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T J Ward

Publications and source records attributed to T J Ward.

At least 19 recordsLinked to original sources

Chromosome complement of the fungal plant pathogen Fusarium graminearum based on genetic and physical mapping and cytological observations.

A genetic map of the filamentous fungus Fusarium graminearum (teleomorph: Gibberella zeae) was constructed to both validate and augment the draft whole-genome sequence assembly of strain PH-1. A mapping population was created from a cross between mutants of the sequenced strain (PH-1, NRRL 31084, originally isolated from Michigan) and a field strain from Minnesota (00-676, NRRL 34097). A total of 111 ascospore progeny were analyzed for segregation at 235 loci. Genetic markers consisted of sequence-tagged sites, primarily detected as dCAPS or CAPS (n = 131) and VNTRs (n = 31), in addition to AFLPs (n = 66) and 7 other markers. While most markers exhibited Mendelian inheritance, segregation distortion was observed for 25 predominantly clustered markers. A linkage map was generated using the Kosambi mapping function, using a LOD threshold value of 3.5. Nine linkage groups were detected, covering 1234 cM and anchoring 99.83% of the draft sequence assembly. The nine linkage groups and the 22 anchored scaffolds from the sequence assembly could be assembled into four chromosomes, leaving only five smaller scaffolds (59,630 bp total) of the nuclear DNA unanchored. A chromosome number of four was confirmed by cytological karyotyping. Further analysis of the genetic map data identified variation in recombination rate in different genomic regions that often spanned several hundred kilobases.

Chromosome Segregation↗

Synergistic chiral separations using the glycopeptides ristocetin A and vancomycin.

The effectiveness of using a mixture of the chiral selectors vancomycin and ristocetin A to achieve chiral recognition was examined in this study. The results of using the mixed chiral selector vancomycin and ristocetin A in capillary electrophoresis were compared with the results of using each chiral selector alone. Chiral separations were carried out using a coated capillary column to suppress electroosmotic flow and minimize interactions with the capillary wall. We employed a countercurrent process where the solute reaches the detection cell window after the chiral selector has cleared the window, minimizing the background absorbance from the chiral selector and improving sensitivity. Using a mixture of vancomycin and ristocetin A, separations were achieved which often exceeded the resolving power of either chiral selector when used alone. The effect of voltage on resolution was also studied, and the optimal voltage was found to be between -5 and -8 kV.

Anti-Bacterial Agents↗

Chiral separations using the macrocyclic antibiotics: a review.

The macrocyclic antibiotics have recently gained popularity as chiral selectors in CE, HPLC and TLC. The macrocyclic antibiotics used for chiral separations include the ansamycins, the glycopeptides, and the polypeptide antibiotic thiostrepton. Although not strictly considered macrocyclic antibiotics, the aminoglycosides are antibiotics that have been used for chiral separations in CE. More chiral analytes have been resolved using the glycopeptides than with the other macrocyclic antibiotics combined. The glycopeptides vancomycin, ristocetin A and teicoplanin have been used extensively as chiral selectors in CE, with ristocetin A appearing to be the most useful chiral selector followed by vancomycin and teicoplanin, respectively. The macrocyclic antibiotics have also been used as chiral bonded phases in HPLC, and HPLC stationary phases based on vancomycin, ristocetin A and teicoplanin have been commercialized. Ristocetin A seems to be the most useful glycopeptide HPLC bonded phase, but its greater expense can be a drawback. The macrocyclic antibiotics have been used with micelles to improve efficiency, provide unique selectivity, and extend the range of separations to neutral solutes. Changing the macrocyclic antibiotic used in CE or HPLC can significantly alter the enantioselectivity of the separations. In fact, the glycopeptide antibiotics are complementary to one another, where if a partial enantioresolution is obtained with one glycopeptide, there is a high probability that a baseline or better separation can be obtained with another.

Anti-Bacterial Agents↗

Differential introgression of uniparentally inherited markers in bison populations with hybrid ancestries.

Historical hybridization between Bison bison (bison) and Bos taurus (cattle) has been well documented and resulted in cattle mitochondrial DNA (mtDNA) introgression, previously identified in six different bison populations. In order to examine Y chromosome introgression, a microsatellite marker (BYM-1) with non-overlapping allele size distributions in bison and cattle was isolated from a bacterial artificial chromosome (BAC) clone, and was physically assigned to the Y chromosome by fluorescence in situ hybridization. BYM-1 genotypes for a sample of 143 male bison from 10 populations, including all six populations where cattle mtDNA haplotypes were previously identified, indicated that cattle Y chromosome introgression had not occurred in these bison populations. The differential permeability of uniparentally inherited markers to introgression is consistent with observations of sterility among first generation hybrid males and a sexual asymmetry in the direction of hybridization favouring matings between male bison and female cattle.

Animals↗

Chiral separations.

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Chromatography, Gas↗

Validation of 15 microsatellites for parentage testing in North American bison, Bison bison and domestic cattle.

Fifteen bovine microsatellites were evaluated for use in parentage testing in 725 bison from 14 public populations, 178 bison from two private ranches and 107 domestic cattle from five different breeds. The number of alleles per locus ranged from five to 16 in bison and from five to 13 in cattle. On average, expected heterozygosity, polymorphism information content (PIC) and probability of exclusion values were slightly lower in bison than in cattle. A core set of 12 loci was further refined to produce a set of multiplexed markers suitable for routine parentage testing. Assuming one known parent, the core set of markers provides exclusion probabilities in bison of 0.9955 and in cattle of 0.9995 averaged across all populations or breeds tested. Tests of Hardy-Weinberg and linkage equilibrium showed only minor deviations. This core set of 12 loci represent a powerful and efficient method for determining parentage in North American bison and domestic cattle.

Animals↗

Enantioseparations with the macrocyclic antibiotic ristocetin A using a countercurrent process in CE.

The chiral selectivity of ristocetin A was examined in a countercurrent process in CE using a coated column to suppress electroosmotic flow. Excellent enantioseparations of several nonsteroidal antiinflammatories, dansylamino acids, dinitrophenyl-derivatized amino acids, and other optically active compounds were achieved. The chiral selectivity of ristocetin A also was examined as a function of antibiotic concentration and pH. Enantioresolution was found to significantly improve with a slight increase in migration time upon increasing chiral selector concentration. Enantioselectivities were found to be greatly influenced by pH of the running buffer.

Anti-Bacterial Agents↗

Enantioselectivity in capillary electrophoresis using the macrocyclic antibiotics.

The macrocyclic antibiotics recently have been shown to exhibit powerful enantioselectivity towards numerous compounds. There are a number of ways that one can alter enantioselectivity in the macrocyclic antibiotic-based separation schemes. The macrocyclic antibiotics are enantioselective for positively-charged solutes using the ansamycins and enantioselective for anionic compounds using the glycopeptides. Within a given class of antibiotics such as the glycopeptides, enantioselectivity may also be altered by use of micelles, uncoated vs. coated capillaries, or manipulation of operating parameters such as pH or organic modifiers. In this work, we will examine the various ways to alter enantioselectivity in the macrocyclic-based separations.

Anti-Bacterial Agents↗

Nucleotide sequence evolution at the kappa-casein locus: evidence for positive selection within the family Bovidae.

Kappa-casein is a mammalian milk protein involved in a number of important physiological processes. In the gut, the ingested protein is split into an insoluble peptide (para kappa-casein) and a soluble hydrophilic glycopeptide (caseinomacropeptide). Caseinomacropeptide is responsible for increased efficiency of digestion, prevention of neonate hypersensitivity to ingested proteins, and inhibition of gastric pathogens. Variation within this peptide has significant effects associated with important traits such as milk production. The nucleotide sequences for regions of kappa-casein exon and intron four were determined for representatives of the artiodactyl family Bovidae. The pattern of nucleotide substitution in kappa-casein sequences for distantly related bovid taxa demonstrates that positive selection has accelerated their divergence at the amino acid sequence level. This selection has differentially influenced the molecular evolution of the two kappa-casein split peptides and is focused within a 34-codon region of caseinomacropeptide.

Animals↗

Enantiomeric resolution using the macrocyclic antibiotics rifamycin B and rifamycin SV as chiral selectors for capillary electrophoresis.

Rifamycin B and rifamycin SV belong to the class of macrocyclic antibiotics known as ansamycins. These macrocyclic antibiotics were used as chiral selectors in capillary electrophoresis to enantioselectively resolve a number of chiral compounds. They contain groups capable of providing the types of multiple interactions necessary to achieve chiral recognition between enantiomers. In fact, they appear to be complimentary in the types of compounds they can enantiomerically resolve. Rifamycin B is shown to be enantioselective towards positively charged compounds, while rifamycin SV was enantioselective towards negatively charged solutes. The choice of wavelength for detection significantly affects sensitivity. Monitoring one of the wavelengths which coincide with the absorption minima of the chiral selector enhances sensitivity. Resolution is enhanced by keeping the amount of analyte injected on column as low as possible and it is demonstrated that it is possible to detect as little as 0.1% of one enantiomer in the presence of the other enantiomer using indirect detection.

Anti-Bacterial Agents↗

An evaluation of the aquatic hazard of cumene (isopropyl benzene).

Cumene manufacturers were required under a TSCA Section 4(a) test rule to evaluate the aquatic toxicity of cumene to daphnids, rainbow trout, mysid shrimp, and sheepshead minnows. Because of cumene's high volatility (vapor pressure, 3.2 mm Hg at 20 degrees C), all tests were conducted under flowthrough conditions using a proportional diluter system. The 96-hr LC50s for rainbow trout, sheepshead minnow, and mysid shrimp, based on mean measured concentrations, were 4.8, 4.7, and 1.3 mg/liter, respectively. The 48-hr daphnid EC50 was 4.0 mg/liter. Although cumene is considered moderately toxic to aquatic organisms under rigorous laboratory conditions, its volatility and biodegradability greatly reduce its hazard to the aquatic environment.

Animals↗

Hospital admissions and social deprivation of patients with diabetes mellitus.

This study examined the relationship between hospital admissions for patients with diabetes mellitus and residence in an area of social deprivation. Admissions of patients with diabetes mellitus were identified during a 5-year period between 1987 and 1992 using the district patient information service. All persons admitted were assigned to an electoral ward on the basis of their postcode. Age standardized admission rates were compared to the Townsend Deprivation Score for each electoral ward. A positive correlation was found between age standardized admission rate and Townsend Score (r = 0.76, p < 0.001). We believe this has significance for planning health care resources.

Diabetes Mellitus↗

Novel antagonists of the 5-HT3 receptor. Synthesis and structure-activity relationships of (2-alkoxybenzoyl)ureas.

A series of benzoylureas derived from bicycle amines were prepared and evaluated for 5-HT3 antagonist activity on the rat isolated vagus nerve. From among these compounds, those analogues which were ortho substituted by an alkoxy group on the benzoyl function were shown to be potent 5-HT3 antagonists with similar or greater potency than the standard agent ondansetron. NMR and X-ray crystallography studies showed these o-alkoxy compounds to exist as a planar, hydrogen-bonded, tricyclic ring system. In molecular modeling studies on endo-N-[[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl-amino] carbonyl]-2-(cyclopropylmethoxy)benzamide (30) the central hydrogen-bonded ring was able to mimic an aromatic ring present in previously reported 5-HT3 antagonists.

Animals↗

Design of an antithrombotic-antihypertensive agent (Wy 27569). Synthesis and evaluation of a series of 2-heteroaryl-substituted dihydropyridines.

An approach to the design of potential combined antithrombotic-antihypertensive agents is described. A series of 1,4-dihydropyridines bearing a 1H-imidazol-1-yl or pyrid-3-yl substituted side chain in the 2-position were synthesized and tested for antihypertensive activity in spontaneously hypertensive rats and for inhibition of TXA2 synthetase in rabbit platelets, in vitro. 1,4-Dihydro-2-(1H-imidazol-1-ylmethyl)-6-methyl- 4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid 3-ethyl 5-methyl diester (1) was shown to be similar in potency to nitrendipine as an antihypertensive agent. Compound 1 inhibited TXA2 synthetase in rabbit and human platelets in vitro and reduced plasma TXB2 levels in rats at antihypertensive dose levels. The reductions in thromboxane production observed in vivo and in vitro were accompanied by enhanced levels of 6-KPGF1 alpha, reflecting diversion of the arachidonic acid cascade toward prostacyclin synthesis.

6-Ketoprostaglandin F1 alpha↗

Synthesis and alpha 2-adrenoceptor antagonist activity of some disulfonamidobenzoquinolizines.

A series of disulfonamidobenzo[a]quinolizines were synthesized and evaluated for their alpha 2- and alpha 1-adrenoceptor antagonist activity on the rat vas deferens and anococcygeus muscle, respectively. N-((2 beta,11b alpha)-1,3,4,6,7,11b-Hexahydro-2H-benzo[a]quinolizin-2-yl)-N- [2-[(methylsulfonyl)amino]ethyl]methanesulfonamide (4) and its N-[2-[(methylsulfonyl)amino]ethyl]ethanesulfonamide (22), N-[2-[(ethylsulfonyl)amino]ethyl]ethanesulfonamide (27), and N-[2-[(methylsulfonyl)amino]ethyl]-4-methylbenzenesulfonamide (30) analogues showed 400-fold or greater selectivity in favor of alpha 2- over alpha 1-adrenoceptor blockade.

Adrenergic alpha-Antagonists↗