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101.
Shui-Lian Yu Paul KS Chan Chun-Kwok Wong Cheuk-Chun Szeto Suzanne C Ho Karine So May MY Yu So-Fan Yim Tak-Hong Cheung Martin CS Wong Jo LK Cheung Apple CM Yeung Edmund K Li Lai-Shan Tam 《Arthritis research & therapy》2012,14(2):R80
IntroductionPrevalence of an abnormal Papanicolaou smear was significantly increased in lupus patients in cross-sectional studies, associated with a higher prevalence of high-risk human papillomavirus (HPV) infection. The nucleic acid-specific Toll-like receptors (TLRs) locate at the endolysosomal compartments and trigger the induction of cytokines for the innate immune response. This study evaluated whether abnormal host innate immune response in lupus patients may enhance HPV persistence.MethodsProtein levels of TLRs 3, 7, 8 and 9 in cervical epithelial cells of lupus patients and controls with or without HPV infection were assessed using flow cytometry. Characteristics associated with the differential expression of TLRs in systemic lupus erythematosus (SLE) were elucidated. The effect and interferon-stimulated genes (ISGs) (ISG15 and Mx-1) gene expressions were then measured in oncogenic HeLa (HPV18), CaSki (HPV) and C33A (HPV negative) cell lines using flow cytometry and quantitative real-time PCR. Ex vivo productions of cytokines and interferon-gamma (IFN-γ) upon TLR ligands stimulations were subsequently measured using cytometric bead array and ELISA.ResultsFor subjects with HPV infection, levels of TLR3 and TLR7 were significantly lower in lupus patients compared with controls. Significantly decreased TLRs 7, 8 and 9 levels were observed in HPV-negative SLE compared to healthy controls. For SLE with and without HPV infection, TLR7 and 9 levels were significantly lower in infected SLE than those in HPV-negative patients. Independent explanatory variables associated with down-regulation of TLR7 level included HPV infection and a higher cumulative dose of prednisolone; while a higher cumulative dose of hydroxychloroquine and HPV infection were associated with down-regulation of TLR9 level. In cervical cell lines, TLRs 3, 7, 8, 9 protein levels and antiviral ISG15 and Mx-1 gene expressions were inhibited in two oncogenic HPV types. Functional data showed that the induction of pro-inflammatory cytokines by TLR ligands (R837, ssRNA and ODN2395) was greatly impaired in CaSki and HeLa than C33A cells.ConclusionsIn conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection. Upon infection, HPV further down-regulate TLR7 and 9 levels for viral persistence. Furthermore, reduction of nucleic acid-sensing TLRs 7, 8 and 9 in carcinogenic HPVs ensures that the expression of inducible pro-inflammatory cytokines is minimized to prevent the expression of antiviral ISGs (ISG15 and Mx-1) on a biologically relevant antiviral response. 相似文献
102.
Jonathan CM Clark Toru Akiyama Crispin R Dass Peter FM Choong 《Cancer cell international》2010,10(1):20
Background
Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. 相似文献103.
A mathematical approach was developed to model and optimize selection on multiple known quantitative trait loci (QTL) and polygenic estimated breeding values in order to maximize a weighted sum of responses to selection over multiple generations. The model allows for linkage between QTL with multiple alleles and arbitrary genetic effects, including dominance, epistasis, and gametic imprinting. Gametic phase disequilibrium between the QTL and between the QTL and polygenes is modeled but polygenic variance is assumed constant. Breeding programs with discrete generations, differential selection of males and females and random mating of selected parents are modeled. Polygenic EBV obtained from best linear unbiased prediction models can be accommodated. The problem was formulated as a multiple-stage optimal control problem and an iterative approach was developed for its solution. The method can be used to develop and evaluate optimal strategies for selection on multiple QTL for a wide range of situations and genetic models. 相似文献
104.
Eric A Gaucher Logan G Graddy Tang Li Rosalia CM Simmen Frank A Simmen David R Schreiber David A Liberles Christine M Janis Steven A Benner 《BMC biology》2004,2(1):19
Background
Joining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system. 相似文献105.
King SM Donangelo CM Knutson MD Walter PB Ames BN Viteri FE King JC 《Experimental biology and medicine (Maywood, N.J.)》2008,233(6):701-707
The aim of this study was to determine whether women with low iron stores (plasma ferritin 相似文献
106.
Relapsing polychondritis (RP) is an autoimmune disease that affects extra-articular cartilage. Matrilin-1-induced relapsing
polychondritis (MIRP) is a model for RP and is useful for studies of the pathogenic mechanisms in this disease. There are
indications that the major histocompatibility complex (MHC) class II plays a major role in RP, since DR4+ patients are more commonly affected than controls. We have now addressed the role of the MHC region, as well as the non-MHC
contribution, using congenic mouse strains. Of the MHC congenic strains, B10.Q (H2
q
) was the most susceptible, the B10.P (H2
p
) and B10.R (H2
r
) strains developed mild disease, while B10 strains carrying the v, b, f, or u H2 haplotypes were resistant. A slight variation
of susceptibility of H2
q
strains (B10.Q> C3H.Q> DBA/1) was observed and the (B10.Q × DBA/1)F1 was the most susceptible of all strains. Furthermore, macrophages and CD4+ T cells were the most prominent cell types in inflammatory infiltrates of the tracheal cartilage. Macrophages are the major
source of many cytokines, such as interleukin-10 (IL-10), which is currently being tested as a therapeutic agent in several
autoimmune diseases. We therefore investigated B10.Q mice devoid of IL-10 through gene deletion and found that they developed
a significantly more severe disease, with an earlier onset, than their heterozygous littermates. In conclusion, MHC genes,
as well as non-MHC genes, are important for MIRP induction, and IL-10 plays a major suppressive role in cartilage inflammation
of the respiratory tract. 相似文献
107.
Members of the ZFY and ZNF6 gene families have been cloned from species
representing different taxa and different modes of sex determination.
Comparisons of these genes show the ZFY-like and ZNF6 sequences to be
strongly conserved across marsupials, birds, and lepidosaurians. Sequence
analyzed by neighbor-joining indicated that both gene families are
monophyletic with a high bootstrap value. Pairing of sequences from males
and females of nonmammalian species showed there to be no significant
difference between male and female sequences from a single species,
consistent with autosomal locations. The molecular distances between murine
Zfy-1, Zfy-2, and other ZFY-like sequences suggested that Zfy genes have
undergone a period of rapid evolutionary change not seen in human ZFY.
相似文献
108.
Transposable elements induce spontaneous mutations, promote genome
rearrangements, regulate gene expression, and participate in the horizontal
spread of genes encoding traits such as antibiotic resistance among
bacterial genera too distantly related to undergo homologous recombination.
Here we review the bacterial transposon Tn5 and focus on those aspects of
its functional organization and transposition which provide insights into
how it and other elements may have arisen, proliferated, and evolved.
相似文献
109.
The phylogenetic position of Rhopalura ophiocomae (Orthonectida) based on 18S ribosomal DNA sequence analysis 总被引:2,自引:0,他引:2
Hanelt B; Van Schyndel D; Adema CM; Lewis LA; Loker ES 《Molecular biology and evolution》1996,13(9):1187-1191
The Orthonectida is a small, poorly known phylum of parasites of marine
invertebrates. Their phylogenetic placement is obscure; they have been
considered to be multicellular protozoans, primitive animals at a
"mesozoan" grade of organization, or secondarily simplified flatworm- like
organisms. The best known species in the phylum, Rhopalura ophiocomae, was
collected on San Juan Island, Wash. and a complete 18S rDNA sequence was
obtained. Using the models of minimum evolution and parsimony, phylogenetic
analyses were undertaken and the results lend support to the following
hypotheses about orthonectids: (1) orthonectids are more closely aligned
with triploblastic metazoan taxa than with the protist or diploblastic
metazoan taxa considered in this analysis; (2) orthonectids are not derived
members of the phylum Platyhelminthes; and (3) orthonectids and rhombozoans
are not each other's closest relatives, thus casting further doubt on the
validity of the phylum Mesozoa previously used to encompass both groups.
相似文献
110.
Distribution of the molossinus allele of Sry, the testis-determining gene, in wild mice 总被引:3,自引:0,他引:3
Nagamine CM; Shiroishi T; Miyashita N; Tsuchiya K; Ikeda H; Takao N; Wu XL; Jin ML; Wang FS; Kryukov AP 《Molecular biology and evolution》1994,11(6):864-874
When the Y chromosome of the laboratory inbred mouse strain C57BL/6 (B6) is
replaced by the Y of certain strains of Mus musculus domesticus, testis
determination fails and all XY fetuses develop either as hermaphrodites or
XY females (XY sex reversal). This suggests the presence of at least two
alleles of Sry, the male-determining gene on the Y:M. m. domesticus and B6.
The B6 Y chromosome is derived from the Japanese house mouse, M. m.
molossinus and therefore carries a molossinus Sry allele. As a first step
to determine how the molossinus Sry allele evolved, its distribution
pattern was determined in wild mice. The cumulative data of 96 M. musculus
samples obtained from 58 geographical locations in Europe, North Africa,
and Asia show the molossinus Sry allele is restricted to Japan and the
neighboring Asian mainland and confirm that Japanese M. m. molossinus mice
were derived in part from a race of M. m. musculus from Korea or Manchuria.
Sry polymorphisms, as illustrated by the molossinus Sry allele, can serve
as molecular markers for studies on the evolution of wild M. musculus
populations and can help determine the role sex determination plays in
speciation.
相似文献