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排序方式: 共有407条查询结果,搜索用时 16 毫秒
91.
92.
Kwok B Yamauchi A Rajesan R Chan L Dhillon U Gao W Xu H Wang B Takahashi S Semple J Tamai I Nezu J Tsuji A Harper P Ito S 《American journal of physiology. Regulatory, integrative and comparative physiology》2006,290(3):R793-R802
The barrier function of the human mammary gland collapses if challenged with cationic drugs, causing their accumulation in milk. However, underlying molecular mechanisms are not well understood. To gain insight into the mechanism, we characterized transport of organic cations in the MCF12A human mammary gland epithelial cells, using carnitine and tetraethylammonium (TEA) as representative nutrient and xenobiotics probes, respectively. Our results show that the mammary gland cells express mRNA and proteins of human (h) novel organic cation transporters (OCTN) 1 and hOCTN2 (a Na+-dependent carnitine carrier with Na+-independent xenobiotics transport function), which belong to the solute carrier superfamily (SLC) of transporters. Other SLC OCTs such as hOCT1 and extraneuronal monoamine transporter (EMT)/hOCT3 are also expressed at mRNA levels, but hOCT2 was undetectable. We further showed mRNA expression of ATB0+ (an amino acid transporter with a Na+/Cl(-)-dependent carnitine transport activity), and Fly-like putative transporter 2/OCT6 (a splice variant of carnitine transporter 2: a testis-specific Na+-dependent carnitine transporter). TEA uptake was pH dependent. Carnitine uptake was dependent on Na+, and partly on Cl-, compatible with hOCTN2 and ATB0+ function. Modeling analyses predicted multiplicity of the uptake mechanisms with the high-affinity systems characterized by K(m) of 5.1 microM for carnitine and 1.6 mM for TEA, apparently similar to the reported hOCTN2 parameter for carnitine, and that of EMT/hOCT3 for TEA. Verapamil, cimetidine, carbamazepine, quinidine, and desipramine inhibited the carnitine uptake but required supratherapeutic concentrations, suggesting robustness of the carnitine uptake systems against xenobiotic challenge. Our findings suggest functional roles of a network of multiple SLC organic cation/nutrient transporters in human mammary gland drug transfer. 相似文献
93.
Rumbaut RE Bellera RV Randhawa JK Shrimpton CN Dasgupta SK Dong JF Burns AR 《American journal of physiology. Heart and circulatory physiology》2006,290(4):H1671-H1679
Endotoxemia promotes adhesive interactions between platelets and microvascular endothelium in vivo. We sought to determine whether endotoxin (lipopolysaccharide, LPS) modified platelet thrombus formation in mouse cremaster venules and whether Toll-like receptor 4 (TLR4) and neutrophils were involved in the response. Intravital videomicroscopy was performed in the cremaster microcirculation of pentobarbital-anesthetized mice; venular platelet thrombi were induced with a light/dye endothelial injury model. C57BL/6 mice treated with Escherichia coli endotoxin had enhanced rates of venular platelet thrombus formation: the time to microvessel occlusion was reduced by approximately 50% (P < 0.005) compared with saline-treated animals. Enhanced microvascular thrombosis was evident as early as 2 h after LPS administration. LPS had no effect on thrombosis in either of two mouse strains with altered TLR4 signaling (C57BL/10ScNJ or C3H/HeJ), whereas it enhanced thrombosis in the control strains (C57BL/10J and C3H/HeN). LPS also enhanced platelet adhesion to endothelium in the absence of light/dye injury. Platelet adhesion, but not enhanced thrombosis, was inhibited by depletion of circulating neutrophils. LPS failed to enhance platelet aggregation ex vivo and did not influence platelet P-selectin expression, a marker of platelet activation. These findings support the notion that endotoxemia promotes platelet thrombus formation independent of neutrophils and without enhancement of platelet aggregation, via a TLR4-dependent mechanism. 相似文献
94.
95.
Membrane proteins, owing to their highly hydrophobic nature, have always posed a daunting challenge to biochemists and structural biologists working on the characterization of these “naughty” proteins. Here we describe a problem that we encountered in the immunodetection of a hemagglutinin (HA) epitope-tagged membrane protein, Hgt1p (high-affinity glutathione transporter from the yeast Saccharomyces cerevisiae), for which little or no signal was observed on the blots with monoclonal antibody, on following the standard Western blot protocol. The introduction of a single step that involved posttransfer incubation of the blots with sodium dodecyl sulfate (SDS)/β-mercaptoethanol solution at 55 °C for 15 min enabled us to detect a strong, stable, and reproducible signal for the membrane protein. 相似文献
96.
97.
Mohammad Raish Varinderpal S Dhillon Arif Ahmad Mushtaq Ahmad Ansari Shahid Mudassar Mohammad Shahid Vineeta Batra Pawan Gupta Bhudev Chandra Das NK Shukla Syed Akhtar Husain 《Translational oncology》2009,2(4):264-270
BACKGROUND: Aberrant DNA methylation has been recognized in human breast carcinogenesis as a common molecular alteration associated with the loss of expression of a number of key regulatory genes. The present study was undertaken to determine whether methylation and expression of p16 and FHIT genes would correlate with the estrogen receptor (ER) and progesterone receptor (PR) status. METHODS: Methylation-specific polymerase chain reaction, messenger RNA (mRNA) expression analysis, immunohistochemistry, and Western blot analysis were performed to study the methylation of p16 and FHIT genes in 351 pairs of malignant/normal breast tissues. We examined the expression of ER and PR in those specimens by immunohistochemistry. Mutations of p16 and FHIT genes in tumors were detected by direct sequencing. RESULTS: The frequency of hypermethylation was 31.9% and 36.8% in p16 and FHIT genes, respectively, and showed significant harmony in concordant hypermethylation (P < .0001). In postmenopausal patients, methylation frequency in both genes is significantly higher in poorly and moderately differentiated tumors. Loss of protein expression of p16 and FHIT in 77 and 74 tumors, respectively, is associated with their methylation status in premenopausal women. CONCLUSION: We did not find any significant differences in tumor-related gene methylation patterns relevant to both ER and PR status of breast tumors. 相似文献
98.
Thilo Wegenast H. Friedrich Utz C. Friedrich H. Longin Hans Peter Maurer Baldev S. Dhillon Albrecht E. Melchinger 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(4):699-708
In hybrid maize (Zea mays L.) breeding, doubled haploids (DH) are increasingly replacing inbreds developed by recurrent selfing. Doubled haploids may
be developed directly from S0 plants in the parental cross or via S1 families. In both these breeding schemes, we examined 2 two-stage selecting strategies, i.e., considering or ignoring cross
and family structure while selection among and within parental crosses and S1 families. We examined the optimum allocation of resources to maximize the selection gain ΔG and the probability P(q) of identifying the q% best genotypes. Our specific objectives were to (1) determine the optimum number and size of crosses and S1 families, as well as the optimum number of test environments and (2) identify the superior selection strategy. Selection
was based on the evaluation of testcross progenies of (1) DH lines in both stages (DHTC) and (2) S1 families in the first stage and of DH lines within S1 families in the second stage (S1TC-DHTC) with uniform and variable sizes of crosses and S1 families. We developed and employed simulation programs for selection with variable sizes of crosses and S1 families within crosses. The breeding schemes and selection strategies showed similar relative efficiency for both optimization
criteria ΔG and P (0.1%). As compared with DHTC, S1TC-DHTC had larger ΔG and P (0.1%), but a higher standard deviation of ΔG. The superiority of S1TC-DHTC was increased when the selection was done among all DH lines ignoring their cross and family structure and using variable
sizes of crosses and S1 families. In DHTC, the best selection strategy was to ignore cross structures and use uniform size of crosses. 相似文献
99.
Tobias A. Schrag Jens Möhring Albrecht E. Melchinger Barbara Kusterer Baldev S. Dhillon Hans-Peter Piepho Matthias Frisch 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(2):451-461
The identification of superior hybrids is important for the success of a hybrid breeding program. However, field evaluation
of all possible crosses among inbred lines requires extremely large resources. Therefore, efforts have been made to predict
hybrid performance (HP) by using field data of related genotypes and molecular markers. In the present study, the main objective
was to assess the usefulness of pedigree information in combination with the covariance between general combining ability
(GCA) and per se performance of parental lines for HP prediction. In addition, we compared the prediction efficiency of AFLP
and SSR marker data, estimated marker effects separately for reciprocal allelic configurations (among heterotic groups) of
heterozygous marker loci in hybrids, and imputed missing AFLP marker data for marker-based HP prediction. Unbalanced field
data of 400 maize dent × flint hybrids from 9 factorials and of 79 inbred parents were subjected to joint analyses with mixed
linear models. The inbreds were genotyped with 910 AFLP and 256 SSR markers. Efficiency of prediction (R
2) was estimated by cross-validation for hybrids having no or one parent evaluated in testcrosses. Best linear unbiased prediction
of GCA and specific combining ability resulted in the highest efficiencies for HP prediction for both traits (R
2 = 0.6–0.9), if pedigree and line per se data were used. However, without such data, HP for grain yield was more efficiently
predicted using molecular markers. The additional modifications of the marker-based approaches had no clear effect. Our study
showed the high potential of joint analyses of hybrids and parental inbred lines for the prediction of performance of untested
hybrids. 相似文献
100.
High congruency of QTL positions for heterosis of grain yield in three crosses of maize 总被引:1,自引:0,他引:1
Chris C. Schön Baldev S. Dhillon H. Friedrich Utz Albrecht E. Melchinger 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,120(2):321-332
The genetic basis of heterosis in maize has been investigated in a number of studies but results have not been conclusive.
Here, we compare quantitative trait loci (QTL) mapping results for grain yield, grain moisture, and plant height from three
populations derived from crosses of the heterotic pattern Iowa Stiff Stalk Synthetic × Lancaster Sure Crop, investigated with
the Design III, and analyzed with advanced statistical methods specifically developed to examine the genetic basis of mid-parent
heterosis (MPH). In two populations, QTL analyses were conducted with a joint fit of linear transformations Z
1 (trait mean across pairs of backcross progenies) and Z
2 (half the trait difference between pairs of backcross progenies) to estimate augmented additive and augmented dominance effects
of each QTL, as well as their ratio. QTL results for the third population were obtained from the literature. For Z
2 of grain yield, congruency of QTL positions was high across populations, and a large proportion of the genetic variance (~70%)
was accounted for by QTL. This was not the case for Z
1 or the other two traits. Further, almost all congruent grain yield QTL were located in the same or an adjacent bin encompassing
the centromere. We conclude that different alleles have been fixed in each heterotic pool, which in combination with allele(s)
from the opposite heterotic pool lead to high MPH for grain yield. Their positive interactions very likely form the base line
for the superior performance of the heterotic pattern under study. 相似文献