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41.
Network analysis of temporal functionalities of the gut induced by perturbations in new-born piglets
Nirupama Benis Dirkjan Schokker Maria Suarez-Diez Vitor AP Martins dos Santos Hauke Smidt Mari A Smits 《BMC genomics》2015,16(1)
Background
Evidence is accumulating that perturbation of early life microbial colonization of the gut induces long-lasting adverse health effects in individuals. Understanding the mechanisms behind these effects will facilitate modulation of intestinal health. The objective of this study was to identify biological processes involved in these long lasting effects and the (molecular) factors that regulate them. We used an antibiotic and the same antibiotic in combination with stress on piglets as an early life perturbation. Then we used host gene expression data from the gut (jejunum) tissue and community-scale analysis of gut microbiota from the same location of the gut, at three different time-points to gauge the reaction to the perturbation. We analysed the data by a new combination of existing tools. First, we analysed the data in two dimensions, treatment and time, with quadratic regression analysis. Then we applied network-based data integration approaches to find correlations between host gene expression and the resident microbial species.Results
The use of a new combination of data analysis tools allowed us to identify significant long-lasting differences in jejunal gene expression patterns resulting from the early life perturbations. In addition, we were able to identify potential key gene regulators (hubs) for these long-lasting effects. Furthermore, data integration also showed that there are a handful of bacterial groups that were associated with temporal changes in gene expression.Conclusion
The applied systems-biology approach allowed us to take the first steps in unravelling biological processes involved in long lasting effects in the gut due to early life perturbations. The observed data are consistent with the hypothesis that these long lasting effects are due to differences in the programming of the gut immune system as induced by the temporary early life changes in the composition and/or diversity of microbiota in the gut.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1733-8) contains supplementary material, which is available to authorized users. 相似文献42.
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43.
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44.
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
45.
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.
相似文献
46.
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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Nimmy Mohan Sudheesh AP Nimmy Francis Richard Anderson Rakesh S. Laishram 《Nucleic acids research》2015,43(14):7005-7020
Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3′-end processing. 相似文献