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91.
Connexin mutations in skin disease and hearing loss 总被引:8,自引:0,他引:8
92.
93.
Peptide chips for the quantitative evaluation of protein kinase activity 总被引:15,自引:0,他引:15
Peptide chips are an emerging technology that could replace many of the bioanalytical methods currently used in drug discovery, diagnostics, and cell biology. Despite the promise of these chips, their development for quantitative assays has been limited by several factors, including a lack of well-defined surface chemistries to immobilize peptides, the heterogeneous presentation of immobilized ligands, and nonspecific adsorption of protein to the substrate. This paper describes a peptide chip that overcomes these limitations, and demonstrates its utility in activity assays of the nonreceptor tyrosine kinase c-Src. The chip was prepared by the Diels-Alder-mediated immobilization of the kinase substrate AcIYGEFKKKC-NH(2) on a self-assembled monolayer of alkanethiolates on gold. Phosphorylation of the immobilized peptides was characterized by surface plasmon resonance, fluorescence, and phosphorimaging. Three inhibitors of the enzyme were quantitatively evaluated in an array format on a single, homogeneous substrate. 相似文献
94.
Howe GT; Bucciaglia PA; Hackett WP; Furnier GR; Cordonnier-Pratt MM; Gardner G 《Molecular biology and evolution》1998,15(2):160-175
The phytochrome photoreceptors play important roles in the photoperiodic
control of vegetative bud set, growth cessation, dormancy induction, and
cold-hardiness in trees. Interestingly, ecotypic differences in
photoperiodic responses are observed in many temperate- zone tree species.
Northern and southern ecotypes of black cottonwood (Populus trichocarpa
Torr. & Gray), for example, exhibit marked differences in the timing of
short-day-induced bud set and growth cessation, and these responses are
controlled by phytochrome. Therefore, as a first step toward determining
the molecular genetic basis of photoperiodic ecotypes in trees, we
characterized the phytochrome gene (PHY) family in black cottonwood. We
recovered fragments of one PHYA and two PHYB using PCR-based cloning and by
screening a genomic library. Results from Southern analyses confirmed that
black cottonwood has one PHYA locus and two PHYB loci, which we arbitrarily
designated PHYB1 and PHYB2. Phylogenetic analyses which included PHY from
black cottonwood, Arabidopsis thaliana and tomato (Solanum lycopersicum)
suggest that the PHYB/D duplications in these species occurred
independently. When Southern blots were probed with PHYC, PHYE, and PHYE
heterologous probes, the strongest bands that we detected were those of
black cottonwood PHYA and/or PHYB. These results suggest that black
cottonwood lacks members of the PHYC/F and PHYE subfamilies. Although black
cottonwood could contain additional PHY that are distantly related to known
angiosperm PHY, our results imply that the PHY family of black cottonwood
is less complex than that of other well-characterized dicot species such as
Arabidopsis and tomato. Based on Southern analyses of five black cottonwood
genotypes representing three photoperiodic ecotypes, substantial
polymorphism was detected for at least one of the PHYB loci but not for the
PHYA locus. The novel character of the PHY family in black cottonwood, as
well as the differences in polymorphism we observed between the PHYA and
PHYB subfamilies, indicates that a number of fundamental macro- and
microevolutionary questions remain to be answered about the PHY family in
dicots.
相似文献
95.
96.
Characterization of UVC light sensitivity of vaccinia virus 总被引:1,自引:0,他引:1
McDevitt JJ Lai KM Rudnick SN Houseman EA First MW Milton DK 《Applied and environmental microbiology》2007,73(18):5760-5766
Interest in airborne smallpox transmission has been renewed because of concerns regarding the potential use of smallpox virus as a biothreat agent. Air disinfection via upper-room 254-nm germicidal UV (UVC) light in public buildings may reduce the impact of primary agent releases, prevent secondary airborne transmission, and be effective prior to the time when public health authorities are aware of a smallpox outbreak. We characterized the susceptibility of vaccinia virus aerosols, as a surrogate for smallpox, to UVC light by using a benchtop, one-pass aerosol chamber. We evaluated virus susceptibility to UVC doses ranging from 0.1 to 3.2 J/m(2), three relative humidity (RH) levels (20%, 60%, and 80%), and suspensions of virus in either water or synthetic respiratory fluid. Dose-response plots show that vaccinia virus susceptibility increased with decreasing RH. These plots also show a significant nonlinear component and a poor fit when using a first-order decay model but show a reasonable fit when we assume that virus susceptibility follows a log-normal distribution. The overall effects of RH (P < 0.0001) and the suspending medium (P = 0.014) were statistically significant. When controlling for the suspending medium, the RH remained a significant factor (P < 0.0001) and the effect of the suspending medium was significant overall (P < 0.0001) after controlling for RH. Virus susceptibility did not appear to be a function of virus particle size. This work provides an essential scientific basis for the design of effective upper-room UVC installations for the prevention of airborne infection transmission of smallpox virus by characterizing the susceptibility of an important orthopoxvirus to UVC exposure. 相似文献
97.
Increasingly used in health-related applications, latent variable models provide an appealing framework for handling high-dimensional exposure and response data. Item response theory (IRT) models, which have gained widespread popularity, were originally developed for use in the context of educational testing, where extremely large sample sizes permitted the estimation of a moderate-to-large number of parameters. In the context of public health applications, smaller sample sizes preclude large parameter spaces. Therefore, we propose a penalized likelihood approach to reduce mean square error and improve numerical stability. We present a continuous family of models, indexed by a tuning parameter, that range between the Rasch model and the IRT model. The tuning parameter is selected by cross validation or approximations such as Akaike Information Criterion. While our approach can be placed easily in a Bayesian context, we find that our frequentist approach is more computationally efficient. We demonstrate our methodology on a study of methylation silencing of gene expression in bladder tumors. We obtain similar results using both frequentist and Bayesian approaches, although the frequentist approach is less computationally demanding. In particular, we find high correlation of methylation silencing among 16 loci in bladder tumors, that methylation is associated with smoking and also with patient survival. 相似文献
98.
James J. McDevitt Ka Man Lai Stephen N. Rudnick E. Andres Houseman Melvin W. First Donald K. Milton 《Applied microbiology》2007,73(18):5760-5766
Interest in airborne smallpox transmission has been renewed because of concerns regarding the potential use of smallpox virus as a biothreat agent. Air disinfection via upper-room 254-nm germicidal UV (UVC) light in public buildings may reduce the impact of primary agent releases, prevent secondary airborne transmission, and be effective prior to the time when public health authorities are aware of a smallpox outbreak. We characterized the susceptibility of vaccinia virus aerosols, as a surrogate for smallpox, to UVC light by using a benchtop, one-pass aerosol chamber. We evaluated virus susceptibility to UVC doses ranging from 0.1 to 3.2 J/m2, three relative humidity (RH) levels (20%, 60%, and 80%), and suspensions of virus in either water or synthetic respiratory fluid. Dose-response plots show that vaccinia virus susceptibility increased with decreasing RH. These plots also show a significant nonlinear component and a poor fit when using a first-order decay model but show a reasonable fit when we assume that virus susceptibility follows a log-normal distribution. The overall effects of RH (P < 0.0001) and the suspending medium (P = 0.014) were statistically significant. When controlling for the suspending medium, the RH remained a significant factor (P < 0.0001) and the effect of the suspending medium was significant overall (P < 0.0001) after controlling for RH. Virus susceptibility did not appear to be a function of virus particle size. This work provides an essential scientific basis for the design of effective upper-room UVC installations for the prevention of airborne infection transmission of smallpox virus by characterizing the susceptibility of an important orthopoxvirus to UVC exposure. 相似文献
99.
Heather H. Nelson Carmen J. Marsit Brock C. Christensen E.A. Houseman Milica Kontic Joseph L. Wiemels Margaret R. Karagas Margaret R. Wrensch Shichun Zheng John K. Wiencke Karl T. Kelsey 《Epigenetics》2012,7(6):559-566
Epigenetic alterations are a common event in lung cancer and their identification can serve to inform on the carcinogenic process and provide clinically relevant biomarkers. Using paired tumor and non-tumor lung tissues from 146 individuals from three independent populations we sought to identify common changes in DNA methylation associated with the development of non-small cell lung cancer. Pathologically normal lung tissue taken at the time of cancer resection was matched to tumorous lung tissue and together were probed for methylation using Illumina GoldenGate arrays in the discovery set (n = 47 pairs) followed by bisulfite pyrosequencing for validation sets (n = 99 pairs). For each matched pair the change in methylation at each CpG was calculated (the odds ratio), and these ratios were averaged across individuals and ranked by magnitude to identify the CpGs with the greatest change in methylation associated with tumor development. We identified the top gene-loci representing an increase in methylation (HOXA9, 10.3-fold and SOX1, 5.9-fold) and decrease in methylation (DDR1, 8.1-fold). In replication testing sets, methylation was higher in tumors for HOXA9 (p < 2.2 × 10−16) and SOX1 (p < 2.2 × 10−16) and lower for DDR1 (p < 2.2 × 10−16). The magnitude and strength of these changes were consistent across squamous cell and adenocarcinoma tumors. Our data indicate that the identified genes consistently have altered methylation in lung tumors. Our identified genes should be included in translational studies that aim to develop screening for early disease detection. 相似文献
100.