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91.
Mingjian Shi Vadim Pedchenko Briana H. Greer Wade D. Van Horn Samuel A. Santoro Charles R. Sanders Billy G. Hudson Brandt F. Eichman Roy Zent Ambra Pozzi 《The Journal of biological chemistry》2012,287(42):35139-35152
Integrin α1β1 binding to collagen IV, which is mediated by the α1-inserted (I) domain, down-regulates collagen synthesis. When unligated, a salt bridge between Arg287 and Glu317 is thought to keep this domain in a low affinity conformation. Ligand binding opens the salt bridge leading to a high-affinity conformation. How modulating integrin α1β1 affinity alters collagen homeostasis is unknown. To address this question, we utilized a thermolysin-derived product of the α1α2α1 network of collagen IV (α1α2α1(IV) truncated protomer) that selectively binds integrin α1β1. We show that an E317A substitution enhanced binding to the truncated protomer, consistent with a previous finding that this substitution eliminates the salt bridge. Surprisingly, we show that an R287A substitution did not alter binding, whereas R287E/E317R substitutions enhanced binding to the truncated protomer. NMR spectroscopy and molecular modeling suggested that eliminating the Glu317 negative charge is sufficient to induce a conformational change toward the open state. Thus, the role played by Glu317 is largely independent of the salt bridge. We further show that cells expressing E317A or R287E/E317R substitutions have enhanced down-regulation of collagen IV synthesis, which is mediated by the ERK/MAPK pathway. In conclusion, we have demonstrated that modulating the affinity of the extracellular α1 I domain to collagen IV enhances outside-in signaling by potentiating ERK activation and enhancing the down-regulation of collagen synthesis. 相似文献
92.
Background
Experimental autoimmune encephalomyelitis (EAE), the best available model of multiple sclerosis, can be induced in different animal strains using immunization with central nervous system antigens. EAE is associated with inflammation and demyelination of the nervous system. Micro-array can be used to investigate gene expression and biological pathways that are altered during disease. There are few studies of the changes in gene expression in EAE, and these have mostly been done in a chronic mouse EAE model. EAE induced in the Lewis with myelin basic protein (MBP-EAE) is well characterised, making it an ideal candidate for the analysis of gene expression in this disease model.Methodology/Principal Findings
MBP-EAE was induced in female Lewis rats by inoculation with MBP and adjuvants. Total RNA was extracted from the spinal cords and used for micro-array analysis using AffimetrixGeneChip Rat Exon 1.0 ST Arrays. Gene expression in the spinal cords was compared between healthy female rats and female rats with MBP-EAE. Gene expression in the spinal cord of rats with MBP-EAE differed from that in the spinal cord of normal rats, and there was regulation of pathways involved with immune function and nervous system function. For selected genes the change in expression was confirmed with real-time PCR.Conclusions/Significance
EAE leads to modulation of gene expression in the spinal cord. We have identified the genes that are most significantly regulated in MBP-EAE in the Lewis rat and produced a profile of gene expression in the spinal cord at the peak of disease. 相似文献93.
94.
David M. Richards Emma Greer Azahara C. Martin Graham Moore Peter J. Shaw Martin Howard 《PLoS computational biology》2012,8(12)
The mechanism by which homologous chromosomes pair during meiosis, as a prelude to recombination, has long been mysterious. At meiosis, the telomeres in many organisms attach to the nuclear envelope and move together to form the telomere bouquet, perhaps to facilitate the homologous search. It is believed that diffusion alone is not sufficient to account for the formation of the bouquet, and that some directed movement is also required. Here we consider the formation of the telomere bouquet in a wheat-rye hybrid both experimentally and using mathematical modelling. The large size of the wheat nucleus and wheat''s commercial importance make chromosomal pairing in wheat a particularly interesting and important process, which may well shed light on pairing in other organisms. We show that, prior to bouquet formation, sister chromatid telomeres are always attached to a hemisphere of the nuclear membrane and tend to associate in pairs. We study a mutant lacking the Ph1 locus, a locus ensuring correct homologous chromosome pairing, and discover that bouquet formation is delayed in the wild type compared to the mutant. Further, we develop a mathematical model of bouquet formation involving diffusion and directed movement, where we show that directed movement alone is sufficient to explain bouquet formation dynamics. 相似文献
95.
96.
Developmental anomalies of central respiratory neural control contribute to newborn mortality and morbidity. Elucidation of the cellular, molecular, trophic, and genetic mechanisms involved in the formation and function of respiratory nuclei during prenatal development will provide a foundation for understanding pathologies. The pre-B?tzinger Complex (pre-B?tC) is a specific group of neurons located in the ventrolateral medulla that is critical for respiratory rhythmogenesis. Thus it has become a major focus of research. Here, we provide an overview of current knowledge regarding the anatomical and functional emergence of the rodent pre-B?tC during the prenatal period. 相似文献
97.
Shimada M Greer PA McMahon AP Bouxsein ML Schipani E 《The Journal of biological chemistry》2008,283(30):21002-21010
Calpains are intracellular cysteine proteases, which include widely expressed mu- and m-calpains (1). Both mu-calpains and m-calpains are heterodimers consisting of a large catalytic subunit and a small regulatory subunit. The calpain small subunit encoded by the gene Capn4 directly binds to the intracellular C-terminal tail (C-tail) of the receptor for parathyroid hormone and parathyroid hormone-related peptide and modulates its cellular functions in osteoblasts in vitro (2). To investigate a potential role of the calpain small subunit in osteoblasts in vivo, we generated osteoblast-specific Capn4 knock-out mice using the Cre-LoxP system (3). Mutant mice had smaller bodies with shorter limbs, reduced trabecular bone with thinner cortices, and decreased osteoblast number. In vitro analysis confirmed that deletion of Capn4 in osteoblasts severely affected multiple osteoblast functions including proliferation, differentiation, and matrix mineralization. Collectively, our findings provide the first in vivo demonstration that the calpain small subunit is essential for proper osteoblast activity and bone remodeling. 相似文献
98.
99.
Selection of Specific Endophytic Bacterial Genotypes by Plants in Response to Soil Contamination 总被引:10,自引:2,他引:8
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Steven D. Siciliano Nathalie Fortin Anca Mihoc Gesine Wisse Suzanne Labelle Danielle Beaumier Danielle Ouellette Real Roy Lyle G. Whyte M. Kathy Banks Paul Schwab Ken Lee Charles W. Greer 《Applied microbiology》2001,67(6):2469-2475
Plant-bacterial combinations can increase contaminant degradation in the rhizosphere, but the role played by indigenous root-associated bacteria during plant growth in contaminated soils is unclear. The purpose of this study was to determine if plants had the ability to selectively enhance the prevalence of endophytes containing pollutant catabolic genes in unrelated environments contaminated with different pollutants. At petroleum hydrocarbon contaminated sites, two genes encoding hydrocarbon degradation, alkane monooxygenase (alkB) and naphthalene dioxygenase (ndoB), were two and four times more prevalent in bacteria extracted from the root interior (endophytic) than from the bulk soil and sediment, respectively. In field sites contaminated with nitroaromatics, two genes encoding nitrotoluene degradation, 2-nitrotoluene reductase (ntdAa) and nitrotoluene monooxygenase (ntnM), were 7 to 14 times more prevalent in endophytic bacteria. The addition of petroleum to sediment doubled the prevalence of ndoB-positive endophytes in Scirpus pungens, indicating that the numbers of endophytes containing catabolic genotypes were dependent on the presence and concentration of contaminants. Similarly, the numbers of alkB- or ndoB-positive endophytes in Festuca arundinacea were correlated with the concentration of creosote in the soil but not with the numbers of alkB- or ndoB-positive bacteria in the bulk soil. Our results indicate that the enrichment of catabolic genotypes in the root interior is both plant and contaminant dependent. 相似文献
100.
John Westbrook Zukang Feng Shri Jain T. N. Bhat Narmada Thanki Veerasamy Ravichandran Gary L. Gilliland Wolfgang F. Bluhm Helge Weissig Douglas S. Greer Philip E. Bourne Helen M. Berman 《Nucleic acids research》2002,30(1):245-248
The Protein Data Bank (PDB; http://www.pdb.org/) is the single worldwide archive of structural data of biological macromolecules. This paper describes the progress that has been made in validating all data in the PDB archive and in releasing a uniform archive for the community. We have now produced a collection of mmCIF data files for the PDB archive (ftp://beta.rcsb.org/pub/pdb/uniformity/data/mmCIF/). A utility application that converts the mmCIF data files to the PDB format (called CIFTr) has also been released to provide support for existing software. 相似文献