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31.
Wither J Cai YC Lim S McKenzie T Roslin N Claudio JO Cooper GS Hudson TJ Paterson AD Greenwood CM Gladman D Pope J Pineau CA Smith CD Hanly JG Peschken C Boire G;CaNIOS Investigators Fortin PR 《Arthritis research & therapy》2008,10(5):R108-13
Introduction
Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives.Methods
Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry.Results
We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait.Conclusions
The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity. 相似文献32.
33.
A report on the First International Symposium of the Austrian Proteomics Platform, Seefeld, Austria, 26-29 January 2004. 相似文献
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Background
In many areas of medical research, a bivariate analysis is desirable because it simultaneously tests two response variables that are of equal interest and importance in two populations. Several parametric and nonparametric bivariate procedures are available for the location problem but each of them requires a series of stringent assumptions such as specific distribution, affine-invariance or elliptical symmetry. 相似文献36.
Choi DW Zea CJ Do YS Semrau JD Antholine WE Hargrove MS Pohl NL Boyd ES Geesey GG Hartsel SC Shafe PH McEllistrem MT Kisting CJ Campbell D Rao V de la Mora AM Dispirito AA 《Biochemistry》2006,45(5):1442-1453
To examine the potential role of methanobactin (mb) as the extracellular component of a copper acquisition system in Methylosinus trichosporium OB3b, the metal binding properties of mb were examined. Spectral (UV-visible, fluorescence, and circular dichroism), kinetic, and thermodynamic data suggested copper coordination changes at different Cu(II):mb ratios. Mb appeared to initially bind Cu(II) as a homodimer with a comparatively high copper affinity at Cu(II):mb ratios below 0.2, with a binding constant (K) greater than that of EDTA (log K = 18.8) and an approximate DeltaG degrees of -47 kcal/mol. At Cu(II):mb ratios between 0.2 and 0.45, the K dropped to (2.6 +/- 0.46) x 10(8) with a DeltaG degrees of -11.46 kcal/mol followed by another K of (1.40 +/- 0.21) x 10(6) and a DeltaG degrees of -8.38 kcal/mol at Cu(II):mb ratios of 0.45-0.85. The kinetic and spectral changes also suggested Cu(II) was initially coordinated to the 4-thiocarbonyl-5-hydroxy imidazolate (THI) and possibly Tyr, followed by reduction to Cu(I), and then coordination of Cu(I) to 4-hydroxy-5-thiocarbonyl imidazolate (HTI) resulting in the final coordination of Cu(I) by THI and HTI. The rate constant (k(obsI)) of binding of Cu(II) to THI exceeded that of the stopped flow apparatus that was used, i.e., >640 s(-)(1), whereas the coordination of copper to HTI showed a 6-8 ms lag time followed by a k(obsII) of 121 +/- 9 s(-)(1). Mb also solubilized and bound Cu(I) with a k(obsI) to THI of >640 s(-)(1), but with a slower rate constant to HTI (k(obsII) = 8.27 +/- 0.16 s(-)(1)), and appeared to initially bind Cu(I) as a monomer. 相似文献
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Molecular evolution of chloroplast DNA sequences 总被引:12,自引:1,他引:12
Comparative data on the evolution of chloroplast genes are reviewed. The
chloroplast genome has maintained a similar structural organization over
most plant taxa so far examined. Comparisons of nucleotide sequence
divergence among chloroplast genes reveals marked similarity across the
plant kingdom and beyond to the cyanobacteria (blue-green algae). Estimates
of rates of nucleotide substitution indicate a synonymous rate of 1.1 x
10(-9) substitutions per site per year. Noncoding regions also appear to be
constrained in their evolution, although addition/deletion events are
common. There have also been evolutionary changes in the distribution of
introns in chloroplast encoded genes. Relative to mammalian mitochondrial
DNA, the chloroplast genome evolves at a conservative rate.
相似文献
38.
Philip Dershwitz Nathan L. Bandow Junwon Yang Jeremy D. Semrau Marcus T. McEllistrem Rafael A. Heinze Matheus Fonseca Joshua C. Ledesma Jacob R. Jennett Ana M. DiSpirito Navjot S. Athwal Mark S. Hargrove Thomas A. Bobik Hans Zischka Alan A. DiSpirito 《Applied and environmental microbiology》2021,87(14)
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FOXOs support the metabolic requirements of normal and tumor cells by promoting IDH1 expression 下载免费PDF全文
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The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC. 相似文献