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991.
Distribution of CIAPIN1 in normal fetal and adult human tissues. 总被引:2,自引:0,他引:2
Zhiming Hao Xiaohua Li Taidong Qiao Jing Zhang Xiaodong Shao Daiming Fan 《The journal of histochemistry and cytochemistry》2006,54(4):417-426
CIAPIN1, a newly identified antiapoptotic molecule that plays an essential role in mouse definitive hematopoiesis, is considered a downstream effector of the receptor tyrosine kinase-Ras signaling pathway. Our previous studies have indicated that CIAPIN1 is involved in the development of multidrug resistance (MDR) in gastric cancer cells. However, the mechanism of CIAPIN1-mediated antiapoptosis and MDR has not been fully elucidated. To reveal the possible physiological role of CIAPIN1, we examined the expression and distribution of CIAPIN1 in fetal and adult human tissues using immunohistochemistry. We found that CIAPIN1 was ubiquitously distributed in fetal and adult tissues, and was localized in both the cytoplasm and the nucleus. The expression patterns of CIAPIN1 were similar in fetal and adult tissues, and was correlated with the previously described expression pattern of p21ras. These observations suggest that CIAPIN1 expression appears to be involved in cell differentiation, and that it might exert universal and possibly important physiological functions under the regulation of Ras in humans. 相似文献
992.
Vitamin C Pretreatment Attenuates Hypoxia-Induced Disturbance of Sodium Currents in Guinea Pig Ventricular Myocytes 总被引:5,自引:0,他引:5
As an important in vivo antioxidant, vitamin C is commonly used clinically to alleviate hypoxia-induced heart symptoms. To approach the protective
mechanisms of vitamin C on hearts during hypoxia, we investigated the electrophysiological effects of vitamin C (1 mM, pretreated before hypoxia) on Na+ currents (including transient and persistent Na+ currents) in guinea pig ventricular myocytes during hypoxia by the whole-cell and single-channel patch-clamp techniques.
Whole-cell recordings showed that the mean current density of I
NaT in the hypoxia group decreased from the control value of 40.2142 ± 1.7735 to 27.1663 ± 1.8441 pA/pF and current density of
I
NaP increased from 0.3987 ± 0.0474 to 1.1854 ± 01994 pA/pF (n = 9, P < 0.05 vs. control) at 15 min. However, when vitamin C was administered before hypoxia as pretreatment, I
NaT and I
NaP varied moderately (mean current density of I
NaT decreasing from 41.6038 ± 2.9762 to 34.6341 ± 1.9651 pA/pF and current density of I
NaP increasing from 0.3843 ± 0.0636 to 0.6734 ± 0.1057 pA/pF; n = 9, P < 0.05 vs. hypoxia group). Single-channel recordings (cell-patched) showed that the mean open probability and open time of I
NaP increased significantly in both groups at hypoxia 15 min. However, the increased current values of the hypoxia group were
still marked at hypoxia 15 min (n = 9, P < 0.05 vs. vitamin C + hypoxia group). Our results indicate that vitamin C can attenuate the disturbed effects of hypoxia on Na+ currents (I
NaT and I
NaP) of cardiac myocytes in guinea pigs effectively. 相似文献
993.
This report presents a new and simple methodology for the synthesis of multicomponent peptide vaccines, named the peptide crosslinked micelles (PCMs). The PCMs are core shell micelles designed to deliver peptide antigens and immunostimulatory DNA to antigen-presenting cells (APCs). They are composed of immunostimulatory DNA, peptide antigen, and a thiopyridal derived poly(ethylene glycol)-polylysine block copolymer. The peptide antigen acts as a crosslinker in the PCM strategy, which allows the peptide antigen to be efficiently encapsulated into the PCMs and also stabilizes them against degradation by serum components. Cell culture studies demonstrated that the PCMs greatly enhance the uptake of peptide antigens into human dendritic cells. 相似文献
994.
Cyclin-dependent kinase-5 (Cdk5) is required for neuronal survival, but its targets in the apoptotic pathways remain unknown. Here, we show that Cdk5 kinase activity prevents neuronal apoptosis through the upregulation of Bcl-2. Treatment of SH-SY5Y cells with retinoid acid (RA) and brain-derived neurotrophic factor (BDNF) generates differentiated neuron-like cells. DNA damage triggers apoptosis in the undifferentiated cells through mitochondrial pathway; however, RA/BDNF treatment results in Bcl-2 upregulation and inhibition of the mitochondrial pathway in the differentiated cells. RA/BDNF treatment activates Cdk5-mediated PI3K/Akt and ERK pathways. Inhibition of Cdk5 inhibits PI3K/Akt and ERK phosphorylation and Bcl-2 expression, and thus sensitizes the differentiated cells to DNA-damage. Inhibition of ERK, but not PI3K/Akt, abrogates Cdk5-medidated Bcl-2 upregulation and the protection of the differentiated cells. This study suggests that ERK-mediated Bcl-2 upregulation contributes to BDNF-induced Cdk5-mediated neuronal survival. 相似文献
995.
MOTIVATION: With the development of DNA microarray technology, scientists can now measure the expression levels of thousands of genes simultaneously in one single experiment. One current difficulty in interpreting microarray data comes from their innate nature of 'high-dimensional low sample size'. Therefore, robust and accurate gene selection methods are required to identify differentially expressed group of genes across different samples, e.g. between cancerous and normal cells. Successful gene selection will help to classify different cancer types, lead to a better understanding of genetic signatures in cancers and improve treatment strategies. Although gene selection and cancer classification are two closely related problems, most existing approaches handle them separately by selecting genes prior to classification. We provide a unified procedure for simultaneous gene selection and cancer classification, achieving high accuracy in both aspects. RESULTS: In this paper we develop a novel type of regularization in support vector machines (SVMs) to identify important genes for cancer classification. A special nonconvex penalty, called the smoothly clipped absolute deviation penalty, is imposed on the hinge loss function in the SVM. By systematically thresholding small estimates to zeros, the new procedure eliminates redundant genes automatically and yields a compact and accurate classifier. A successive quadratic algorithm is proposed to convert the non-differentiable and non-convex optimization problem into easily solved linear equation systems. The method is applied to two real datasets and has produced very promising results. AVAILABILITY: MATLAB codes are available upon request from the authors. 相似文献
996.
Genetic Diversity and Core Collection Evaluations in Common Wheat Germplasm from the Northwestern Spring Wheat Region in China 总被引:6,自引:0,他引:6
C. Y. Hao X. Y. Zhang L. F. Wang Y. S. Dong X. W. Shang J. Z. Jia 《Molecular breeding : new strategies in plant improvement》2006,17(1):69-77
Fluorescence microsatellite markers were employed to reveal genetic diversity of 340 wheat accessions consisting of 229 landraces
and 111 modern varieties from the Northwest Spring Wheat Region in China. The 340 accessions were chosen as candidate core
collections for wheat germplasm in this region. A core collection representing the genetic diversity of these accessions was
identified based on a cluster dendrogram of 78 SSR loci. A total of 967 alleles were detected with a mean of 13.6 alleles
(5–32) per locus. Mean PIC was 0.64, ranged from 0.05 to 0.91. All loci were distributed relatively evenly in the A, B and
D wheat genomes. Mean genetic richness of A, B and D genomes for both landraces and modern varieties was B > A > D. However,
mean genetic diversity indices of landraces changed to B > D > A. As a whole, genetic diversity of the landraces was considerably
higher than that of the modern varieties. The big difference of genetic diversity indices in the three genomes suggested that
breeding has exerted greater selection pressure in the D than the A or B genomes in this region. Changes of allelic proportions
represented in the proposed core collection at different sampling scales suggested that the sampling percentage of the core
collection in the Northwest Spring Wheat Region should be greater than 4% of the base collection to ensure that more than
70% of the variation is represented by the core collection.
Electronic supplementary material Electronic supplementary material is available for this article at
and accessible for authorised users. 相似文献
997.
Enhanced somatic embryogenesis and plant regeneration have been obtained using young leaf bases of naked oat (Avena nuda) as explants by including salicylic acid (SA) and carrot embryogenic callus extracts (CECE) in media. A 5- and 4-fold improvement
was achieved in somatic embryogenesis and plant regeneration on the corresponding media supplemented with 0.5 mM SA and CECE
as compared to control, respectively. Some physiological and biochemical changes were assayed in both embryogenic callus (EC)
and non-embryogenic callus (NEC). The results indicated that superoxide dismutase activity was stimulated and catalases and
ascorbate peroxidase activities were inhibited, while the O2
- (superoxide anion) content was reduced and the hydrogen peroxide level was promoted in EC compared with NEC. Reduced malondialdehyde
content and relative electrolyte leakage were also detected in EC. 相似文献
998.
Application of "oxygen uptake rate-amino acids" associated mode in controlled-fed perfusion culture 总被引:1,自引:0,他引:1
Controlled-fed perfusion, a new operation mode, which combines the advantages of fed-batch and perfusion, has been reported to enhance monoclonal antibody productivity. The aim of the present study was to further enrich this mode by an "oxygen uptake rate-amino acids (OUR-AA)" strategy in which the feeding of amino acids was controlled according to the variation of OUR during perfusion. And the effects of this strategy on bioreactor productivity and product quality were evaluated. Experimental results indicated that by using this "OUR-AA" approach in controlled-fed perfusion mode a high viable cell density of more than 1.9 x 10(7)cells/ml was achieved and the productivity of mAb reached 325 mg/l/d, which was significantly increased by nearly twofold over those of the perfusion and fed-batch process. The residual concentrations of selected amino acids were controlled at a relative steady level by OUR during the culture. The immunoreactivity and the purity of the antibody were well preserved as the culture process was evolving from flask to the controlled-fed perfusion mode. The primary application of "OUR-AA" approach in controlled-fed perfusion mode may present a novel control strategy to enhance the culture performance and to display the potential of this approach in automatic control field. 相似文献
999.
The most commonly occurring sialic acid Neu5Ac (N-acetylneuraminic acid) and its deaminated form, KDN (2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid), participate in many biological functions. The human Neu5Ac-9-P (Neu5Ac 9-phosphate) synthase has the unique ability to catalyse the synthesis of not only Neu5Ac-9-P but also KDN-9-P (KDN 9-phosphate). Both reactions are catalysed by the mechanism of aldol condensation of PEP (phosphoenolpyruvate) with sugar substrates, ManNAc-6-P (N-acetylmannosamine 6-phosphate) or Man-6-P (mannose 6-phosphate). Mouse and putative rat Neu5Ac-9-P synthases, however, do not show KDN-9-P synthase activity, despite sharing high sequence identity (>95%) with the human enzyme. Here, we demonstrate that a single mutation, M42T, in human Neu5Ac-9-P synthase can abolish the KDN-9-P synthase activity completely without compromising the Neu5Ac-9-P synthase activity. Saturation mutagenesis of Met42 of the human Neu5Ac-9-P synthase showed that the substitution with all amino acids except leucine retains only the Neu5Ac-9-P synthase activity at levels comparable with the wild-type enzyme. The M42L mutant, like the wild-type enzyme, showed the additional KDN-9-P synthase activity. In the homology model of human Neu5Ac-9-P synthase, Met42 is located 22 A (1 A=0.1 nm) away from the substrate-binding site and the impact of this distant residue on the enzyme functions is discussed. 相似文献
1000.
The R-Ras GTPase mediates cross talk between estrogen and insulin signaling in breast cancer cells 下载免费PDF全文
The signaling cascades activated by insulin and IGF-1 contribute to the control of multiple cellular functions, including glucose metabolism and cell proliferation. In most cases these effects are mediated, at least in part, by insulin receptor substrates (IRS), one of which is insulin receptor substrate 1 (IRS-1). R-Ras is a member of the Ras family of GTPases and is involved in a variety of biological processes, including integrin activation, cell migration, and control of cell proliferation. Here we demonstrate that both R-Ras and BCAR3, a regulator of R-Ras activity that has been implicated in breast cancer, regulate the level of IRS-1 protein in estrogen-dependent MCF-7 and ZR75 breast cancer cells. In particular, expression of a constitutively activated R-Ras mutant, R-Ras38V, or of BCAR3 accelerates the degradation of IRS-1, leading to the impairment of signaling through insulin but not epidermal growth factor receptors. Moreover, knockdown of endogenous R-Ras levels in MCF-7 cells inhibits IRS-1 degradation induced by estrogen signaling blockade but not by long-term insulin treatment. Consistent with these results, both R-Ras38V expression and estrogen signaling blockade lead to the degradation of IRS-1, at least in part, through calpain activity. These findings show that R-Ras activity mediates inhibition of insulin signaling associated with suppression of estrogen action, implicating this GTPase in a growth-inhibitory mechanism associated with antiestrogen treatment of breast cancer. 相似文献