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81.
RNA interference (RNAi) is a cellular process regulating gene expression and participating in innate defense in many organisms. RNAi has also been utilized as a tool to query gene function and is being developed as a therapeutic strategy for several diseases. Synthetic small interfering (siRNAs) or expressed stem–loop RNAs (short-hairpin RNAs [shRNAs] or artificial microRNAs [miRNAs]) have been delivered to cultured cells and organisms to inhibit expression of a variety of genes. A persistent question in the field, however, is which RNAi expression system is most suitable for distinct applications. To date, shRNA- and artificial miRNA-based strategies have been compared with conflicting results. In prior comparisons, sequences required for efficient RNAi processing and loading of the intended antisense strand into the RNAi-induced silencing complex (RISC) were not considered. We therefore revisited the shRNA–miRNA comparison question. Initially, we developed an improved artificial miRNA vector and confirmed the optimal shRNA configuration by altering structural features of these RNAi substrates. Subsequently, we engineered and compared shRNA- and miRNA-based RNAi expression vectors that would be processed to yield similar siRNAs that exhibit comparable strand biasing. Our results demonstrate that when comparison variables are minimized, the shRNAs tested were more potent than the artificial miRNAs in mediating gene silencing independent of target sequence and experimental setting (in vitro and in vivo). In addition, we show that shRNAs are expressed at considerably higher levels relative to artificial miRNAs, thus providing mechanistic insight to explain their increased potency. 相似文献
82.
Vidushi S Patel Steven JB Cooper Janine E Deakin Bob Fulton Tina Graves Wesley C Warren Richard K Wilson Jennifer AM Graves 《BMC biology》2008,6(1):34
Background
Vertebrate alpha (α)- and beta (β)-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the α- and β-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil β-globin gene (ω) in the marsupial α-cluster, however, suggested that duplication of the α-β cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous α- and β-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus), to explore haemoglobin evolution at the stem of the mammalian radiation. 相似文献83.
84.
Martinus AM van Boekel Erik R Vossenaar Frank HJ van den Hoogen Walther J van Venrooij 《Arthritis research & therapy》2001,4(2):87
The diagnosis of rheumatoid arthritis (RA) is primarily based on clinical symptoms, so it is often difficult to diagnose RA in very early stages of the disease. A disease-specific autoantibody that could be used as a serological marker would therefore be very useful. Most autoimmune diseases are characterized by a polyclonal B-cell response targeting multiple autoantigens. These immune responses are often not specific for a single disease. In this review, the most important autoantibody/autoantigen systems associated with RA are described and their utility as a diagnostic and prognostic tool, including their specificity, sensitivity and practical application, is discussed. We conclude that, at present, the antibody response directed to citrullinated antigens has the most valuable diagnostic and prognostic potential for RA. 相似文献
85.
Annette AM Gerritsen Rob JPM Scholten Willem JJ Assendelft Herman Kuiper Henrica CW de Vet Lex M Bouter 《BMC neurology》2001,1(1):8-7
Background
Carpal tunnel syndrome is a common disorder, which can be treated with surgery or conservative options. However, there is insufficient evidence and no consensus among physicians with regard to the preferred treatment for carpal tunnel syndrome. Therefore, a randomized controlled trial is conducted to compare the short- and long-term efficacy of surgery and splinting in patients with carpal tunnel syndrome. An attempt is also made to avoid the (methodological) limitations encountered in earlier trials on the efficacy of various treatment options for carpal tunnel syndrome. 相似文献86.
Forbes SH; Hogg JT; Buchanan FC; Crawford AM; Allendorf FW 《Molecular biology and evolution》1995,12(6):1106-1113
We compared genotypes at eight (AC)n microsatellite loci in domestic sheep
(Ovis aries) and wild Rocky Mountain bighorn sheep (O. canadensis). The
domestic sheep had greater genetic variation, higher allele-size variances,
and larger allele sizes than the wild sheep. Accumulating evidence from
higher taxonomic comparisons shows that these parameters are biased if
microsatellite loci are selected in one taxon and used in another. Our
results demonstrate similar biases between congeneric species. We compared
standard measures of genetic variation, differentiation, and distance
within and between species (H, D, FST) to newer measures based on
allele-size variance (SW, SB, RST). The size-based distances better
detected species-level divergence, but standard measures better
distinguished allopatric populations. Empirical calibration of these
measures at the subspecies level is needed to establish their useful
ranges.
相似文献
87.
A plasmid library of Acinetobacter calcoaceticus HindIII fragments was
constructed, and clones that complemented an Escherichia coli pabA mutant
were selected. Plasmids containing a 3.9-kb fragment of A. calcoaceticus
DNA that also complemented E. coli trpD and trpC-(trpF+) mutants were
obtained. We infer that complementation of E. coli pabA mutants was the
result of the expression of the amphibolic anthranilate-
synthase/p-aminobenzoate-synthase glutamine-amidotransferase gene and that
the plasmid insert carried the entire trpGDC gene cluster. In E. coli
minicells, the plasmid insert directed the synthesis of polypeptides of
44,000, 33,000, and 20,000 daltons, molecular masses that are consistent
with the reported molecular masses of phosphoribosylanthranilate
transferase, indoleglycerol-phosphate synthase, and anthranilate-synthase
component II, respectively. A 3,105- bp nucleotide sequence was determined.
Comparison of the A. calcoaceticus trpGDC sequences with other known trp
gene sequences has allowed insight into (1) the evolution of the amphibolic
trpG gene, (2) varied strategies for coordinate expression of trp genes,
and (3) mechanisms of gene fusions in the trp operon.
相似文献
88.
Bellis M; Jubier-Maurin V; Dod B; Vanlerberghe F; Laurent AM; Senglat C; Bonhomme F; Roizes G 《Molecular biology and evolution》1987,4(4):351-363
The presence of the L1 sequences, L1Md4 next to the pseudogene beta h3 and
I12 found in the twelfth intron of the albumin gene, in certain strains of
laboratory mice but not of others has led to the suggestion that these
sequences were recent insertions into the Mus mus domesticus genome. To be
sure that they are really recent insertions and not relics of an ancestral
chromosome, we investigated the presence or absence of these sequences in
populations of wild mice belonging to the semispecies M. m. domesticus and
M. m. musculus as well as in other species of the genus Mus and in related
murids. The sequence I12 in the albumin gene was found in 34% of the
chromosomes of the wild mice belonging to M. m. domesticus and to a lesser
extent (6%) in M. m. musculus. Of 114 M. m. domesticus chromosomes, L1Md4
was found in only nine, seven of which came from the same locality. Its
presence was associated with the haplotype Hbbp, which is relatively rare
in European populations of M. musculus. Since there was no evidence for the
presence of these two L1 sequences in more distantly related species, we
conclude that they are recent insertions in the M. musculus genome.
相似文献
89.
B Chevassus JM Blanc P Bergot L Casenave AM Escaffre F Hérioux N Kaushik R Lanneberre 《遗传、选种与进化》1979,11(1):79-92
90.
Bassi AM Romano P Mangini S Colombo M Canepa C Nanni G Casu A 《Journal of biomedical science》2005,12(3):457-466
Summary We analysed the action, in rats in vivo, of the protein isoprenylation inhibitor perillyl alcohol (POH) and that of vitamin A, alone or in association, on m-RNA and protein expression of farnesyltransferases (FTases α and β subunits) and their protein substrates RhoA and RhoB, in isolated hepatocytes. Combined administration of POH and vitamin A induced a sharp decrease in FTase α protein after 96 h, suggesting an involvement not only of farnesyltransferases but also of geranylgeranyltransferases, which share the FTase α protein. FTase β protein did not decrease. POH plus vitamin A, in contrast with POH or vitamin A alone, induced a decrease in RhoB protein, probably because of different cleavages. No modification was observed in RhoA protein. Vitamin A alone increased RhoB m-RNA and protein expression. As one of the functions of RhoB is cell polarisation, these data support our previous hypothesis of a polarised transport of vitamin A from hepatocytes to hepatic stellate cells. As the behaviours of m-RNAs and proteins in this study were often different, cytoplasmic metabolic pathways must be considered for the parameters studied. The behaviour of Rho B, which is thought to have an antioncogene function, is discussed in view of its isoprenylated forms in the membranes. These preliminary findings stress the need, when studying the association of two isoprenoids in cancer therapy, to consider normal as well as tumour-bearing animals. 相似文献