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Tandemly arrayed duplicate genes are prevalent. The maize A1-b haplotype is a tandem duplication that consists of the components, alpha and beta. The rate of meiotic unequal recombination at A1-b is ninefold higher when a homolog is present than when it is absent (i.e., hemizygote). When a sequence heterologous homolog is available, 94% of recombinants (264/281) are generated via recombination with the homolog rather than with the sister chromatid. In addition, 83% (220/264) of homolog recombination events involved alpha rather than beta. These results indicate that: (1) the homolog is the preferred template for unequal recombination and (2) pairing of the duplicated segments with the homolog does not occur randomly but instead favors a particular configuration. The choice of recombination template (i.e., homolog vs. sister chromatid) affects the distribution of recombination breakpoints within a1. Rates of unequal recombination at A1-b are similar to the rate of recombination between nonduplicated a1 alleles. Unequal recombination is therefore common and is likely to be responsible for the generation of genetic variability, even within inbred lines. 相似文献
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Marna Pippel Kristen Boyce Hariharan Venkatesan Victor K. Phuong Wen Yan Terrance D. Barrett Guy Lagaud Lina Li Magda F. Morton Clodagh Prendergast Xiaodong Wu Nigel P. Shankley Michael H. Rabinowitz 《Bioorganic & medicinal chemistry letters》2009,19(22):6376-6378
In the previous article we demonstrated how certain CCK2R-selective anthranilic amides could be structurally modified to afford high-affinity, selective CCK1R activity. We now describe our efforts at modulating and optimizing the CCK1R and CCK2R affinities aimed at producing compounds with good pharmacokinetics properties and in vivo efficacy in rat models of gastric acid and pancreatic amylase secretion. 相似文献
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Polymorphisms in the CD28/CTLA4/ICOS genes: role in malignant melanoma susceptibility and prognosis?
Marna G. Bouwhuis Andreas Gast Adina Figl Alexander M. M. Eggermont Kari Hemminki Dirk Schadendorf Rajiv Kumar 《Cancer immunology, immunotherapy : CII》2010,59(2):303-312
The appearance of vitiligo and spontaneous regression of the primary lesion in melanoma patients illustrate a relationship
between tumor immunity and autoimmunity. T lymphocytes play a major role both in tumor immunity and autoimmunity. CD28, Cytotoxic
T lymphocyte antigen 4 (CTLA4) and inducible costimulator (ICOS) molecules are important secondary signal molecules in the
T lymphocyte activation. Single nucleotide polymorphisms (SNPs) in the CD28/CTLA4/ICOS gene region were reported to be associated
with several autoimmune diseases including, type-1 diabetes, SLE, autoimmune thyroid diseases and celiac disease. In this
study, we investigated the association of SNPs in the CD28, CTLA4 and ICOS genes with the risk of melanoma. We also assessed
the prognostic effect of the different polymorphisms in melanoma patients. Twenty-four tagging SNPs across the three genes
and four additional SNPs were genotyped in a cohort of 763 German melanoma patients and 734 healthy German controls. Influence
on prognosis was determined in 587 melanoma cases belonging to stage I or II of the disease. In general, no differences in
genotype or allele frequencies were detected between melanoma patients and controls. However, the variant alleles for two
polymorphisms in the CD28 gene were differentially distributed in cases and controls. Similarly no association of any polymorphism
with prognosis, except for the rs3181098 polymorphism in the CD28 gene, was observed. In addition, individuals with AA genotype
for rs11571323 polymorphism in the ICOS gene showed reduced overall survival. However, keeping in view the correction for
multiple hypothesis testing our results suggest that the polymorphisms in the CD28, CTLA4 and ICOS genes at least do not modulate
risk of melanoma and nor do those influence the disease prognosis in the investigated population. 相似文献
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Expression of the Mucosal Homing Receptor α4β7 Correlates with the Ability of CD8+ Memory T Cells To Clear Rotavirus Infection
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Jason R. Ros Marna B. Williams Lusijah S. Rott Eugene C. Butcher Harry B. Greenberg 《Journal of virology》1998,72(1):726-730
The integrin α4β7 plays an important role in lymphocyte homing to mucosal lymphoid tissues and has been shown to define a subpopulation of memory T cells capable of homing to intestinal sites. Here we have used a well-characterized intestinal virus, murine rotavirus, to investigate whether memory/effector function for an intestinal pathogen is associated with α4β7 expression. α4β7hi memory phenotype (CD44hi), α4β7− memory phenotype, and presumptively naive (CD44lo) CD8+ T lymphocytes from rotavirus-infected mice were sorted and transferred into Rag-2 (T- and B-cell-deficient) recipients that were chronically infected with murine rotavirus. α4β7hi memory phenotype CD8+ cells were highly efficient at clearing rotavirus infection, α4β7− memory cells were inefficient or ineffective, depending on the cell numbers transferred, and CD44lo cells were completely unable to clear chronic rotavirus infection. These data demonstrate that functional memory for rotavirus resides primarily in memory phenotype cells that display the mucosal homing receptor α4β7. 相似文献
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Hsia AP Wen TJ Chen HD Liu Z Yandeau-Nelson MD Wei Y Guo L Schnable PS 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(2):218-225
Temperature gradient capillary electrophoresis (TGCE) can be used to distinguish heteroduplex from homoduplex DNA molecules and can thus be applied to the detection of various types of DNA polymorphisms. Unlike most single nucleotide polymorphism (SNP) detection technologies, TGCE can be used even in the absence of prior knowledge of the sequences of the underlying polymorphisms. TGCE is both sensitive and reliable in detecting SNPs, small InDel (insertion/deletion) polymorphisms (IDPs) and simple sequence repeats, and using this technique it is possible to detect a single SNP in amplicons of over 800 bp and 1-bp IDPs in amplicons of approximately 500 bp. Genotyping data obtained via TGCE are consistent with data obtained via gel-based detection technologies. For genetic mapping experiments, TGCE has a number of advantages over alternative heteroduplex-detection technologies such as celery endonuclease (CELI) and denaturing high-performance liquid chromatography (dHPLC). Multiplexing can increase TGCEs throughput to 12 markers on 94 recombinant inbreds per day. Given its ability to efficiently and reliably detect a variety of subtle DNA polymorphisms that occur at high frequency in genes, TGCE shows great promise for discovering polymorphisms and conducting genetic mapping and genotyping experiments.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
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Tubbs Andrew S. Gallagher Rebecca Perlis Michael L. Hale Lauren Branas Charles Barrett Marna Gehrels Jo-Ann Alfonso-Miller Pamela Grandner Michael A. 《Sleep and biological rhythms》2020,18(2):143-153
Sleep and Biological Rhythms - Sleep disturbances, such as short sleep duration and insomnia, are core features of depression. However, it is unclear if sleep duration and insomnia have an... 相似文献
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Michael A. Linden Gerald J. Sedgewick Marna Ericson 《The journal of histochemistry and cytochemistry》2015,63(4):233-243
Obtaining digital images of color brightfield microscopy is an important aspect of biomedical research and the clinical practice of diagnostic pathology. Although the field of digital pathology has had tremendous advances in whole-slide imaging systems, little effort has been directed toward standardizing color brightfield digital imaging to maintain image-to-image consistency and tonal linearity. Using a single camera and microscope to obtain digital images of three stains, we show that microscope and camera systems inherently produce image-to-image variation. Moreover, we demonstrate that post-processing with a widely used raster graphics editor software program does not completely correct for session-to-session inconsistency. We introduce a reliable method for creating consistent images with a hardware/software solution (ChromaCal™; Datacolor Inc., NJ) along with its features for creating color standardization, preserving linear tonal levels, providing automated white balancing and setting automated brightness to consistent levels. The resulting image consistency using this method will also streamline mean density and morphometry measurements, as images are easily segmented and single thresholds can be used. We suggest that this is a superior method for color brightfield imaging, which can be used for quantification and can be readily incorporated into workflows. 相似文献
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Emu B Luca D Offutt C Grogan JL Rojkovich B Williams MB Tang MT Xiao J Lee JH Davis JC 《Arthritis research & therapy》2012,14(1):R6-10