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排序方式: 共有125条查询结果,搜索用时 15 毫秒
101.
Sze SH; Roytberg MA; Gelfand MS; Mironov AA; Astakhova TV; Pevzner PA 《Bioinformatics (Oxford, England)》1998,14(1):14-19
MOTIVATION: Gene annotation is the final goal of gene prediction
algorithms. However, these algorithms frequently make mistakes and
therefore the use of gene predictions for sequence annotation is hardly
possible. As a result, biologists are forced to conduct time-consuming gene
identification experiments by designing appropriate PCR primers to test
cDNA libraries or applying RT-PCR, exon trapping/amplification, or other
techniques. This process frequently amounts to 'guessing' PCR primers on
top of unreliable gene predictions and frequently leads to wasting of
experimental efforts. RESULTS: The present paper proposes a simple and
reliable algorithm for experimental gene identification which bypasses the
unreliable gene prediction step. Studies of the performance of the
algorithm on a sample of human genes indicate that an experimental protocol
based on the algorithm's predictions achieves an accurate gene
identification with relatively few PCR primers. Predictions of PCR primers
may be used for exon amplification in preliminary mutation analysis during
an attempt to identify a gene responsible for a disease. We propose a
simple approach to find a short region from a genomic sequence that with
high probability overlaps with some exon of the gene. The algorithm is
enhanced to find one or more segments that are probably contained in the
translated region of the gene and can be used as PCR primers to select
appropriate clones in cDNA libraries by selective amplification. The
algorithm is further extended to locate a set of PCR primers that uniformly
cover all translated regions and can be used for RT-PCR and further
sequencing of (unknown) mRNA.
相似文献
102.
Damon J. A. Toth Adi V. Gundlapalli Wiley A. Schell Kenneth Bulmahn Thomas E. Walton Christopher W. Woods Catherine Coghill Frank Gallegos Matthew H. Samore Frederick R. Adler 《PLoS pathogens》2013,9(8)
Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data from exposures and infections of humans and non-human primates are often contradictory. We review existing quantitative inhalational anthrax dose-response models in light of criteria we propose for a model to be useful and defensible. To satisfy these criteria, we extend an existing mechanistic competing-risks model to create a novel Exposure–Infection–Symptomatic illness–Death (EISD) model and use experimental non-human primate data and human epidemiological data to optimize parameter values. The best fit to these data leads to estimates of a dose leading to infection in 50% of susceptible humans (ID50) of 11,000 spores (95% confidence interval 7,200–17,000), ID10 of 1,700 (1,100–2,600), and ID1 of 160 (100–250). These estimates suggest that use of a threshold to human infection of 600 spores (as suggested in the literature) underestimates the infectivity of low doses, while an existing estimate of a 1% infection rate for a single spore overestimates low dose infectivity. We estimate the median time from exposure to onset of symptoms (incubation period) among untreated cases to be 9.9 days (7.7–13.1) for exposure to ID50, 11.8 days (9.5–15.0) for ID10, and 12.1 days (9.9–15.3) for ID1. Our model is the first to provide incubation period estimates that are independently consistent with data from the largest known human outbreak. This model refines previous estimates of the distribution of early onset cases after a release and provides support for the recommended 60-day course of prophylactic antibiotic treatment for individuals exposed to low doses. 相似文献
103.
Host PrP glycosylation: a major factor determining the outcome of prion infection 总被引:1,自引:0,他引:1 下载免费PDF全文
Tuzi NL Cancellotti E Baybutt H Blackford L Bradford B Plinston C Coghill A Hart P Piccardo P Barron RM Manson JC 《PLoS biology》2008,6(4):e100
The expression of the prion protein (PrP) is essential for transmissible spongiform encephalopathy (TSE) or prion diseases to occur, but the underlying mechanism of infection remains unresolved. To address the hypothesis that glycosylation of host PrP is a major factor influencing TSE infection, we have inoculated gene-targeted transgenic mice that have restricted N-linked glycosylation of PrP with three TSE strains. We have uniquely demonstrated that mice expressing only unglycosylated PrP can sustain a TSE infection, despite altered cellular location of the host PrP. Moreover we have shown that brain material from mice infected with TSE that have only unglycosylated PrPSc is capable of transmitting infection to wild-type mice, demonstrating that glycosylation of PrP is not essential for establishing infection within a host or for transmitting TSE infectivity to a new host. We have further dissected the requirement of each glycosylation site and have shown that different TSE strains have dramatically different requirements for each of the glycosylation sites of host PrP, and moreover, we have shown that the host PrP has a major role in determining the glycosylation state of de novo generated PrPSc. 相似文献
104.
L. J. Farrow S. G. Lamb N. F. Coghill R. L. Lindon Jill Preece A. J. Zuckerman J. S. Stewart 《BMJ (Clinical research ed.)》1974,3(5923):83-86
During the first 12 months of a total population survey 249 patients were seen with viral hepatitis. A total of 215 of these were tested for hepatitis B antigen (HB Ag) by radioimmunoassay and 32 (15%) were positive.More than five times as many men (27) as women (5) were HBAg positive and 19 of the men were between the ages of 20 and 39 years. There were only four drug addicts among those tested, two of whom were positive, as were two of the four patients who were tattooed.Sixty out of 86 children (under 15 years) were tested for HBAg and none was positive. 相似文献
105.
D. James G. Asherson I. Chanarin N. Coghill S. Hamilton R. L. Himsworth D. Webster 《BMJ (Clinical research ed.)》1974,4(5943):494
Evidence of cell-mediated immunity to gastric intrinsic factor was present in 86% of patients with pernicious anaemia and in at least 13% of patients with hyperthyroidism, 21% of patients with atrophic gastritis, and four out of nine (46%) patients with hypogammaglobulinaemia. Controls gave negative results. The four patients with hypogammaglobulinaemia and cell-mediated immunity to intrinsic factor had evidence of impaired gastric function. 相似文献
106.
Synopsis The electron microscopic histochemistry of mucosubstances in sigmoidoscopically and microscopically normal rectal biopsies was studied using techniques currently available. The deposition of Alcian Blue and Ruthenium Red and the distribution of Concanavalin A receptors were limited to the epithelial cell borders. Mucosubstances in the fuzzy coat, Golgi apparatus, lysosomes and secretory vesicles were demonstrated by the periodic acid—chromic acid oxidation methods. Glycogen was demonstrated in the epithelium by periodate oxidation methods and the complex cyanide technique. There was little difference in the distribution of mucosubstances in the epithelial cells at any level of the crypts. Phosphotungstic acid staining under controlled conditions gave a similar distribution of mucosubstances to those revealed by the oxidation techniques. 相似文献
107.
108.
Zimmerman PA; Katholi CR; Wooten MC; Lang-Unnasch N; Unnasch TR 《Molecular biology and evolution》1994,11(3):384-392
Polymerase chain reaction (PCR) products were characterized for a repeated
sequence family (designated "O-150") of the human filarial parasite
Onchocerca volvulus. In phylogenetic inferences, the O-150 sequences
clustered into closely related groups, suggesting that concerted evolution
maintains sequence homology in this family. Using a novel mathematical
model based on a nested application of an analysis of variance, we
demonstrated that African rainforest and savannah strain parasite
populations are significantly different. In contrast, parasites collected
in the New World are indistinguishable from African savannah strains of O.
volvulus. This finding supports the hypothesis that onchocerciasis was
recently introduced into the New World, possibly as a result of the slave
trade.
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109.
McGrath MJ Cottle DL Nguyen MA Dyson JM Coghill ID Robinson PA Holdsworth M Cowling BS Hardeman EC Mitchell CA Brown S 《The Journal of biological chemistry》2006,281(11):7666-7683
Four and a half LIM protein 1 (FHL1/SLIM1) is highly expressed in skeletal and cardiac muscle; however, the function of FHL1 remains unknown. Yeast two-hybrid screening identified slow type skeletal myosin-binding protein C as an FHL1 binding partner. Myosin-binding protein C is the major myosin-associated protein in striated muscle that enhances the lateral association and stabilization of myosin thick filaments and regulates actomyosin interactions. The interaction between FHL1 and myosin-binding protein C was confirmed using co-immunoprecipitation of recombinant and endogenous proteins. Recombinant FHL2 and FHL3 also bound myosin-binding protein C. FHL1 impaired co-sedimentation of myosin-binding protein C with reconstituted myosin filaments, suggesting FHL1 may compete with myosin for binding to myosin-binding protein C. In intact skeletal muscle and isolated myofibrils, FHL1 localized to the I-band, M-line, and sarcolemma, co-localizing with myosin-binding protein C at the sarcolemma in intact skeletal muscle. Furthermore, in isolated myofibrils FHL1 staining at the M-line appeared to extend partially into the C-zone of the A-band, where it co-localized with myosin-binding protein C. Overexpression of FHL1 in differentiating C2C12 cells induced "sac-like" myotube formation (myosac), associated with impaired Z-line and myosin thick filament assembly. This phenotype was rescued by co-expression of myosin-binding protein C. FHL1 knockdown using RNAi resulted in impaired myosin thick filament formation associated with reduced incorporation of myosin-binding protein C into the sarcomere. This study identified FHL1 as a novel regulator of myosin-binding protein C activity and indicates a role for FHL1 in sarcomere assembly. 相似文献
110.
Synergistic anion and metal binding to the ferric ion-binding protein from Neisseria gonorrhoeae 总被引:3,自引:0,他引:3
Guo M Harvey I Yang W Coghill L Campopiano DJ Parkinson JA MacGillivray RT Harris WR Sadler PJ 《The Journal of biological chemistry》2003,278(4):2490-2502
The 34-kDa periplasmic iron-transport protein (FBP) from Neisseria gonorrhoeae (nFBP) contains Fe(III) and (hydrogen)phosphate (synergistic anion). It has a characteristic ligand-to-metal charge-transfer absorption band at 481 nm. Phosphate can be displaced by (bi)carbonate to give Fe.CO(3).nFBP (lambda(max) 459 nm). The local structures of native Fe-PO(4)-nFBP and Fe.CO(3).nFBP were determined by EXAFS at the FeK edge using full multiple scattering analysis. The EXAFS analysis reveals that both phosphate and carbonate ligands bind to FBP in monodentate mode in contrast to transferrins, which bind carbonate in bidentate mode. The EXAFS analysis also suggests an alternative to the crystallographically determined position of the Glu ligand, and this in turn suggests that an H-bonding network may help to stabilize monodentate binding of the synergistic anion. The anions oxalate, pyrophosphate, and nitrilotriacetate also appear to serve as synergistic anions but not sulfate or perchlorate. The oxidation of Fe(II) in the presence of nFBP led to a weak Fe(III).nFBP complex (lambda(max) 471 nm). Iron and phosphate can be removed from FBP at low pH (pH 4.5) in the presence of a large excess of citrate. Apo-FBP is less soluble and less stable than Fe.nFBP and binds relatively weakly to Ga(III) and Bi(III) but not to Co(III) ions, all of which bind strongly to apo-human serum transferrin. 相似文献