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31.
32.
The early adaptive evolution of calmodulin 总被引:7,自引:0,他引:7
Baba ML; Goodman M; Berger-Cohn J; Demaille JG; Matsuda G 《Molecular biology and evolution》1984,1(6):442-455
Interaction between gene duplication and natural selection in molecular
evolution was investigated utilizing a phylogenetic tree constructed by the
parsimony procedure from amino acid sequences of 50 calmodulin- family
protein members. The 50 sequences, belonging to seven protein lineages
related by gene duplication (calmodulin itself, troponin-C, alkali and
regulatory light chains of myosin, parvalbumin, intestinal calcium-binding
protein, and glial S-100 phenylalanine-rich protein), came from a wide
range of eukaryotic taxa and yielded a denser tree (more branch points
within each lineage) than in earlier studies. Evidence obtained from the
reconstructed pattern of base substitutions and deletions in these
ancestral loci suggests that, during the early history of the family,
selection acted as a transforming force on expressed genes among the
duplicates to encode molecular sites with new or modified functions. In
later stages of descent, however, selection was a conserving force that
preserved the structures of many coadapted functional sites. Each branch of
the family was found to have a unique average tempo of evolutionary change,
apparently regulated through functional constraints. Proteins whose
functions dictate multiple interaction with several other macromolecules
evolved more slowly than those which display fewer protein-protein and
protein-ion interactions, e.g., calmodulin and next troponin-C evolved at
the slowest average rates, whereas parvalbumin evolved at the fastest. The
history of all lineages, however, appears to be characterized by rapid
rates of evolutionary change in earlier periods, followed by slower rates
in more recent periods. A particularly sharp contrast between such fast and
slow rates is found in the evolution of calmodulin, whose rate of change in
earlier eukaryotes was manyfold faster than the average rate over the past
1 billion years. In fact, the amino acid replacements in the nascent
calmodulin lineage occurred at residue positions that in extant metazoans
are largely invariable, lending further support to the Darwinian hypothesis
that natural selection is both a creative and a conserving force in
molecular evolution.
相似文献
33.
Proteolytic enzymes have been used both to modify properties of the cell membrane and to dissociate cells from many tissues including pituitary (4, 5, 12). Exposure of secretory tissues to pronase can alter their secretory response. Thus incubation of pancreatic islets of Langerhans in the presence of low concentrations of pronase increased the subsequent release of insulin in the presence of stimulatory and nonstimulatory glucose concentrations (7). The purpose of the present investigation was to determine whether low concentrations of pronase have the same stimulatory effect on the release of a pituitary hormone, growth hormone. Such an effect on hormone release could be of some importance in view of the development of dissociated cell systems as models for the study of the control of hormone release (4, 5). 相似文献
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35.
Xystrakis E Cavailles P Dejean AS Cautain B Colacios C Lagrange D van de Gaar MJ Bernard I Gonzalez-Dunia D Damoiseaux J Fournié GJ Saoudi A 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(5):3140-3147
Differential cytokine production by T cells plays an important role in the outcome of the immune response. We show that the level of CD45RC expression differentiates rat CD8 T cells in two subpopulations, CD45RC(high) and CD45RC(low), that have different cytokine profiles and functions. Upon in vitro stimulation, in an Ag-presenting cell-independent system, CD45RC(high) CD8 T cells produce IL-2 and IFN-gamma while CD45RC(low) CD8 T cells produce IL-4, IL-10, and IL-13. In vitro, these subsets also exhibit different cytotoxic and suppressive functions. The CD45RC(high)/CD45RC(low) CD8 T cell ratio was determined in Lewis (LEW) and Brown-Norway (BN) rats. These two rat strains differ with respect to the Th1/Th2 polarization of their immune responses and to their susceptibility to develop distinct immune diseases. The CD45RC(high)/CD45RC(low) CD8 T cell ratio is higher in LEW than in BN rats, and this difference is dependent on hemopoietic cells. Linkage analysis in a F(2)(LEW x BN) intercross identified two quantitative trait loci on chromosomes 9 and 20 controlling the CD45RC(high)/CD45RC(low) CD8 T cell ratio. This genetic control was confirmed in congenic rats. The region on chromosome 9 was narrowed down to a 1.2-cM interval that was found to also control the IgE response in a model of Th2-mediated disorder. Identification of genes that control the CD45RC(high)/CD45RC(low) CD8 T cell subsets in these regions could be of great interest for the understanding of the pathophysiology of immune-mediated diseases. 相似文献
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C André Lévesque Henk Brouwer Liliana Cano John P Hamilton Carson Holt Edgar Huitema Sylvain Raffaele Gregg P Robideau Marco Thines Joe Win Marcelo M Zerillo Gordon W Beakes Jeffrey L Boore Dana Busam Bernard Dumas Steve Ferriera Susan I Fuerstenberg Claire MM Gachon Elodie Gaulin Francine Govers Laura Grenville-Briggs Neil Horner Jessica Hostetler Rays HY Jiang Justin Johnson Theerapong Krajaejun Haining Lin Harold JG Meijer Barry Moore Paul Morris Vipaporn Phuntmart Daniela Puiu Jyoti Shetty Jason E Stajich Sucheta Tripathy Stephan Wawra Pieter van West Brett R Whitty Pedro M Coutinho Bernard Henrissat Frank Martin Paul D Thomas Brett M Tyler Ronald P De Vries Sophien Kamoun Mark Yandell Ned Tisserat C Robin Buell 《Genome biology》2010,11(7):1-22
38.
39.
Smolders J Peelen E Thewissen M Cohen Tervaert JW Menheere P Hupperts R Damoiseaux J 《PloS one》2010,5(12):e15235
Background
A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures.Methodology/Principal Findings
Fifteen RRMS patients were supplemented with 20 000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31–175) at week 0 to 380 nmol/L (151–535) at week 12 (P<0.001). During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory) CD4+ Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P = 0.143). An increased proportion of IL-10+ CD4+ T cells was found after supplementation (P = 0.021). Additionally, a decrease of the ratio between IFN-γ+ and IL-4+ CD4+ T cells was observed (P = 0.035).Conclusion/Significance
Twelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials.Trial Registration
Clinicaltrials.gov NCT00940719相似文献40.
Poulos JL Jeon TJ Damoiseaux R Gillespie EJ Bradley KA Schmidt JJ 《Biosensors & bioelectronics》2009,24(6):1806-1810
Measurements of ion channels are important for scientific, sensing and pharmaceutical applications. Reconstitution of ion channels into lipid vesicles and planar lipid bilayers for measurement at the single molecule level is a laborious and slow process incompatible with the high throughput methods and equipment used for sensing and drug discovery. A recently published method of lipid bilayer formation mechanically combines lipid monolayers self-assembled at the interfaces of aqueous and apolar phases. We have expanded on this method by vertically orienting these phases and using gravity as the driving force to combine the monolayers. As this method only requires fluid dispensation, it is trivially integrated with high throughput automated liquid-handling robotics. In a proof-of-concept demonstration, we created over 2200 lipid bilayers in 3h. We show single molecule measurements of technologically and physiologically relevant ion channels incorporated into lipid bilayers formed with this method. 相似文献