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41.
Complete nucleotide sequences of bovine alpha S2- and beta-casein cDNAs: comparisons with related sequences in other species 总被引:2,自引:0,他引:2
Stewart AF; Bonsing J; Beattie CW; Shah F; Willis IM; Mackinlay AG 《Molecular biology and evolution》1987,4(3):231-241
The nucleotide sequences corresponding to bovine alpha S2- and beta- casein
mRNAs have been determined by cDNA analysis. Both sequences appear to be
complete at their 5' ends. The nucleotide sequence of alpha S2-casein, when
compared with the corresponding cavine A sequence, helps to define the
boundaries of a large amino acid repeat (approximately 80 residues) whereas
comparisons with the nucleotide sequences of rat gamma- and mouse
epsilon-casein mRNAs also reveal extensive sequence similarities. An
alignment of these four sequences shows that the divergence of their
translated regions has been characterized by the duplication and deletion
of discrete segments of sequence that probably correspond to exons. A high
degree of nucleotide substitution is also found when the four sequences are
compared, except for well-conserved leader-peptide and phosphorylation-site
sequences and, to a lesser extent, the 5'-untranslated regions. Similar
comparison of the bovine and rat beta-caseins shows that their divergence
has involved a high rate of nucleotide substitution but that no major
insertions or deletions of sequence have occurred. The several splice sites
that have veen defined in the rat beta-casein gene are likely to have been
conserved in the bovine. The contrasting evolutionary histories of the
alpha- and beta-casein coding sequences correlate with the distinctive
functions of these proteins in the casein micelle system in milk.
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43.
ABEL TRUJILLO-OCAMPO HYUN-WOO CHO AMANDA C. HERRMANN WILFREDO RUIZ-VAZQUEZ ANDREW B. THORNTON HONG HE DAN LI MARIAM A. QAZILBASH QING MA STEVEN A. PORCELLI ELIZABETH J. SHPALL JEFFREY MOLLDREM JIN S. IM 《Cytotherapy》2018,20(8):1089-1101
Background aims
CD1d-restricted invariant natural killer (iNK) T cells are rare regulatory T cells that may contribute to the immune-regulation in allogeneic stem cell transplantation (ASCT). Here, we sought to develop an effective strategy to expand human iNK T cells for use in cell therapy to prevent graft-versus-host disease (GVHD) in ASCT.Methods
Human iNK T cells were first enriched from peripheral blood mononuclear cells (PBMCs) using magnetic-activated cell sorting separation, then co-cultured with dendritic cells in the presence of agonist glycolipids, alpha-galactosylceramide, for 2 weeks.Results
The single antigenic stimulation reliably expanded iNK T cells to an average of 2.8?×?107 per 5?×?108 PBMCs in an average purity of 98.8% in 2 weeks (N?=?24). The expanded iNK T cells contained a significantly higher level of CD4+ and central memory phenotype (CD45RA?CD62L+) compared with freshly isolated iNK T cells, and maintained their ability to produce both Th-1 (interferon [IFN]γ and tumor necrosis factor [TNF]α) and Th-2 type cytokines (interleukin [IL]-4, IL-5 and IL-13) upon antigenic stimulation or stimulation with Phorbol 12-myristate 13-acetate/ionomycin. Interestingly, expanded iNK T cells were highly autoreactive and produced a Th-2 polarized cytokine production profile after being co-cultured with dendritic cells alone without exogenous agonist glycolipid antigen. Lastly, expanded iNK T cells suppressed conventional T-cell proliferation and ameliorated xenograft GVHD (hazard ratio, 0.1266; P < 0.0001).Conclusion
We have demonstrated a feasible approach for obtaining ex vivo expanded, highly enriched human iNK T cells for use in adoptive cell therapy to prevent GVHD in ASCT. 相似文献44.
Robin IM Dunbar 《BMC biology》2007,5(1):21-3
The claim that differences in brain size across primate species has mainly been driven by the demands of sociality (the "social
brain" hypothesis) is now widely accepted. Some of the evidence to support this comes from the fact that species that live
in large social groups have larger brains, and in particular larger neocortices. Lindenfors and colleagues (BMC Biology 5:20) add significantly to our appreciation of this process by showing that there are striking differences between the two
sexes in the social mechanisms and brain units involved. Female sociality (which is more affiliative) is related most closely
to neocortex volume, but male sociality (which is more competitive and combative) is more closely related to subcortical units
(notably those associated with emotional responses). Thus different brain units have responded to different selection pressures. 相似文献
45.
Dozmorov MG Yang Q Matwalli A Hurst RE Culkin DJ Kropp BP Lin HK 《Genomic Medicine》2007,1(3-4):139-146
5alpha-Androstane-3alpha,17beta-diol (3alpha-diol) is reduced from the potent androgen, 5alpha-dihydrotestosterone (5alpha-DHT), by reductive 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs) in the prostate. 3alpha-diol is recognized as a weak androgen with low affinity toward the androgen receptor (AR), but can be oxidized back to 5alpha-DHT. However, 3alpha-diol may have potent effects by activating cytoplasmic signaling pathways, stimulating AR-independent prostate cell growth, and, more importantly, providing a key signal for androgen-independent prostate cancer progression. A cancer-specific, cDNA-based membrane array was used to determine 3alpha-diol-activated pathways in regulating prostate cancer cell survival and/or proliferation. Several canonical pathways appeared to be affected by 3alpha-diol-regulated responses in LNCaP cells; among them are apoptosis signaling, PI3K/AKT signaling, and death receptor signaling pathways. Biological analysis confirmed that 3alpha-diol stimulates AKT activation; and the AKT pathway can be activated independent of the classical AR signaling. These observations sustained our previous observations that 3alpha-diol continues to support prostate cell survival and proliferation regardless the status of the AR. We provided the first systems biology approach to demonstrate that 3alpha-diol-activated cytoplasmic signaling pathways are important components of androgen-activated biological functions in human prostate cells. Based on the observations that levels of reductive 3alpha-HSD expression are significantly elevated in localized and advanced prostate cancer, 3alpha-diol may, therefore, play a critical role for the transition from androgen-dependent to androgen-independent prostate cancer in the presence of androgen deprivation. 相似文献
46.
Effect of self-association on the structural organization of partially folded proteins: inactivated actin 总被引:1,自引:0,他引:1
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IM Kuznetsova AG Biktashev SY Khaitlina KS Vassilenko KK Turoverov VN Uversky 《Biophysical journal》1999,77(5):2788-2800
The propensity to associate or aggregate is one of the characteristic properties of many nonnative proteins. The aggregation of proteins is responsible for a number of human diseases and is a significant problem in biotechnology. Despite this, little is currently known about the effect of self-association on the structural properties and conformational stability of partially folded protein molecules. G-actin is shown to form equilibrium unfolding intermediate in the vicinity of 1.5 M guanidinium chloride (GdmCl). Refolding from the GdmCl unfolded state is terminated at the stage of formation of the same intermediate state. An analogous form, known as inactivated actin, can be obtained by heat treatment, or at moderate urea concentration, or by the release of Ca(2+). In all cases actin forms specific associates comprising partially folded protein molecules. The structural properties and conformational stability of inactivated actin were studied over a wide range of protein concentrations, and it was established that the process of self-association is rather specific. We have also shown that inactivated actin, being denatured, is characterized by a relatively rigid microenvironment of aromatic residues and exhibits a considerable limitation in the internal mobility of tryptophans. This means that specific self-association can play an important structure-forming role for the partially folded protein molecules. 相似文献
47.
Jarvis JN Petty HR Tang Y Frank MB Tessier PA Dozmorov I Jiang K Kindzelski A Chen Y Cadwell C Turner M Szodoray P McGhee JL Centola M 《Arthritis research & therapy》2006,8(5):R154-14
Although strong epidemiologic evidence suggests an important role for adaptive immunity in the pathogenesis of polyarticular juvenile rheumatoid arthritis (JRA), there remain many aspects of the disease that suggest equally important contributions of the innate immune system. We used gene expression arrays and computer modeling to examine the function in neutrophils of 25 children with polyarticular JRA. Computer analysis identified 712 genes that were differentially expressed between patients and healthy controls. Computer-assisted analysis of the differentially expressed genes demonstrated functional connections linked to both interleukin (IL)-8- and interferon-gamma (IFN-gamma)-regulated processes. Of special note is that the gene expression fingerprint of children with active JRA remained essentially unchanged even after they had responded to therapy. This result differed markedly from our previously reported work, in which gene expression profiles in buffy coats of children with polyarticular JRA reverted to normal after disease control was achieved pharmacologically. These findings suggest that JRA neutrophils remain in an activated state even during disease quiescence. Computer modeling of array data further demonstrated disruption of gene regulatory networks in clusters of genes modulated by IFN-gamma and IL-8. These cytokines have previously been shown to independently regulate the frequency (IFN-gamma) and amplitude (IL-8) of the oscillations of key metabolites in neutrophils, including nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and superoxide ion. Using real-time, high-speed, single-cell photoimaging, we observed that 6/6 JRA patients displayed a characteristic defect in 12% to 23% of the neutrophils tested. Reagents known to induce only frequency fluctuations of NAD(P)H and superoxide ion induced both frequency and amplitude fluctuations in JRA neutrophils. This is a novel finding that was observed in children with both active (n = 4) and inactive (n = 2) JRA. A subpopulation of polyarticular JRA neutrophils are in a chronic, activated state, a state that persists when the disease is well controlled pharmacologically. Furthermore, polyarticular JRA neutrophils exhibit an intrinsic defect in the regulation of metabolic oscillations and superoxide ion production. Our data are consistent with the hypothesis that neutrophils play an essential role in the pathogenesis of polyarticular JRA. 相似文献
48.
Genome-scale microarray experiments for comparative analysis of gene expressions produce massive amounts of information. Traditional statistical approaches fail to achieve the required accuracy in sensitivity and specificity of the analysis. Since the problem can be resolved neither by increasing the number of replicates nor by manipulating thresholds, one needs a novel approach to the analysis. This article describes methods to improve the power of microarray analyses by defining internal standards to characterize features of the biological system being studied and the technological processes underlying the microarray experiments. Applying these methods, internal standards are identified and then the obtained parameters are used to define (i) genes that are distinct in their expression from background; (ii) genes that are differentially expressed; and finally (iii) genes that have similar dynamical behavior. 相似文献
49.
R V Petrov I M Dozmorov M O Kochetkova I S Nikolaeva 《Biulleten' eksperimental'no? biologii i meditsiny》1986,101(5):586-587
The interaction of lymphocytes from mouse lymph nodes with allogeneic stem cells was studied using exogenous colony formation inhibition test. Dual nature of the interaction was revealed: great amounts of lymphocytes inhibited, while small amounts stimulated colony formation. This dependence holds true for macro- and microcolonies as well as for erythrocyte and granuloid microcolonies in the bone marrow during fixation on day 8 and 11 after cell mixture transplantation. 相似文献
50.
Xu Z Potula HH Vallurupalli A Perry D Baker H Croker BP Dozmorov I Morel L 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(12):6673-6682
Sle2c1 is an NZM2410- and NZB-derived lupus susceptibility locus that induces an expansion of the B1a cell compartment. B1a cells have a repertoire enriched for autoreactivity, and an expansion of this B cell subset occurs in several mouse models of lupus. A combination of genetic mapping and candidate gene analysis presents Cdkn2c, a gene encoding for cyclin-dependent kinase inhibitor p18(INK4c) (p18), as the top candidate gene for inducing the Slec2c1-associated expansion of B1a cells. A novel single nucleotide polymorphism in the NZB allele of the Cdkn2c promoter is associated with a significantly reduced Cdkn2c expression in the splenic B cells and peritoneal cavity B1a cells from Sle2c1-carrying mice, which leads to a defective G1 cell cycle arrest in splenic B cells and increased proliferation of peritoneal cavity B1a cells. As the cell cycle is differentially regulated in B1a and B2 cells, these results suggest that Cdkn2c plays a critical role in B1a cell self-renewal and that its impaired expression leads to an accumulation of these cells with high autoreactive potential. 相似文献