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41.
David Lee Tjaart AP de Beer Roman A Laskowski Janet M Thornton Christine A Orengo 《BMC structural biology》2011,11(1):2
Background
The Midwest Center for Structural Genomics (MCSG) is one of the large-scale centres of the Protein Structure Initiative (PSI). During the first two phases of the PSI the MCSG has solved over a thousand protein structures. A criticism of structural genomics is that target selection strategies mean that some structures are solved without having a known function and thus are of little biomedical significance. Structures of unknown function have stimulated the development of methods for function prediction from structure. 相似文献42.
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43.
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.
相似文献
44.
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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45.
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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48.
Lysine is catabolized via the saccharopine pathway in plants and mammals. In this pathway, lysine is converted to α-aminoadipic-δ-semialdehyde (AASA) by lysine-ketoglutarate reductase/saccharopine dehydrogenase (LKR/SDH); thereafter, AASA is converted to aminoadipic acid (AAA) by α-aminoadipic-δ-semialdehyde dehydrogenase (AASADH). Here, we investigate the occurrence, genomic organization and functional role of lysine catabolic pathways among prokaryotes. Surprisingly, only 27 species of the 1478 analyzed contain the lkr and sdh genes, whereas 323 species contain aasadh orthologs. A sdh-related gene, identified in 159 organisms, was frequently found contiguously to an aasadh gene. This gene, annotated as lysine dehydrogenase (lysdh), encodes LYSDH an enzyme that directly converts lysine to AASA. Pipecolate oxidase (PIPOX) and lysine-6-aminotransferase (LAT), that converts lysine to AASA, were also found associated with aasadh. Interestingly, many lysdh–aasadh–containing organisms live under hyperosmotic stress. To test the role of the lysine-to-AASA pathways in the bacterial stress response, we subjected Silicibacter pomeroyi to salt stress. All but lkr, sdh, lysdh and aasadh were upregulated under salt stress conditions. In addition, lysine-supplemented culture medium increased the growth rate of S. pomeroyi under high-salt conditions and induced high-level expression of the lysdh–aasadh operon. Finally, transformation of Escherichia coli with the S. pomeroyi lysdh–aasadh operon resulted in increased salt tolerance. The transformed E. coli accumulated high levels of the compatible solute pipecolate, which may account for the salt resistance. These findings suggest that the lysine-to-AASA pathways identified in this work may have a broad evolutionary importance in osmotic stress resistance. 相似文献
49.
Phylogenetic analysis of slippage-like sequence variation in the V4 rRNA expansion segment in tiger beetles (Cicindelidae) 总被引:1,自引:1,他引:0
Sequence variation in the middle part of the small-subunit rRNA was studied
for representatives of the major groups in the family Cicindelidae
(Coleoptera). All taxa exhibited a much expanded segment in variable region
V4 compared to D. melanogaster. This expanded segment was not found in
other groups of beetles, including three taxa in the closely related
Carabidae. Secondary structure predictions indicate that the expanded
segment folds into a single stem-loop structure in all taxa. Despite its
structural conservation, the fragment differs strongly in primary sequence,
even between closely related sister taxa. Several features of these
sequences are consistent with slippage replication as the mechanism that
has generated this sequence variation: the level of internal sequence
repetition as measured by the relative simplicity factor (RSF), its
variation in length between close relatives, and the strong nucleotide bias
compared to the remainder of the gene. With few exceptions, there was also
a correlation between sequence length and the level of sequence repetition,
frequently interpreted as the result of slippage. Phylogenies inferred from
the expansion segment were not consistent with existing hypotheses from
other molecular data for the group. This indicates that DNA sequences in
this region are not homologous throughout the entire Cicindelidae, but it
leaves open the possibility that this expansion segment can be used for
phylogeny reconstruction within subgroups. The implications of a
phylogenetic approach to the understanding of slippage-like evolution are
discussed.
相似文献