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Eike MC Olsson M Undlien DE Dahl-Jørgensen K Joner G Rønningen KS Thorsby E Lie BA 《Genes and immunity》2009,10(2):141-150
The main genetic predisposition to type 1 diabetes (T1D) is known to be conferred by the HLA-DRB1, -DQA1 and -DQB1 genes in the major histocompatibility complex (MHC). Other genetic factors within this complex are known to contribute, but their identity has often been controversial. This picture is shared with several other autoimmune diseases (AIDs). Moreover, as common genetic factors are known to exist between AIDs, associations reported with other AIDs may also be involved in T1D. In this study, we have used these observations in a candidate gene approach to look for additional MHC risk factors in T1D. Using complementary conditional methods (involving conditional logistic regression and family-based haplotype tests) and analyses of linkage disequilibrium (LD) patterns, we confirmed association for alleles of the HLA-A and HLA-B genes and found preliminary evidence for a novel association of a single-nucleotide polymorphism (rs2259571) in the AIF1 gene, independent of the DRB1-DQA1-DQB1 genes and of each other. However, no evidence of independent associations for a number of previously suggested candidate polymorphisms was detected. Our results illustrate the importance of a comprehensive adjustment for LD effects when performing association studies in this complex. 相似文献
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NADPH diaphorase-positive dendritic profiles in rat thymus are discrete from autofluorescent cells, immunoreactive for inducible nitric oxide synthase, and show strain-specific abundance differences.
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Predisposition to autoimmune disorder in Lewis rats has been associated with abnormal hypothalamic regulation of circulating steroids, leading to inadequate suppression of T helper 1 (Th1) cell-mediated inflammatory reactions. In addition, autoimmune syndromes can be triggered within formerly resistant animals, following damage to the negative selection process of the thymus. A contribution to the autoimmune-susceptible phenotype may therefore derive from the status of thymic tolerance. One mechanism of intrathymic negative selection may involve nitric oxide. Because inducible nitric oxide synthase (iNOS) is known to be inhibitable by steroids, its expression might be different within strains having neuroendocrine disturbance. We report on a study to compare intrathymic iNOS expression in autoimmune-prone Lewis rats with other resistant strains. Interdigitating cells (IDC), darkly stained for diaphorase, were confirmed as immunoreactive for iNOS. They were located towards the medullary side of an accumulation of unstained, but autofluorescent cells (presumed to be macrophages) that circumscribes the corticomedullary zone. The role of iNOS+ IDC in the apoptotic deletion of T cells has been suggested by other studies. Despite the blunted steroidal condition reported for Lewis, nitrergic cell abundance was shown, by quantitative analysis of histochemical stain, to be on average approximately twofold lower compared with resistant strains (Fischer and Sprague-Dawley). This trend was evident in males and females, and confirmed by independent observers. We hypothesize that an intrathymic, iNOS-dependent mechanism may be important for the suppression of potentially autoreactive T-cell clones. 相似文献
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The Defense Style Questionnaire-40 is a 40 item short form of the 88 item Defense Style Questionnaire. A cross-cultural comparison was made between a sample of 635 Canadian university students and an Australian sample of 388 subjects reported by Andrews, Singh, and Bond. Differences between the two samples were noted for several of the defense scales. These may be a reflection of differential socialization patterns in coping with stress for the two countries. Gender and age comparisons were made for the 20 defense scales. Some interesting differences were noted for gender on the suppression, pseudoaltruism, and isolation scales. The internal structure of defense styles was also found to have similarities and differences for males and females with the DSQ-40. © 1998 John Wiley & Sons, Inc. J Clin Psychol 54: 67–75, 1998. 相似文献
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Alan B. Zonderman 《Behavior genetics》1986,16(1):11-24
To honor the retirement of Steven G. Vandenberg, his contributions to multivariate behavioral genetics are reviewed. During Professor Vandenberg's prolific career, he made substantial contributions to three general areas: twin research, family studies, and research on individual differences. In the area of twin research, two large-scale studies, the Hereditary Abilities Study and the Louisville Twin Study, are reviewed. His contributions to the analysis of twin data, with particular reference to the canonical generalization of Bartlett'sF ratio, are also noted. In the area of family studies, Professor Vandenberg was principal or coprincipal investigator of the Boulder Family Study, the Hawaii Family Study of Cognition, the Colorado Adoption Project, and a twin-family study of smoking behavior; his papers on ethnic comparisons, assortative marriage, and kinship analyses are reviewed. In his research on individual differences, Professor Vandenberg conducted studies of the cross-ethnic factorial invariance of primary mental abilities in Chinese and South American students and took an early interest in automated methods for factor analysis. Over the course of his career, Professor Vandenberg has made a variety of tangible and intangible contributions to behavioral genetics, and his personal humility and scientific outlook have provided an important role model for his colleagues and students. 相似文献
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Biased distribution of inverted and direct Alus in the human genome: implications for insertion, exclusion, and genome stability 总被引:6,自引:1,他引:5
Alu sequences, the most abundant class of large dispersed DNA repeats in human chromosomes, contribute to human genome dynamics. Recently we reported that long inverted repeats, including human Alus, can be strong initiators of genetic change in yeast. We proposed that the potential for interactions between adjacent, closely related Alus would influence their stability and this would be reflected in their distribution. We have undertaken an extensive computational analysis of all Alus (the database is at http://dir.niehs.nih.gov/ALU) to better understand their distribution and circumstances under which Alu sequences might affect genome stability. Alus separated by <650 bp were categorized according to orientation, length of regions sharing high sequence identity, distance between highly identical regions, and extent of sequence identity. Nearly 50% of all Alu pairs have long alignable regions (>275 bp), corresponding to nearly full-length Alus, regardless of orientation. There are dramatic differences in the distributions and character of Alu pairs with closely spaced, nearly identical regions. For Alu pairs that are directly repetitive, approximately 30% have highly identical regions separated by <20 bp, but only when the alignments correspond to near full-size or half-size Alus. The opposite is found for the distribution of inverted repeats: Alu pairs with aligned regions separated by <20 bp are rare. Furthermore, closely spaced direct and inverted Alus differ in their truncation patterns, suggesting differences in the mechanisms of insertion. At larger distances, the direct and inverted Alu pairs have similar distributions. We propose that sequence identity, orientation, and distance are important factors determining insertion of adjacent Alus, the frequency and spectrum of Alu-associated changes in the genome, and the contribution of Alu pairs to genome instability. Based on results in model systems and the present analysis, closely spaced inverted Alu pairs with long regions of alignment are likely at-risk motifs (ARMs) for genome instability. 相似文献
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The chloroplast trnP-trnW-petG gene cluster has been identified in the mitochondrial DNA (mtDNA) of sugar beet (Beta vulgaris). The chloroplast-derived trnW gene is transcribed in the mitochondria; the other two genes, however, do not seem to be transcribed. This gene cluster is also present in the mitochondrial genomes of two wild Beta species, B. trigyna and B. webbiana. Sugar beet and the two wild relatives share 100% sequence identity in the coding regions of both the mitochondrial trnP and trnW genes. On the other hand, the petG genes from the wild Beta mtDNAs were found to be disrupted either by a 5-bp duplication (B. trigyna) or by a deletion of the 5 region (B. webbiana). A data-base search revealed that a conserved sequence of 60 bp is present in the trnP-trnW intergenic region of the mitochondrial genomes of the three Beta species as well as in other higher plants, including wheat and maize, and that the conserved sequence is absent from the chloroplast counterpart. Our results thus favour the hypothesis of a monophyletic origin of the trnP-trnW-petG cluster found in the plant mitochondrial genomes examined. 相似文献
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A. D. Durnev N. V. Guseva T. G. Sazontova G. N. Pleskovskaya S. B. Seredenin 《Bulletin of experimental biology and medicine》1995,120(4):1021-1023
Interstrain genotypic, sex, and age differences in the clastogenic action of cyclophosphamide in various doses are established
for C57B1/6, MRL/1, and BALB/c mice.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N
o
, pp. 387–390, October, 1995 相似文献
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Since 1988 malaria epidemics have occurred in multiple sites in western Kenya highlands. Climatic variability has been associated with some of the recent epidemics. We examined influences of climatic factors on the distribution and abundance of three malaria vector species, Anopheles gambiae, Anopheles arabiensis, and Anopheles funestus in western Kenya and in the Great Rift Valley. Mosquito samples were collected from the lowland and highland areas with various climatic conditions. The three vector species were abundant in the lower part of western Kenya. An. arabiensis was not found in the areas above 1,400 m elevation in western Kenya Although An. gambiae and An. funestus were found in the sites above 1,700 m in western Kenya, their densities were < 1 per house. In the Great Rift Valley, An. gambiae was not recorded. An. funestus was more widely distributed than the other two species. A stepwise multiple regression analysis found that moisture index was the most important variable in shaping species composition of the An. gambiae complex. Relative abundance of An. gambiae was positively associated with moisture index, suggesting that An. gambiae is more adapted to moist climate. Seasonal differences in species composition were significant in western Kenya, and the proportion of An. funestus was higher in the dry season than the rainy season. Influence of temperature on vector density was significant for all three species. These results imply that climate changes alter the distribution and abundance of malaria vectors in future. 相似文献
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Stem/progenitor cells are promising candidates for the regeneration of parenchyma in acute and chronic renal failure. After an implantation stem/progenitor cells must migrate through the interstitial space to concentrate at the site of damage. However, information is lacking to what extent the interstitial interface is influencing the development of stem/progenitor cells into nephron structures. In consequence, tubule regeneration within an artificial polyester interstitium was analyzed by electron microscopy in comparison with the interstitial interface of matured tubules and the interstitium within the renal stem/progenitor cell niche. The experiments demonstrate that fixation of specimens with glutaraldehyde (GA) is leading in all cases to inconspicuously looking interstitial interfaces. In contrast, fixation of regenerating tubules in GA containing ruthenium red and tannic acid shows a dense network of fibers lining along the basal lamina. In contrast, matured tubules reveal after ruthenium red label an extremely thickened basal lamina, while only a punctate pattern is obtained after tannic acid treatment. Finally, within the renal stem/progenitor cell niche ruthenium red and tannic acid label reveals large amounts of extracellular matrix spanning through the interstitium. Thus, fixation of tissue in GA containing ruthenium red and tannic acid exhibits an unexpectedly regional heterogeneity of the renal interstitial interface. This fact has to be considered for an optimal therapeutic repair of parenchyma, since contacts between stem/progenitor cells with the interstitial interface influence further development. 相似文献
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我们对采用PCR和聚丙烯酰胺凝胶电泳鉴别出的37例DNA完全来自父方的遗传学完全性葡萄胎(g-CHM)进行基因组中CTTtriplex系统各基因座位(CSF1PO、TPOX和TH01)等位基因分布的分析,并初步研究了这些等位基因分布与临床预后的关系。结果显示,在37例g-CHM中,CSF1PO座位中3个等位基因(11,12和14)和TPOX座位中的1个等位基因(11)的出现率与它们在北京地区人群中的基因频率差异显著;g-CHM中CSF1PO、TPOX和TH01基因座位杂合度显著低于北京地区人群的杂合度(P值均远小于0.01);在23例良性g-CHM和10例侵袭性g-CHM中:CSF1PO座位的等位基因10、11在良性中的出现率高于在侵袭性g-CHM中(P=0.026148),等位基因12在良性中的出现率低于在侵袭性g-CHM中(P=0.023879);TPOX座位的等位基因8在良性中的出现率高于在侵袭性g-CHM中(P=0.004322),而等位基因11在良性中的出现率低于其在侵袭性g-CHM中(P=0.008671)。上述结果提示,葡萄胎基因组中存在某些等位基因分布与在人群中的分布不同,而且葡萄胎是否具有侵袭性也和某些等位基因的出现率过高或过低有相关性,这些与侵袭性有关的等位基因可能成为预测葡萄胎是否具有侵袭性的标志物。 相似文献
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Qin-Qin Pan Su Fan Xiao-Yan Wang Meng Pan Xing Zhao Xiao-Yu Zhou Cheng-Ya Wang Jie Shen 《Human immunology》2011
We investigated the human leukocyte antigen (HLA)-A, -B, and -DRB1 allele frequencies, the A–B–DRB1, A–B, B–DRB1, and A–DRB1 haplotype frequencies, and the characteristics of linkage disequilibrium between 2 loci in high resolution based on 167 unrelated families from Jiangsu Province, China. A total of 26 alleles at the A locus, 55 alleles at the B locus, and 34 alleles at the DRB1 locus were reported in this study. The top 5 most frequent HLA alleles at the HLA-A, -B, and -DRB1 loci, respectively, were A*11:01, A*24:02, A*02:01, A*33:03, A*30:01; B*13:02, B*40:01 B*46:01, B*58:01, B*54:01; DRB1*09:01, DRB1*07:01, DRB1*12:02, DRB1*15:01, and DRB1*08:03. Several haplotypes with high frequencies were deduced in this study. The top 3 most common A–B–DRB1 haplotypes observed were A*30:01–B*13:02–DRB1*07:01, A*33:03–B*58:01–DRB1*03:01, and A*02:07–B*46:01–DRB1*09:01. The top 3 most common A–B haplotypes were A*30:01–B*13:02, A*33:03–B*58:01, and A*02:07–B*46:01. The top 4 most common A–DRB1 haplotypes were A*30:01–DRB1*07:01, A*33:03–DRB1*13:02, A*24:02–DRB1*09:01, and A*33:03–DRB1*03:01. Finally, the top 3 most common B–DRB1 haplotypes were B*13:02–DRB1*07:01, B*46:01–DRB1*09:01, and B*58:01–DRB1*03:01. From the linkage disequilibrium calculation, the most prominent associations were A*30:01–B*13:02, B*13:02–DRB1*07:01, and A*01:03–DRB1*01:02. These allele and haplotype frequencies could be useful for finding the best matched donors for patients in the China Marrow Donor Program Jiangsu Branch. 相似文献
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Inoculation of live Escherichia coli into tsetse flies, Glossina morsitans morsitans, stimulated a higher antibacterial immune response in females than in males. It increased with age in females from emergence to approximately 2 weeks and thereafter declined. In males, there was also a significant decrease in immune response with aging. Inoculation of killed bacteria failed to stimulate antibacterial activity but stimulated a lysozyme response which was weaker than that stimulated by live bacteria. No antibacterial activity was present in the hemolymph of larvae from immunized pregnant tsetse. Inoculation of live Trypanosoma brucei brucei and T. congolense failed to induce production of antibacterial activity and lysozyme. Furthermore, tsetse inoculated with or naturally infected with T. b. brucei and T. congolense failed to show any evidence of immunosuppression when challenged with live E. coli. Various species of live bacteria stimulated different levels of antibacterial factors, with Enterobacter cloacae stimulating the highest level of antibacterial activity and E. coli the highest level of lysozyme. Saline in which certain species of bacteria and T. b. brucei were incubated inactivated tsetse immune hemolymph. 相似文献
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IC McManus Andrew T Elder Andre de Champlain Jane E Dacre Jennifer Mollon Liliana Chis 《BMC medicine》2008,6(1):5
Background
The UK General Medical Council has emphasized the lack of evidence on whether graduates from different UK medical schools perform differently in their clinical careers. Here we assess the performance of UK graduates who have taken MRCP(UK) Part 1 and Part 2, which are multiple-choice assessments, and PACES, an assessment using real and simulated patients of clinical examination skills and communication skills, and we explore the reasons for the differences between medical schools. 相似文献18.
HLA-DQA1, -DQB1 and -DRB1 genotyping in Japanese pemphigus vulgaris patients by the PCR-RFLP method 总被引:8,自引:0,他引:8
Hironori Niizeki Hidetoshi Inoko Nobuhisa Mizuki Nobuko Inamoto Kyoko Watababe Takashi Hashimoto Takeji Nishikawa 《Tissue antigens》1994,44(4):248-251
Abstract: We performed HLA-DQA1, -DQB1 and -DRB1 genotyping using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method for 32 Japanese pemphigus vulgaris (PV) patients. There was a significant association of either DQB1*0503 or DRB1*1405 with PV, and a negative association of either DQA1*0103 or DQB1*0601 with PV was found. Since the DQB1*0503+ patients had various DR14-related alleles, we concluded that the association with DQB1 is primary and that the association with DRB1 is simply due to linkage disequilibrium between the DQ and DR genes. These results may indicate that specific HLA class II antigens confer the susceptibility to PV among Japanese. 相似文献
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Gustavo C. S. Kuhn Fabio M. Sene Orlando Moreira-Filho Trude Schwarzacher John S. Heslop-Harrison 《Chromosome research》2008,16(2):307-324
We aimed to study patterns of variation and factors influencing the evolutionary dynamics of a satellite DNA, pBuM, in all
seven Drosophila species from the buzzatii cluster (repleta group). We analyzed 117 alpha pBuM-1 (monomer length 190 bp) and 119 composite alpha/beta (370 bp) pBuM-2 repeats and determined the chromosome location and long-range organization on DNA fibers of major sequence
variants. Such combined methodologies in the study of satDNAs have been used in very few organisms. In most species, concerted
evolution is linked to high copy number of pBuM repeats. Species presenting low-abundance and scattered distributed pBuM repeats
did not undergo concerted evolution and maintained part of the ancestral inter-repeat variability. The alpha and alpha/beta repeats colocalized in heterochromatic regions and were distributed on multiple chromosomes, with notable differences between
species. High-resolution FISH revealed array sizes of a few kilobases to over 0.7 Mb and mutual arrangements of alpha and alpha/beta repeats along the same DNA fibers, but with considerable changes in the amount of each variant across species. From sequence,
chromosomal and phylogenetic data, we could infer that homogenization and amplification events involved both new and ancestral
pBuM variants. Altogether, the data on the structure and organization of the pBuM satDNA give insights into genome evolution
including mechanisms that contribute to concerted evolution and diversification.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. 总被引:7,自引:0,他引:7
Elizabeth D Hay 《Developmental dynamics》2005,233(3):706-720
This review centers on the role of the mesenchymal cell in development. The creation of this cell is a remarkable process, one where a tightly knit, impervious epithelium suddenly extends filopodia from its basal surface and gives rise to migrating cells. The ensuing process of epithelial-mesenchymal transformation (EMT) creates the mechanism that makes it possible for the mesenchymal cell to become mobile, so as to leave the epithelium and move through the extracellular matrix. EMT is now recognized as a very important mechanism for the remodeling of embryonic tissues, with the power to turn an epithelial somite into sclerotome mesenchyme, and the neural crest into mesenchyme that migrates to many targets. Thus, the time has come for serious study of the underlying mechanisms and the signaling pathways that are used to form the mesenchymal cell in the embryo. In this review, I discuss EMT centers in the embryo that are ready for such serious study and review our current understanding of the mechanisms used for EMT in vitro, as well as those that have been implicated in EMT in vivo. The purpose of this review is not to describe every study published in this rapidly expanding field but rather to stimulate the interest of the reader in the study of the role of the mesenchymal cell in the embryo, where it plays profound roles in development. In the adult, mesenchymal cells may give rise to metastatic tumor cells and other pathological conditions that we will touch on at the end of the review. 相似文献