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91.
The accurate prediction of T cell epitopes is one of the key aspirations of immunoinformatics. We have developed a partial least squares-based, robust multivariate statistical method for the quantitative prediction of peptide binding to major histocompatibility complexes (MHCs), the principal checkpoint on the antigen presentation pathway. As a service to the immunobiology community, we have made a Perl implementation of the method available as a World Wide Web server. 相似文献
92.
The mechanisms of molecular discrimination by connexin channels are of acute biological and medical importance. The availability of affinity or open-pore blocking reagents for reliable and specific study of the connexin permeability pathway, would make possible the rigorous cellular and physiological studies required to inform, in molecular terms, the underlying role of intercellular communication pathways in development and disease. Previous work utilized a series of glucosaccharides labeled with an uncharged fluorescent aminopyridine (PA-) group to establish steric constraints to permeability through connexin hemichannels. In that work, the smallest probe permeable through homomeric Cx26 and heteromeric Cx26-Cx32 channels was the PA-disaccharide, and the smallest probe permeable through homomeric Cx32 channels was the PA-trisaccharide. The larger impermeable probes did not block permeation of the smaller probes. Building on this work, a new set of glucosaccharide probes was developed in which the label was one of a homologous series of novel anthranilic acid derivatives (ABG) that carry negative or positive formal charge or remain neutral at physiological pH. When the PA-label of the smallest impermeant PA-derivatized oligosaccharides was replaced by ABG label, the resulting probes acted as reversible, high-affinity inhibitors of large molecule permeation through connexin pores in a size and connexin-specific manner. 相似文献
93.
Roberts D Okimoto DK Parsons C Straume M Stetson MH 《Journal of experimental zoology. Part A, Comparative experimental biology》2003,296(1):56-62
The pineal gland of vertebrates produces and secretes the hormone melatonin in response to changes in the light-dark cycle, with high production at night and low production during the day. Melatonin is thought to play an important role in synchronizing daily and/or seasonal physiological, behavioral, and developmental rhythms in vertebrates. In this study, the functional development of the pineal melatonin-generating system was examined in the mummichog, Fundulus heteroclitus, an euryhaline teleost. In this species, the pineal gland contains an endogenous oscillator, ultimately responsible for timing the melatonin rhythm. Oocytes from gravid females were collected and fertilized in vitro from sperm collected from mature males. Skull caps containing attached pineal glands were obtained from F. heteroclitus embryos at different embryonic stages and placed in static or perfusion culture under various photoperiodic regimes. Rhythmic melatonin secretion from pineal glands of embryonic F. heteroclitus embryos exposed to a 12L:12D cycle in static culture was observed at five days post-fertilization. The ontogeny of circadian-controlled melatonin production from F. heteroclitus pineal glands exposed to constant darkness for five days was also seen at day five post-fertilization. These data show that early development of the pineal melatonin-generating system in this teleost occurs prior to hatching. Pre-hatching development of the melatonin-generating system may confer some selective advantage in this species in its interactions with the environment. 相似文献
94.
95.
Saraswat LD Caserta KA Laws K Wei D Jones SS Adedoyin A 《Journal of biomolecular screening》2003,8(5):544-554
A simple and flexible setup for conducting drug metabolism studies is described in this report. A heating block was designed for the Multimek liquid handler platform for incubation of multiple samples at 37 degrees C in a 96-well format. This setup enables the rapid performance of drug metabolism experiments on a large number of samples. In this report, the authors present the validation of the system by 1) showing reproducible and consistent determination of the in vitro half-life of midazolam in every well across the entire plate and 2) determination of metabolic parameter values of midazolam, testosterone, diclofenac, warfarin, and dextromethorphan and inhibition parameter values of quinidine and ketoconazole, all comparable to literature values. In addition, the authors demonstrate the application of the setup to determining the metabolic stability of a set of proprietary compounds, the inhibition of activity of cytochrome P450 (CYP) enzymes, and the conduct of a single combination experiment that can simultaneously determine the metabolic stability and CYP inhibition activity. Overall, the system represents a simple, high-throughput and useful tool for drug metabolism screening in drug discovery. 相似文献
96.
Kirkwood TB Boys RJ Gillespie CS Proctor CJ Shanley DP Wilkinson DJ 《Nature reviews. Molecular cell biology》2003,4(3):243-249
Ageing is a highly complex process; it involves interactions between numerous biochemical and cellular mechanisms that affect many tissues in an organism. Although work on the biology of ageing is now advancing quickly, this inherent complexity means that information remains highly fragmented. We describe how a new web-based modelling initiative is seeking to integrate data and hypotheses from diverse biological sources. 相似文献
97.
A relational database for the discovery of genes encoding amino acid biosynthetic enzymes in pathogenic fungi 总被引:2,自引:0,他引:2
Fungal phytopathogens continue to cause major economic impact, either directly, through crop losses, or due to the costs of fungicide application. Attempts to understand these organisms are hampered by a lack of fungal genome sequence data. A need exists, however, to develop specific bioinformatics tools to collate and analyse the sequence data that currently is available. A web-accessible gene discovery database (http://cogeme.ex.ac.uk/biosynthesis.html) was developed as a demonstration tool for the analysis of metabolic and signal transduction pathways in pathogenic fungi using incomplete gene inventories. Using Bayesian probability to analyse the currently available gene information from pathogenic fungi, we provide evidence that the obligate pathogen Blumeria graminis possesses all amino acid biosynthetic pathways found in free-living fungi, such as Saccharomyces cerevisiae. Phylogenetic analysis was also used to deduce a gene history of succinate-semialdehyde dehydrogenase, an enzyme in the glutamate and lysine biosynthesis pathways. The database provides a tool and methodology to researchers to direct experimentation towards predicting pathway conservation in pathogenic microorganisms. 相似文献
98.
Sturm RA Duffy DL Box NF Chen W Smit DJ Brown DL Stow JL Leonard JH Martin NG 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2003,16(3):266-272
We have examined melanocortin-1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32-140) or weak r (OR = 5; 95% CI 3-11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild-type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk. 相似文献
99.
Natale DA Shankavaram UT Galperin MY Wolf YI Aravind L Koonin EV 《Genome biology》2000,1(5):research0009.1-research000919
Background
Standard archival sequence databases have not been designed as tools for genome annotation and are far from being optimal for this purpose. We used the database of Clusters of Orthologous Groups of proteins (COGs) to reannotate the genomes of two archaea, Aeropyrum pernix, the first member of the Crenarchaea to be sequenced, and Pyrococcus abyssi. 相似文献100.
Paddy Kane Kevin Kincaid Darren Fayne Dermot Diamond M. Anthony McKervey 《Journal of molecular modeling》2000,6(2):272-281
This paper focuses on the molecular modelling of a number of calixarene ester and phosphine oxide metal ion complexes. Monte Carlo conformational searches, in conjunction with the Merck Molecular Force Field, were carried out using Spartan SGI Version 5.0.1. running on Silicon Graphics O2 workstations. In the case of the calix[4]arene tetraesters, the optimised models strongly suggest that the selectivity of these ligands is strongly related to the eight-fold nature of the coordination with the Na+ ion, while coordination with the Li+ ion, for example, is merely three-fold. This feature of eight-fold coordination is also observed in the models of the complexes formed by the calix[4]arene tetraphosphine oxides with calcium. However, whereas the eight-fold coordination is unique to the model of the TPOL:Ca2+ complex among the ions modelled, this mode of coordination occurs for TPOS with sodium and potassium, in addition to calcium. This concurs with the observation that calcium selectivity is obtained with ion selective electrodes based on TPOL but not TPOS. Though the cavity in the calix[5]arenes PPOL and PPOLx and the calix[6]arene HPOL, in their uncomplexed form, are much larger than that of the corresponding calix[4]arenes, the pattern of selectivity is the same – the ligands are selective for calcium. The models of the complexes of these larger calixarenes, such as PPOL:Ca2+, strongly suggest that the reason for this similarity is that four of the available phosphine oxide groups complex with the calcium ion, and the others are forced away from the cavity region for steric reasons. The resulting eight-fold coordination, is therefore, similar to that of the calix[4]arenes studied.Electronic Supplementary Material available. 相似文献