecular biology and evolution》1994,11(6):864-874
When the Y chromosome of the laboratory inbred mouse strain C57BL/6 (B6) is
replaced by the Y of certain strains of Mus musculus domesticus, testis
determination fails and all XY fetuses develop either as hermaphrodites or
XY females (XY sex reversal). This suggests the presence of at least two
alleles of Sry, the male-determining gene on the Y:M. m. domesticus and B6.
The B6 Y chromosome is derived from the Japanese house mouse, M. m.
molossinus and therefore carries a molossinus Sry allele. As a first step
to determine how the molossinus Sry allele evolved, its distribution
pattern was determined in wild mice. The cumulative data of 96 M. musculus
samples obtained from 58 geographical locations in Europe, North Africa,
and Asia show the molossinus Sry allele is restricted to Japan and the
neighboring Asian mainland and confirm that Japanese M. m. molossinus mice
were derived in part from a race of M. m. musculus from Korea or Manchuria.
Sry polymorphisms, as illustrated by the molossinus Sry allele, can serve
as molecular markers for studies on the evolution of wild M. musculus
populations and can help determine the role sex determination plays in
speciation.
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Kostic C Crippa SV Pignat V Bemelmans AP Samardzija M Grimm C Wenzel A Arsenijevic Y 《PloS one》2011,6(2):e16588
Cone photoreceptors mediate visual acuity under daylight conditions, so loss of cone-mediated central vision of course dramatically affects the quality of life of patients suffering from retinal degeneration. Therefore, promoting cone survival has become the goal of many ocular therapies and defining the stage of degeneration that still allows cell rescue is of prime importance. Using the Rpe65(R91W/R91W) mouse, which carries a mutation in the Rpe65 gene leading to progressive photoreceptor degeneration in both patients and mice, we defined stages of retinal degeneration that still allow cone rescue. We evaluated the therapeutic window within which cones can be rescued, using a subretinal injection of a lentiviral vector driving expression of RPE65 in the Rpe65(R91W/R91W) mice. Surprisingly, when applied to adult mice (1 month) this treatment not only stalls or slows cone degeneration but, actually, induces cone-specific protein expression that was previously absent. Before the intervention only part of the cones (40% of the number found in wild-type animals) in the Rpe65(R91W/R91W) mice expressed cone transducin (GNAT2); this fraction increased to 64% after treatment. Correct S-opsin localization is also recovered in the transduced region. In consequence these results represent an extended therapeutic window compared to the Rpe65(-/-) mice, implying that patients suffering from missense mutations might also benefit from a prolonged therapeutic window. Moreover, cones are not only rescued during the course of the degeneration, but can actually recover their initial status, meaning that a proportion of altered cones in chromophore deficiency-related disease can be rehabilitated even though they are severely affected. 相似文献