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41.
The fact that there is very little if any overlap between the genes of different prognostic signatures for early-discovery breast cancer is well documented. The reasons for this apparent discrepancy have been explained by the limits of simple machine-learning identification and ranking techniques, and the biological relevance and meaning of the prognostic gene lists was questioned. Subsequently, proponents of the prognostic gene lists claimed that different lists do capture similar underlying biological processes and pathways. The present study places under scrutiny the validity of this claim, for two important gene lists that are at the focus of current large-scale validation efforts. We performed careful enrichment analysis, controlling the effects of multiple testing in a manner which takes into account the nested dependent structure of gene ontologies. In contradiction to several previous publications, we find that the only biological process or pathway for which statistically significant concordance can be claimed is cell proliferation, a process whose relevance and prognostic value was well known long before gene expression profiling. We found that the claims reported by others, of wider concordance between the biological processes captured by the two prognostic signatures studied, were found either to be lacking statistical rigor or were in fact based on addressing some other question. 相似文献
42.
43.
E Ozkaynak P N Schnegelsberg D F Jin G M Clifford F D Warren E A Drier H Oppermann 《The Journal of biological chemistry》1992,267(35):25220-25227
Osteogenic protein-2, OP-2, a new member of the transforming growth factor-beta (TGF-beta) superfamily, closely related to the osteogenic/bone morphogenetic proteins, was discovered in mouse embryo and human hippocampus cDNA libraries. The TGF-beta domain of OP-2 shows 74% identity to OP-1, 75% to Vgr-1, and 76% to BMP-5, hence OP-2 may also have bone inductive activity. The genomic locus of OP-2 has seven exons, like OP-1, and spans more than 27 kilobases (kb). In the C-terminal TGF-beta domain, OP-2 has a unique additional cysteine. Mouse embryos express relatively high levels of OP-2 mRNA at 8 days, two species of 3 and 5 kb. A careful study of mRNA expression of the osteogenic proteins in specific organs revealed discrete mRNA species for BMP-3, BMP-4, BMP-5, and BMP-6/Vgr-1 in lung or liver of young and adult mice. OP-1 is expressed in kidney; however, OP-2 and BMP-2 mRNAs were not detected in any organs studied, suggesting an early developmental role. 相似文献
44.
A model of the carbohydrate recognition domain CRD, residues 111-245, of
hamster galectin-3 has been made using homology modeling and dynamics
minimization methods. The model is based on the known x-ray structures of
bovine galectin-1 and human galectin-2. The oligosaccharides
NeuNAc-alpha2,3-Gal-beta1,4-Glc and GalNAc-alpha1, 3-
[Fuc-alpha1,2]-Gal-beta1,4-Glc, known to be specific high-affinity ligands
for galectin-3, as well as lactose recognized by all galectins were docked
in the galectin-3 CRD model structure and a minimized binding conformation
found in each case. These studies indicate a putative extended
carbohydrate-binding subsite in the hamster galectin- 3 involving Arg139,
Glu230, and Ser232 for NeuNAc-alpha2,3-; Arg139 and Glu160 for
fucose-alpha1,2-; and Arg139 and Ile141 for GalNAc-alpha1,3- substituents
on the primary galactose. Each of these positions is variable within the
whole galectin family. Two of these residues, Arg139 and Ser232, were
selected for mutagenesis to probe their importance in this newly identified
putative subsite. Residue 139 adopts main-chain dihedral angles
characteristic of an isolated bridge structural feature, while residue 232
is the C-terminal residue of beta- strand-11, and is followed immediately
by an inverse gamma-turn. A systematic series of mutant proteins have been
prepared to represent the residue variation present in the aligned
sequences of galectins-1, - 2, and -3. Minimized docked models were
generated for each mutant in complex with NeuNAc-alpha2,3-Gal-beta1,4-Glc,
GalNAc-alpha1, 3-[Fuc- alpha1,2]-Gal-beta1,4- Glc, and Gal-beta1,4-Glc.
Correlation of the computed protein-carbohydrate interaction energies for
each lectin- oligosaccharide pair with the experimentally determined
binding affinities for fetuin and asialofetuin or the relative potencies of
lactose and sialyllactose in inhibiting binding to asiolofetuin is
consistent with the postulated key importance of Arg139 in recognition of
the extended sialylated ligand.
相似文献
45.
Nucleotide sequence analysis of the human salivary protein genes HIS1 and HIS2, and evolution of the STATH/HIS gene family 总被引:1,自引:0,他引:1
Human histatins are a family of low-M(r), neutral to very basic,
histidine-rich salivary polypeptides. They probably function as part of the
nonimmune host defense system in the oral cavity. A 39-kb region of DNA
containing the HIS1 and HIS2 genes was isolated from two human genomic
phage libraries as a series of overlapping clones. The nucleotide sequences
of the HIS1 gene and part of the HIS2(1) gene were determined. The
transcribed region of HIS1 spans 8.5 kb and contains six exons and five
introns. The HIS1 and HIS2(1) genes exhibit 89% overall sequence identity,
with exon sequences exhibiting 95% identity. The two loci probably arose by
a gene duplication event approximately 15-30 Mya. The HIS1 sequence data
were also compared with that of STATH. Human statherin is a low-M(r) acidic
phosphoprotein that acts as an inhibitor of precipitation of calcium
phosphate salts in the oral cavity. The HIS1 and STATH genes show nearly
identical overall gene structures. The HIS1 and STATH loci exhibit 77%-81%
sequence identity in intron DNA and 80%-88% sequence identity in noncoding
exons but only 38%-43% sequence identity in the protein-coding regions of
exons 4 and 5. These unusual data suggest that HIS1, HIS2, and STATH belong
to a single gene family exhibiting accelerated evolution between the HIS
and STATH coding sequences.
相似文献
46.
Evolution of the Adh locus in the Drosophila willistoni group: the loss of an intron, and shift in codon usage 总被引:1,自引:0,他引:1
We report here the DNA sequence of the alcohol dehydrogenase gene (Adh)
cloned from Drosophila willistoni. The three major findings are as follows:
(1) Relative to all other Adh genes known from Drosophila, D. willistoni
Adh has the last intron precisely deleted; PCR directly from total genomic
DNA indicates that the deletion exists in all members of the willistoni
group but not in any other group, including the closely related saltans
group. Otherwise the structure and predicted protein are very similar to
those of other species. (2) There is a significant shift in codon usage,
especially compared with that in D. melanogaster Adh. The most striking
shift is from C to U in the wobble position (both third and first
position). Unlike the codon-usage-bias pattern typical of highly biased
genes in D. melanogaster, including Adh, D. willistoni has nearly 50% G + C
in the third position. (3) The phylogenetic information provided by this
new sequence is in agreement with almost all other molecular and
morphological data, in placing the obscura group closer to the melanogaster
group, with the willistoni group farther distant but still clearly within
the subgenus Sophophora.
相似文献
47.
An exception to the generally conservative nature of plastid gene evolution
is the gene coding for the beta" subunit of RNA polymerase, rpoC2. Previous
work by others has shown that maize and rice have an insertion in the
coding region of rpoC2, relative to spinach and tobacco. To assess the
distribution of this extra coding sequence, we surveyed a broad
phylogenetic sample comprising 55 species from 17 angiosperm families by
using Southern hybridization. The extra coding sequence is restricted to
the grasses (Poaceae). DNA sequence analysis of 11 species from all five
subfamilies within the grass family demonstrates that the extra sequence in
the coding region of rpoC2 is a repetitive array that exhibits more than a
twofold increase in nucleotide substitution, as well as a large number of
insertion/deletion events, relative to the adjacent flanking sequences. The
structure of the array suggests that slipped-strand mispairing causes the
repeated motifs and adds to the mechanisms through which the coding
sequence of plastid genes are known to evolve. Phylogenetic analyses based
on the sequence data from grass species support several relationships
previously suggested by morphological work, but they are ambiguous about
broad relationships within the family.
相似文献
48.
49.
Background
The Burkholderia cepacia complex (Bcc) is a collection of nine genotypically distinct but phenotypically similar species. They show wide ecological diversity and include species that are used for promoting plant growth and bio-control as well species that are opportunistic pathogens of vulnerable patients. Over recent years the Bcc have emerged as problematic pathogens of the CF lung. Pseudomonas aeruginosa is another important CF pathogen. It is able to synthesise hydrogen cyanide (HCN), a potent inhibitor of cellular respiration. We have recently shown that HCN production by P. aeruginosa may have a role in CF pathogenesis. This paper describes an investigation of the ability of bacteria of the Bcc to make HCN. 相似文献50.
Katarina EA Nostell Birgitta Essén-Gustavsson Johan T Bröjer 《Acta veterinaria Scandinavica》2012,54(1):7