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31.
Amrita Pati Cecilia Vasquez-Robinet Lenwood S Heath Ruth Grene TM Murali 《BMC bioinformatics》2006,7(1):218-14
Background
Modeling of cis-elements or regulatory motifs in promoter (upstream) regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions. 相似文献32.
Miguel?Lacerda Penny?L?Moore Nobubelo?K?Ngandu Michael?Seaman Elin?S?Gray Ben?Murrell Mohan?Krishnamoorthy Molati?Nonyane Maphuti?Madiga Constantinos?Kurt?Wibmer Daniel?Sheward Robert?T?Bailer Hongmei?Gao Kelli?M?Greene Salim?S?Abdool?Karim John?R?Mascola Bette?TM?Korber David?C?Montefiori Lynn?Morris Carolyn?Williamson Cathal?SeoigheEmail author the CAVD-NSDP Consortium 《Virology journal》2013,10(1):347
Background
Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine.Methods
We have developed a computational approach that can identify key amino acids within the HIV-1 envelope glycoprotein that influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence alignment and neutralization titers for a panel of viruses, the method works by fitting a phylogenetic model that allows the amino acid frequencies at each site to depend on neutralization sensitivities. Sites at which viral evolution influences neutralization sensitivity were identified using Bayes factors (BFs) to compare the fit of this model to that of a null model in which sequences evolved independently of antibody sensitivity. Conformational epitopes were identified with a Metropolis algorithm that searched for a cluster of sites with large Bayes factors on the tertiary structure of the viral envelope.Results
We applied our method to ID50 neutralization data generated from seven HIV-1 subtype C serum samples with neutralization breadth that had been tested against a multi-clade panel of 225 pseudoviruses for which envelope sequences were also available. For each sample, between two and four sites were identified that were strongly associated with neutralization sensitivity (2ln(BF)?>?6), a subset of which were experimentally confirmed using site-directed mutagenesis.Conclusions
Our results provide strong support for the use of evolutionary models applied to cross-sectional viral neutralization data to identify the epitopes of serum antibodies that confer neutralization breadth.33.
Entomopathogenic nematodes (EPN) are efficient biological pest control agents. Population genetics studies on EPN are seldom
known. Therefore, it is of interest to evaluate the significance of molecular sampling method (MSM) for accuracy, time needed, and
cost effectiveness over traditional sampling method (TSM). The study was conducted at the Mohican Hills golf course at the state
of Ohio where the EPN H. bacteriophora has been monitored for 18 years. The nematode population occupies an area of
approximately 3700 m2 with density range from 0.25-2 per gram soil. Genetic diversity of EPN was studied by molecular sampling
method (MSM) and traditional sampling method (TSM) using the mitochondrial gene pcox1. The MSM picked 88% in compared to
TSM with only 30% of sequenced cox 1 gene. All studied genetic polymorphism measures (sequence and haplotype) showed high
levels of genetic diversity of MSM over TSM. MSM minimizes the chance of mitochondrial genes amplification from non target
organisms (insect or other contaminating microorganisms). Moreover, it allows the sampling of more individuals with a reliable
and credible representative sample size. Thus, we show that MSM supersedes TSM in labour intensity, time consumption and
requirement of no special experience and efficiency. 相似文献
34.
Yvonne P de Visser Frans J Walther El Houari Laghmani Hester Boersma Arnoud van der Laarse Gerry TM Wagenaar 《Respiratory research》2009,10(1):1-16
Background
Phosphodiesterase-5 inhibition with sildenafil has been used to treat severe pulmonary hypertension and bronchopulmonary dysplasia (BPD), a chronic lung disease in very preterm infants who were mechanically ventilated for respiratory distress syndrome.Methods
Sildenafil treatment was investigated in 2 models of experimental BPD: a lethal neonatal model, in which rat pups were continuously exposed to hyperoxia and treated daily with sildenafil (50–150 mg/kg body weight/day; injected subcutaneously) and a neonatal lung injury-recovery model in which rat pups were exposed to hyperoxia for 9 days, followed by 9 days of recovery in room air and started sildenafil treatment on day 6 of hyperoxia exposure. Parameters investigated include survival, histopathology, fibrin deposition, alveolar vascular leakage, right ventricular hypertrophy, and differential mRNA expression in lung and heart tissue.Results
Prophylactic treatment with an optimal dose of sildenafil (2 × 50 mg/kg/day) significantly increased lung cGMP levels, prolonged median survival, reduced fibrin deposition, total protein content in bronchoalveolar lavage fluid, inflammation and septum thickness. Treatment with sildenafil partially corrected the differential mRNA expression of amphiregulin, plasminogen activator inhibitor-1, fibroblast growth factor receptor-4 and vascular endothelial growth factor receptor-2 in the lung and of brain and c-type natriuretic peptides and the natriuretic peptide receptors NPR-A, -B, and -C in the right ventricle. In the lethal and injury-recovery model we demonstrated improved alveolarization and angiogenesis by attenuating mean linear intercept and arteriolar wall thickness and increasing pulmonary blood vessel density, and right ventricular hypertrophy (RVH).Conclusion
Sildenafil treatment, started simultaneously with exposure to hyperoxia after birth, prolongs survival, increases pulmonary cGMP levels, reduces the pulmonary inflammatory response, fibrin deposition and RVH, and stimulates alveolarization. Initiation of sildenafil treatment after hyperoxic lung injury and continued during room air recovery improves alveolarization and restores pulmonary angiogenesis and RVH in experimental BPD. 相似文献35.
Sari Haikola Wilhelm Fortelius Robert B. O''Hara Mikko Kuussaari Niklas Wahlberg Ilik J. Saccheri Michael C. Singer Ilkka Hanski 《Conservation Genetics》2001,2(4):325-335
The effects of inbreeding on fitness and themaintenance of genetic load in metapopulationsof the endangered Glanville fritillarybutterfly (Melitaea cinxia) were examinedin four laboratory experiments. In FinlandM. cinxia occurs as a large metapopulationconsisting of small local populations with fastturnover, whereas in southern France thespecies has a more continuous populationstructure. In the experiments, we compared theperformance of crosses between full sibs,crosses between members of different familieswithin populations, and crosses betweenindividuals from different populations. Theseexperiments were replicated using insects fromtwo different regions, Finland and southernFrance, between which the frequency of naturalinbreeding should differ substantially becauseof differing population structure. In Finnishbutterflies, the rate of successful mating waslower among insects derived from small thanfrom large natural populations, probablyreflecting the effect of past inbreedinghistory. Mating between full sibs lowered egghatching rate in all experiments. Thisreduction of egg hatching rate was more severeamong French butterflies with a more continuouspopulation structure than among Finnishbutterflies with small naturally fragmentedpopulations and with a history of repeatedrounds of inbreeding in the past. This resultsuggests that recurrent inbreeding has led topartial purging of deleterious recessives fromthe Finnish metapopulation. Nonetheless,substantial genetic load still remains in thismetapopulation, and we discuss possible reasonswhy this should be the case. 相似文献
36.
Levels of fos, ets2, and myb proto-oncogene RNAs correlate with segregation of chromosome 11 of normal cells and with suppression of tumorigenicity in human cell hybrids. 总被引:1,自引:0,他引:1
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B M O''Hara H P Klinger T Curran Y D Zhang D G Blair 《Molecular and cellular biology》1987,7(8):2941-2946
The tumorigenicity in nude mice of human carcinoma-derived D98AH2 (D98) cells is suppressed when cell hybrids are made by fusing these cells with normal human diploid cells. Selection for hybrids that have segregated chromosomes results in the recovery of tumorigenic segregants. These segregants have all lost at least one copy of chromosome 11 of the diploid cell parent. Earlier we found that the parental D98 cells had detectable levels of mRNA specific for 13 of 21 proto-oncogenes examined. To determine if transregulation of proto-oncogenes by genes of the normal cell occurs in such hybrids, the steady-state levels of mRNA specific to 22 proto-oncogenes in the parental cells were compared with those of nontumorigenic D98 X human diploid hybrids as well as with those of their tumorigenic segregants and with the cells of the resulting tumors. The only chromosome consistently segregated in the latter was chromosome 11 of the diploid cell. fos and ets2 RNA levels and the amount of fos protein were consistently elevated in the segregants compared with amounts in the original hybrids. An unexpected finding was the inverse relationship for myb RNA that was barely detected in the parental D98 cells but was at least 10-fold elevated in hybrids that did not have segregated chromosomes compared with those that did. These patterns were evident in RNAs prepared from both subconfluent and confluent cell cultures. The findings suggest that genes of the normal cell parent can affect proto-oncogene expression. Whether the genes affecting fos, ets2, and myb RNA levels are on chromosome 11 and whether these alterations are causally related to the tumorigenic phenotype of the hybrid remain to be determined. 相似文献
37.
Denise M. O''Hara Charles R. Harrington Peter E. Reynolds 《FEMS microbiology letters》1989,57(1):97-104
The additional penicillin-binding protein (PBP 2') that is important in determining intrinsic resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA) has been detected immunologically in strains from a variety of world-wide locations. This additional protein has also been definitively identified both immunologically and as a PBP in methicillin-resistant strains of S. epidermidis (MRSE). The assay described is rapid, specific and sensitive and has been used to detect PBP 2' in S. haemolyticus but not in beta-lactam resistant Streptococci. 相似文献
38.
39.
Isolated populations of drosophila pseudoobscura, separated from North
American populations by about 2,400 km, were found in Colombia in 1960. We
compared for sequences of the small ribosomal RNA (srRNA) gene on the
mitochondria between North American and Colombian D. pseudoobscura in order
to clarify the age of the Colombian isolates. The North American
populations were not genetically different from each other but were
genetically different from the Colombian populations. The Mexican strains
represent the area from which the Colombian founders might have come. The
estimated net nucleotide divergence between Mexican and Colombian D.
pseudoobscura indicates that the Colombian population is not an ancient
lineage. Phylogenies using both distance and parsimony methodologies
reinforced this conclusion. The Colombian samples group together with both
methods but, according to the bootstrap analysis, not significantly. It
appears that the populations have not been separated long enough for their
DNA sequences to show much divergence.
相似文献
40.
Length Heteroplasmy of Sturgeon Mitochondrial DNA: An Illegitimate Elongation Model 总被引:38,自引:8,他引:30
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N. E. Buroker J. R. Brown T. A. Gilbert P. J. O''Hara A. T. Beckenbach W. K. Thomas M. J. Smith 《Genetics》1990,124(1):157-163
Extensive length polymorphism and heteroplasmy (multiple forms within an individual) of the D-loop region are observed in mitochondrial DNA of the white sturgeon (Acipenser transmontanus). The nucleotide sequence of this region, for both a short and a long form, shows that the differences are due to variable numbers of a perfect 82-bp direct repeat. We propose a model for the replicative origin of length differences, involving a competitive equilibrium between the heavy strand and the D-loop strand. This model suggests that frequent misalignment in the repeat region prior to elongation, facilitated by a stable secondary structure in the displaced strand, can explain both the polymorphism and heteroplasmy in this species. 相似文献