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21.
The interaction between the T cell receptor and the major histocompatibility complex is one of the most important events in adaptive immunology. Although several different models for the activation process of the T cell via the T cell receptor have been proposed, it could not be shown that a structural mechanism, which discriminates between peptides of different immunogenicity levels, exists within the T cell receptor. In this study, we performed systematic molecular dynamics simulations of 172 closely related altered peptide ligands in the same T cell receptor/major histocompatibility complex system. Statistical evaluations yielded significant differences in the initial relaxation process between sets of peptides at four different immunogenicity levels. 相似文献
22.
G Cuce S Cetinkaya N Isitez S Kuccukturk ME Sozen S Kalkan 《Biotechnic & histochemistry》2016,91(2):122-127
Methylmethane sulfonate (MMS) is an alkylating agent that may react with DNA and damage it. We investigated histological changes and apoptosis caused by MMS and the effects of curcumin on MMS treated mouse kidneys. Twenty-four mice were divided into four equal groups: controls injected with saline, a group injected with 40 mg/kg MMS, a group injected with 40 mg/kg MMS and given 100 mg/kg curcumin by gavage, and a group given 100 mg/kg curcumin by gavage. MMS caused congestion and vacuole formation, and elevated the apoptotic index significantly, but had no other effect on kidney tissue. Curcumin improved the congestion and vacuole formation caused by MMS and decreased the apoptotic index. Curcumin administered with MMS appears to decrease the deleterious effects of MMS on the kidney. 相似文献
23.
24.
Gallala H Macheleidt O Doering T Schreiner V Sandhoff K 《European journal of cell biology》2004,83(11-12):667-679
During terminal differentiation of keratinocytes the expression of various proteins, which are required for the formation of the epidermal water barrier in the skin of land dwelling animals, is upregulated. Using a cell culture model for the differentiation of human keratinocytes and real-time PCR, we quantified the mRNA levels of several proteins involved in differentiation and ceramide metabolism. A calcium shift (1.1 mM CaCl2, 10 microM linoleic acid) for 8 days triggered an increase in mRNA levels of keratin 10 (75-fold), profilaggrin (55-fold), glucosylceramide synthase (40-fold), beta-glucocerebrosidase (30-fold), prosaposin (15-fold), acid sphingomyelinase (5-fold), and serine palmitoyltransferase (SPTLC2, 4-fold). However, mRNA levels of keratin 14 and acid ceramidase did not change significantly. On the other hand nitric oxide added at concentrations lower than 0.25mM stimulates proliferation of keratinocytes (Krischel et al., J. Invest. Dermatol. 111, 286-291, 1998). Accordingly, the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 0.2 mM) had no effect on the morphology of cultured keratinocytes, whereas in cultured human fibroblasts apoptosis was induced. The expression patterns obtained suggest that keratinocytes remain in a basal proliferative state, with a 3-fold increase in keratin 14 expression, a marked decrease in mRNA levels of differentiation markers and of most ceramide-metabolizing enzymes to negligible levels. The inhibitor of the NO synthase, N(G)-nitro-L-arginine-methyl ester (L-NAME, 10 mM), induced a transient increase in ceramide formation, followed by apoptosis in keratinocytes but not in fibroblasts. Both, SNAP and L-NAME, decreased the mRNA levels of all proteins involved in ceramide metabolism. 相似文献
25.
Heterogeneous perfusion is a consequence of uniform shear stress in optimized arterial tree models 总被引:1,自引:0,他引:1
Schreiner W Karch R Neumann M Neumann F Roedler SM Heinze G 《Journal of theoretical biology》2003,220(3):285-301
Using optimized computer models of arterial trees we demonstrate that flow heterogeneity is a necessary consequence of a uniform shear stress distribution. Model trees are generated and optimized under different modes of boundary conditions. In one mode flow is delivered to the tissue as homogeneously as possible. Although this primary goal can be achieved, resulting shear stresses between blood and the vessel walls show very large spread. In a second mode, models are optimized under the condition of uniform shear stress in all segments which in turn renders flow distribution heterogeneous. Both homogeneous perfusion and uniform shear stress are desirable goals in real arterial trees but each of these goals can only be approached at the expense of the other. While the present paper refers only to optimized models, we assume that this dual relation between the heterogeneities in flow and shear stress may represent a more general principle of vascular systems. 相似文献
26.
Functional convergence of response properties in the auditory thalamocortical system 总被引:10,自引:0,他引:10
One of the brain's fundamental tasks is to construct and transform representations of an animal's environment, yet few studies describe how individual neurons accomplish this. Our results from correlated pairs in the auditory thalamocortical system show that cortical excitatory receptive field regions can be directly inherited from thalamus, constructed from smaller inputs, and assembled by the cooperative activity of neuronal ensembles. The prevalence of functional thalamocortical connectivity is strictly governed by tonotopy, but connection strength is not. Finally, spectral and temporal modulation preferences in cortex may differ dramatically from the thalamic input. Our observations reveal a radical reconstruction of response properties from auditory thalamus to cortex, and illustrate how some properties are propagated with great fidelity while others are significantly transformed or generated intracortically. 相似文献
27.
Just W Baumstark A Hameister H Schreiner B Reisert I Hakhverdyan M Vogel W 《Cytogenetic and genome research》2002,96(1-4):146-153
Mammalian sex determination and gonad differentiation are the result of a complex interaction of fine-tuned spatial and temporal gene expression with threshold levels of individual genes. The male pathway is initiated by SRY. Some exceptional mammals determine male sex without the SRY gene and even without a Y chromosome. Ellobius lutescens in this report is one example of this "weird" species. We provide key data on the genomic level that there are no coarse differences in the genomes of male and female animals by comparative genomic hybridization. On the gene level we studied the gene Nr5a1 for the orphan nuclear receptor, steroidogenic factor SF-1, a central constituent for gonad differentiation and adrenal gland development. The Ellobius lutescens Nr5a1 gene was mapped to the proximal short arm of chromosome 2 by fluorescence in situ hybridization. In addition, we provide evidence by linkage analysis in two E. lutescens pedigrees that Nr5a1 is not the key male sex-determining gene in Ellobius lutescens. 相似文献
28.
Six to eight copies of a transgene integrated into mouse chromosome 15 resulting in a new transgene insertional mutant, Footless, presenting with malformations of the limbs, kidney, and soft palate. Homozygotes possess a unique asymmetric pattern of limb truncations. Posterior structures from the autopod and zeugopod of the hindlimbs are missing with left usually more severely affected than right. In contrast, anterior structures are missing from the right forelimbs. The left forelimb is usually normal except for the absence of the distal telephalanges and nails. These structures are absent on all formed digits. In situ hybridization assays examined the expression of Shh, dHand, Msx2, Fgf8, En1, and Lmx1b in mutant limb buds and indicated normal establishment of the anterior/posterior and dorsal/ventral axes of the developing limbs. However, dysmorphology of the apical ectodermal ridge was observed in the mutant limb buds. 相似文献
29.
Liu G Lu W Bremer S Hameister H Schreiner B Hughes M Heng HH 《Cytogenetics and cell genetics》2000,90(3-4):271-274
We have evaluated the mouse cell line WMP2 using both GTG-banding analysis and spectral karyotyping to verify the reliability of using this established cell line derived from WMP/WMP mice. The WMP cell lines contain easily identifiable metacentric fusion chromosomes and are used extensively for gene mapping. Because of karyotypical changes in the WMP1 cell line, WMP2 was examined. Our results demonstrate that WMP2 is stable during culture, and the karyotype is simple and easy to use. Based on the findings discussed in this paper, we recommend the use of the WMP2 cell line for future prospective gene mapping in the mouse. 相似文献
30.
Rod and cone photoreceptors project from the outer retinal surface into a
carbohydrate-rich interphotoreceptor matrix (IPM). Unique IPM
glycoconjugates are distributed around rods and cones. Wheat germ
agglutinin (WGA) strongly decorates the rod matrix domains and weakly
decorates the cone matrix domains. This study characterizes the major
WGA-binding glycoprotein in the human IPM, which we refer to as SPACR
(sialoprotein associated with cones and rods). SPACR, which has a molecular
weight of 147 kDa, was isolated and purified from the IPM by lectin
affinity chromatography. A polyclonal antibody to SPACR was prepared that
colocalizes in tissue preparations with WGA-binding domains in the IPM.
Sequential digestion of SPACR with N- and O- glycosidases results in a
systematic increase in electrophorectic mobility, indicating the presence
of both N- and O-linked glycoconjugates. Complete deglycosylation results
in a reduction in the relative molecular mass of SPACR by about 30%.
Analysis of lectin binding allowed us to identify some of the structural
characteristics of SPACR glycoconjugates. Treatment with neuraminidase
exposes Galbeta1- 3GalNAc disaccharide as indicated by positive peanut
agglutinin (PNA) staining, accompanied by the loss of WGA staining. Maackia
amurensis agglutinins (MAA-1 and MAA-2), specific for sialic acid in
alpha2-3 linkage to Gal, bind SPACR, while Sambucus nigra agglutinin (SNA),
specific for alpha2-6 linked sialic acid, does not, indicating that the
dominant glycoconjugate determinant on SPACR is the O-linked carbohydrate,
NeuAcalpha2-3Galbeta1-3GalNAc. The abundance of sialic acid in SPACR
suggests that this glycoprotein may contribute substantially to the
polyanionic nature of the IPM. The carbohydrate chains present on SPACR
could also provide sites for extensive crosslinking and participate in the
formation of the ordered IPM lattice that surrounds the elongate
photoreceptors projecting from the outer retinal surface.
相似文献