Thesis (doctoral)--Rijksuniversiteit te Utrecht, 1980. / Dutch summary. Includes vita. Includes bibliographical references.

A quantitative trait locus (QTL) is the location of a gene that affects a trait that is measured on a quantitative (linear) scale. Many important agricultural traits such as weight gain, milk fat content and intramuscular fat in cattle are quantitative traits. There is a need to integrate genomic sequence data with QTL data and to develop an analytical tool to visualize the data. Without integration, application of this data to agricultural enterprise productivity will be slow and inefficient. My thesis presents a web-accessible tool called the Bovine QTL Viewer developed to solve this problem. It consists of an integrated database of bovine QTL and the QTL viewer to view the QTL and their relative chromosomal position. This tool generates dynamic and interactive images and supports research in the field of genomics. For this tool, the data is modeled and the QTL viewer is developed based on the requirements and feedback of experts in the field of bovine genomics.

Résumé Létude des performances laitières des bovins en stations au Burundi a été réalisée dans les stations de Mahwa et de Rukoko de lInstitut des Sciences Agronomiques du Burundi (ISABU). Elle a pour objectifs principaux de quantifier les effets des facteurs non génétiques et de croisement sur la production laitière journalière et de prédire les paramètres génétiques et de croisement de la production laitière journalière des bovins de ces stations. Elle a également pour objectifs secondaires de décrire lélevage bovin laitier au Burundi et de proposer des perspectives et solutions damélioration de cette activité. 1.Elevage bovin laitier au Burundi Lélevage bovin laitier au Burundi est limité par plusieurs contraintes dont les principales sont la diminution des pâturages en raison de la croissance continue de la population, la présence de diverses pathologies animales incontrôlées, linsuffisance des structures publiques ou privées destinées à promouvoir lélevage laitier et à améliorer la génétique bovine, le manque de formation pratique des éleveurs burundais et labsence dune filière lait. Ces conditions défavorables ont été accentuées par la guerre de 1993 qui a entraîné une diminution des effectifs bovins, la réduction de la quantité du lait déjà déficitaire ainsi que la suspension des activités des projets délevage bovin entre autre dans les stations de lISABU. 2.Influence des facteurs environnementaux et du croisement sur la production laitière journalière. La production laitière des bovins des stations de lISABU est influencée par différents facteurs dont la durée de lactation, lâge au vêlage, la parité, le type de croisement entre bovins, le mode dallaitement des veaux, lannée et la saison de lactation. Ces effets ont été quantifiés à laide dun modèle linéaire permettant destimer les moyennes des moindres carrés de la production laitière journalière pour chaque facteur. Les résultas de ces analyses montrent que la production laitière journalière était plus élevée en saison des pluies quen saison sèche. Les meilleures productions ont été observées chez les bovins croisés avec 50 à 75% Bos taurus (Ayrshire et Jersey). La guerre de 1993 a provoqué une chute de production laitière journalière de 53,14% (en moyenne) qui serait due à linsuffisance des moyens financiers pour assurer un niveau alimentaire et un suivi vétérinaire suffisants. Cette détérioration des conditions délevage est à lorigine des faibles performances laitières observées dans les stations de lISABU. Pour les bovins Ayrshire x Sahiwal x Ankole, le maximum de production laitière journalière a été observé au 8ème jour (7,16 ± 0,07 l/jour) de lactation chez 150 vaches allaitées et traites pendant les 120 premiers jours (avant le sevrage) et traites ensuite (vaches AT). Il a été observé au 8ème jour (7,63 ± 0,39 l/jour) chez 8 bovins allaités et traits pendant toute la lactation (vaches A) et au 7ème jour (7,34 ± 0,39 l/jour) pour 7 bovins uniquement traits (vaches T). Ladéquation à la fonction de Wood (1976) des courbes de lactation a été vérifiée chez les bovins AT et T mais pas chez les animaux A. Chez les frisonnes, la courbe de lactation était normale avec un pic de lactation au 15ème jour de lactation (11,48 ± 0,20 l/jour). La courbe de lactation des croisées Jersey x Sahiwal x Ankole nétait pas normale. Le maximum de production laitière journalière (12,67 ± 0,42 l/jour) a été observé au 43ème jour de lactation. La production était plus élevée chez les bovins A que chez les bovins T. Une chute de production laitière autour de 120 premiers jours de lactation (période de sevrage) a été observée chez les bovins AT. Les meilleures productions laitières journalières ont étés observées chez les Ayrshire x Sahiwal x Ankole qui ont vêlé en première parité à un âge moyen de 31 mois (6,30 ± 0,15 l), en deuxième parité à un âge moyen de 49 mois (6,25 ± 0,10 l) et en troisième parité et plus à un âge moyen de 66 mois (4,62 ± 0,05 l). Chez les Frisonnes, la production laitière a augmenté avec lâge au vêlage en première et troisième et plus parité mais a évolué de manière curvilinéaire descendante avec un maximum de production laitière à lâge au vêlage de 44 mois en deuxième parité. La production laitière moyenne a été de 11,47 ± 0,30 l/jour, 5,23 ± 0,09 l/jour et de 10,11 ± 0,06 l/jour pendant respectivement la première, la deuxième et la troisième et plus lactation. 3.Paramètres génétiques et de croisement Les paramètres génétiques et de croisement pour la production laitière journalière des bovins Ayrshire x Sahiwal x Ankole ont été obtenus à laide dun modèle animal mixte répétable contenant les effets fixes : année (n = 26) et mois (n = 12) de lactation, semaines de lactation (n = 43) et mode dallaitement (n = 3), âge au vélage (n = 93) et parité (n = 3), groupe génétique (n = 5) ; les effets aléatoires génétiques additifs directs (n = 317) et les effets aléatoire liés à lenvironnement permanent (n = 184). La méthode du maximum de vraisemblance a été utilisée avec le programme de Misztal(1990) pour calculer les variances additive, environnementale et résiduelle. Les solutions des différents groupes génétiques ont été utilisées pour estimer les paramètres de croisement à laide du modèle de Dickerson (1969). Lhéritabilité et la répétabilité prédites étaient de 0.27 et 0.36, respectivement. La valeur prédite de leffet génétique additif direct pour la production laitière journalière de lAyrshire (5,22 l/jour) était positive et supérieure en valeur absolue à celles obtenues pour les races Sahiwal (-0,48 l/jour) et Ankole (-1,66 l/jour). Ces valeurs indiquent que la race Ayrshire contribue beaucoup à laugmentation de la production laitière journalière chez les bovins Ayrshire x Sahiwal x Ankole. Les valeurs estimées de lhétérosis direct pour la production laitière journalière des croisés Sahiwal x Ankole, Ayrshire x Ankole et Ayrshire x Sahiwal étaient respectivement de 1,97l/jour (35,8%), de 2,30 l/jour (41,9%) et de -2,33 l/jour (- 42,4%). Le pourcentage de lhétérosis direct des croisés Ayrshire x Ankole (41,9%) supérieur à celui des croisés Sahiwal x Ankole (35,8%) prouve quil serait plus productif de croiser lAnkole avec lAyrshire si les conditions délevage étaient améliorées. SUMMARY The current study was conducted on the Mahwa and Rukoko stations of the Institute of agronomic Sciences in Burundi (ISABU). The aim of the study was to assess the effects of environmental and crossbreeding factors on the daily milk yield (DMY) and to predict genetic and crossbreeding parameters for DMY of cows in those stations. The secondary objectives were to describe the dairy breeding in Burundi and to propose solutions of improvement of milk production in the country. 1. Dairy cattle breeding in Burundi In Burundi, dairy cattle breeding is limited by many constraints of which the principal are the low level of feeding, the presence of many and uncontrolled animal diseases, the lack of public and private institutions to help smallholders, the limited know-how of smallholders and the lack of milk market and conditioning equipments in rural area. The 1993 crisis accentuated the situation and caused the decrease of the dairy cattle population and disturbed breeding activities in ISABU stations and in other breeding projects. 2. Effects of non genetic and crossbreeding factors on the daily milk yield of cows in the stations Lactation length and suckling, calving age and parity, genetic groups, month and years of lactation were the principal factors that affected DMY of cows in the ISABU stations. A linear model was used to quantify effects of those factors on DMY. All factors influenced significantly (P<0.001) DMY. Milk production was significantly higher during the rainy than the dry season. Crossbreeding improved milk production and highest yields were observed with 50% to 75% of Bos Taurus (Ayrshire or Jersey) inheritance. Milk production increased from 1977 to 1992 due to the improvement of genetic and the interaction of environmental and animal management. The decrease observed since 1993 in all cows was related to the civilian war which caused financial problems in the ISABU institution, decline in feeding and deterioration of the animal health. This situation was also responsible of the low milk production observed in the stations. For Ayrshire x Sahiwal x Ankole cows, the maximum of DMY was observed at 8th (7.16 ± 0.07 l/day), 8th (7.63 ± 0.39 l/day) and 7th day in milk (7,34 ± 0,39 l/ day) for suckled and milked (SM), suckled only (S) and milked only (M) cows. The incomplete gamma model using the Wood function was able to distinguish two groups of milk curve: standard shape for the M and SM cows and an atypical continuously decreasing shape for the S cows. For Friesian purebred cows, the lactation shape was typical and the maximum of DMY (11.48 ± 0.20 l/ day) was observed at 15th day in milk. The lactation shape for Jersey x Sahiwal x Ankole crossed cows was in disagreement with the theoretical curve and the maximum DMY (12.67 ± 0.42 l/ day) was observed at 43rd day in milk. Milk production was higher in SM cows than in M cows. For SM cows, a drop was observed at 120th day in milk corresponding to the weaning period. For Ayrshire x Sahiwal x Ankole crosses cows, highest least-squares means were observed at calving ages of 31 months (6.30 ± 0.15 l), 49 months (6.25 ± 0.10 l) and 66 months (4.62 ± 0.05 l) for SM cows in parities 1, 2 and 3 or more, respectively. For Friesian cows, milk production increased with the calving age in the 1st and 3rd and more parities. In the 2nd parity, the trend was curvilinear decreasing with the maximum production at the 44th month of age at calving. 3. Prediction of genetic and crossbreeding parameters for DMY of Ayrshire x Sahiwal x Ankole crosses cows The prediction of heritability, repeatability and crossbreeding parameters was only possible in the Ayrshire x Sahiwal x Ankole crosses cows due to the limited number of cows in the other groups. Data were analysed using an animal model that included year and month of lactation, age at calving, parity, suckling group, week in milk and genetic groups as fixed effects and the random effects for the direct additive genetic and the permanent environmental effects. The programs of Miztal (1990) were used to obtain REML estimates of the additive, environmental and residual variances. Solutions obtained for the genetic groups with the animal model were used to compute the crossbreeding parameters following Dickersons genetic model (1969). The overall average DMY was 5.49 l/day. Computed heritability and repeatability were 0.27 and 0.36, respectively. The predicted additive direct effects for DMY of Ankole (A), Sahiwal (S) and Ayrshire (A) breeds were -1.66 l, -0.48 l and 5.22 l, respectively. These values indicated that the Ayrshire breed contributed most to the increase in DMY of the Ayrshire x Sahiwal x Ankole crosses in the Mahwa station. The estimated direct heterosis effects for DMY of SA, YS and YA crosses were 1.97 l (35,8%), -2.33 l(- 42,4%) and 2.30 l (41,9%), respectively. Direct heterosis for YA was higher than that for SA crosses because A and Y cows are more different in their gene frequency than A and S cows. These values suggested that it is more productive to cross Ankole with Ayrshire (Bos Taurus) than with Sahiwal (Bos Indicus).

Embryonic stem cells are pluripotent cells isolated from morula stage embryos or the inner cell mass of blastocyst stage embryos. They are capable of differentiating into tissues of all three primary germ layers. In recent years pluripotent cell lines have been created from somatic cell types using various methods, the primary method being viral transduction of exogenous Oct4, Sox2, Klf4, and c-Myc or Oct4, Sox2, Nanog, and Lin28 transgene constructs. The resulting cell lines are termed induced pluripotency stem cells, and are similar to embryonic stem cells in many ways. However, these cell lines are not acceptable for clinical applications due to the use of both modified viral vectors and insertion of exogenous transgenes in their production. Recently the small molecule RepSox, a TGF-ß pathway inhibitor, was used to replace Sox2 during cellular reprogramming of murine embryonic fibroblasts. We evaluated the effects of RepSox on expression of pathways related to pluripotency in murine embryonic fibroblast, murine embryonic stem, and bovine embryonic fibroblast cells. Each cell type was treated with RepSox for 72 hours and subjected to standard qPCR for gene expression analysis. PCR arrays specific to stem cell pathways were used to initially evaluate the effects of RepSox on candidate genes. A subset of genes was then selected for further analysis based on these initial results. We report that RepSox inhibition of the TGF-ß pathway in murine embryonic fibroblasts results in significant upregulation of components of the Wnt, Notch, and Hedgehog signaling pathways, all of which have been linked to stem cell maintenance. In addition, we observed significant upregulation of genes associated with embryonic, mesenchymal, stem cell, and neural cell lineages, indicating that RepSox may be useful in direct reprogramming of murine cells to other somatic cell types. RepSox treatment of murine embryonic stem cells did not result in consistent upregulation of Wnt, Notch, or Hedgehog pathway components, but did result in upregulation of Sox2 and Klf4 expression. Lastly, RepSox treatment of bovine embryonic fibroblasts did not result in the same effects as seen in murine fibroblasts, indicating a need for further analysis to determine the effects of RepSox on bovine cells.

No description available.

Vaccination has proven a cost-effective method of managing infectious diseases, but attempts to develop an effective fetal vaccine have proven difficult due to the immaturity of the immune system and the propensity of the developing immune system to induce tolerance to immunizing antigens. This thesis is concerned with the induction of specific immunity in the second trimester ovine fetus using the oral DNA immunization method. In utero oral delivery of naked DNA plasmid was selected as the method of immunization due to previous successes in the third trimester ovine fetus and the immunostimulatory properties of the bacterial DNA backbone, which may help overcome developmental tolerance. Transfection and expression studies in the third trimester ovine fetus revealed the oral mucosal epithelium as the primary site of transgene expression and functionally active antigen was also localized to lymph nodes draining the oral cavity. Efficient transfection and expression of plasmid following oral delivery was specific to the fetus and correlated with a lesser degree of epithelial differentiation. Oral DNA delivery in the second trimester resulted in detection of transgene activity in 100% of treated fetuses and the level of transgene activity was greater than in fetuses treated in the mid-third trimester. Using a plasmid encoding the gene for bovine herpesvirus-1 truncated glycoprotein D (tgD), immunization studies were then conducted in the second trimester fetus. A new lower age limit for fetal immunization was established at 55-60 days gestation (gestation period is 148 days), which coincides with the appearance of lymphocytes in peripheral tissues. Antigen-specific antibody, interferon-× responses and/or neonatal anamnestic responses were detected in 66% of fetuses immunized between 55 and 84 days gestation. The duration of fetal primary immune responses was equivalent to that achieved in young lambs following optimized DNA vaccination, but the magnitude of fetal immune responses was limited. The persistence of immune memory from the second trimester to birth was consistent with experimental data which showed that the duration of immune memory had a stronger correlation to the duration, as compared to the magnitude, of the primary antibody response. Overall, the experiments within showed that oral DNA immunization of the early second trimester fetus is feasible and not associated with the induction of tolerance. These findings suggest that it may be possible to protect against mother-to-child transmission of infectious pathogens by targeting protection at the level of the fetus.

With the combination of computer-assisted image analysis and ultrasonographic imaging technology, it has been possible to study and increase the knowledge in different areas of medicine. Studies of ovarian development in female mammals using ultrasonography have shown a relationship between the day in the estrous cycle and the main structures of the ovary.<p>Ultrasound images of bovine ovaries were used to determine whether ultrasound-detected features can automatically determine the phase in the estrous cycle based on a single day's ultrasound examination of the ovaries. Five ultrasound-detected features of the bovine ovaries were used to determine the phase in the estrous cycle: (1) size of the dominant follicle; (2) size of the first subordinate follicle; (3) size of the second subordinate follicle; (4) size of the corpus luteum and (5) number of subordinate follicles with size ≥ 2mm. The collection of ultrasound images used for this study was formed by a group of 45 pairs of ovaries (left and right) which were imaged on day 3, day = 10 and day ≥ 17 of the estrous cycle corresponding to the metestrus, diestrus and proestrus phases respectively.<p>Four different experiments were performed to test the hypothesis. For experiments 1, 2 and 3 the bovine ovaries were classified into three different classes: day 3 of wave 1 (D3W1), day 1 of wave 2 (D1W2) and day 17 or higher (D≥17) that were related to the follicular development of the ovary and the estrous cycle phases as: metestrus, diestrus and proestrus respectively. For experiment 4 the bovine ovaries were classified into four classes: D3W1, D6W1, D1W2 and D≥17. The additional class (D6W1: day 6 of wave 1) was incorporated to represent the early-diestrus phase in the estrous cycle.<p>Two classifiers were implemented for all experiments and their performances compared: a decision tree classifier and a naive Bayes classifier. The decision tree classifier had the best performance with a classification rate of 100% for experiments 1, 2 and 3, giving a rather simple decision tree which used only two features to make a classification: size of the dominant follicle and size of the corpus luteum, suggesting these are key features in distinguishing between phases in the estrous cycle giving the most relevant information. The naive Bayes had a classification rate of 86.36% for experiment 1, 95.55% for experiment 2 and 90% for experiment 3. The results of this study supported the hypothesis that by using ultrasound detected features of bovine ovaries we can determine automatically the stage in the estrous cycle based on a single day's examination.

Two studies were designed to characterize the effects of a non-steroidal aromatase inhibitor, letrozole, on ovarian function in cattle. The specific objective was to test the hypothesis that letrozole will arrest dominant follicle growth resulting in emergence of a new follicular wave at a predictable interval post-treatment. In a first experiment, postpubertal beef heifers were assigned randomly to four treatment groups and given phosphate-buffered saline (controls; n=10), or letrozole at a dose of 500 (n=9), 250 (n=10), or 125 (n=10) µg/kg intravenously 4 days after follicular ablation (~2.5 days after wave emergence). In a second study, postpubertal beef heifers were assigned randomly to four treatment groups. One group received no treatment (control; n=17) and the other groups (n=9-10) were given 85 µg/kg of letrozole per day (250 µg/kg total dose), from Days 1 to 3, Days 3 to 5, or Days 5 to 7 (Day 0 = pre-treatment ovulation,) corresponding to the periods before, during and after selection of the dominant follicle, respectively. Follicular dynamics were monitored ultrasonically and blood samples were collected for endocrine assays. Follicle diameter profiles and plasma LH, FSH, and estradiol concentrations were analyzed. Additionally, during the second trial, CL diameter profiles and plasma progesterone concentrations were measured. In both studies, the diameter profile of the dominant follicle was larger in heifers treated with letrozole than in control heifers (P<0.05) and the intervals to new wave emergence and onset of regression of the extant dominant follicle were longer (P<0.05) in heifers treated with letrozole than in controls, regardless of the dose (high, medium, or low; single vs multiple) and the stage of the follicle wave in which treatments were initiated. Furthermore, during the second experiment, the mean CL diameter was larger in letrozole-treated heifers, although there were no differences in plasma progesterone concentrations between treated and control animals. The effects on dominant follicle and CL diameter profiles appeared to be the result of the significantly increased plasma LH concentrations observed in letrozole-treated animals during both treatment approaches (single vs multiple dose). Incomplete and inconsistent inhibition of estradiol production and the lack of a surge on FSH observed in both experiments may be a result of insufficient circulating levels of letrozole during the treatment period. In summary, a single or multiple dose of letrozole did not induce regression of the extant dominant follicle, nor did it directly affect FSH release. Conversely, letrozole extended the lifespan of the dominant follicle, in association with increased endogenous levels of LH, thereby delaying the next FSH surge and subsequent follicular wave emergence. Results suggest that letrozole has potential as a non-steroidal method for controlling ovarian function in cattle, but further studies are warranted to clarify dosage and timing of treatment to predictably affect follicular wave dynamics in cattle.

Bovine adenovirus (BAdV)-3 is a non-enveloped, icosahedral virus with a double-stranded DNA genome, and is being developed as a vector for vaccination of animals and humans. Expression of viral genes is divided into early, intermediate, and late phases. The late genes of BAdV-3 are grouped into seven families (L1 to L7) based on usage of common polyadenylation site(s). The L1 region of BAdV-3 encodes the 52K protein, a non-structural protein conserved among members of the family Adenoviridae. In human adenovirus (HAdV)-5, the 52K protein is involved in packaging of the viral DNA into the capsid. The N-terminal half of the protein has been proposed to mediate serotype specificity of DNA packaging. The objective of this study was to characterize the 52K protein of BAdV-3. <p> DNA sequence analysis revealed that the BAdV-3 52K open reading frame encodes a protein of 370 amino acids rather than 331 amino acids as previously reported. Western blotting with anti-52K serum detected the expression of a 40kDa protein at 24 to 72 hrs post-infection. BAdV-3 52K localized predominantly to the nucleus in BAdV-3 infected cells and in transfected cells in the absence of other viral proteins. Analysis of mutant 52K proteins revealed that residues 102-110 were necessary but not sufficient for nuclear import. This suggests that residues upstream or downstream of the identified 52K nuclear localization signal (NLS) are required, or that the function of the NLS is dependent on its conformation within 52K. <p> The nuclear import of 52K is significantly, but not completely, dependent on soluble factors, ATP, and temperature. A peptide competing for binding to importin beta and a peptide encoding the NLS of Ycbp80 were also able to inhibit nuclear import of 52K. However, a dominant negative mutant of Ran was unable to block 52K nuclear import. These results suggest that 52K uses a classical importin alpha/importin beta pathway for nuclear import. In support of this, a specific interaction between 52K and importin alpha-3 was detected. In addition, 52K was able to accumulate in the nucleus in the absence of soluble factors and ATP when the nuclear membrane was permeabilized with detergent. This suggests that, in addition to nuclear import by the importin alpha/importin beta pathway, 52K is able to accumulate in the nucleus by binding to nuclear components. <p> A yeast two-hybrid system identified interactions between BAdV-3 52K and pV, pVI, pVII, and IVa2. However, only the interaction with pVII could be confirmed by GST pulldown. 52K and pVII also interact during BAdV-3 infection. An interaction between 52K and pVII has previously been shown in HAdV-5 infected cells. <p> Mass spectrometry analysis of proteins co-precipitating with BAdV-3 52K identified a cellular protein, NFkB-binding protein (NFBP), which interacted with 52K. The interaction between NFBP and 52K was confirmed <i>in vitro</i> and <i>in vivo</i>. NFBP has been shown to be essential for ribosomal RNA (rRNA) processing. While NFBP is normally localized in the nucleolus, co-expression with 52K results in the redistribution of NFBP from the nucleolus to other parts of the nucleus. While this suggested that redistribution of NFBP by 52K could inhibit rRNA processing during BAdV-3 infection, we were unable to detect a difference in rRNA processing in cells expressing truncated or full-length 52K in the absence of other viral proteins. Since NFBP is a multi-functional protein, future experiments should focus on other possible biological functions of the interaction of NFBP with BAdV-3 52K.

Copper (Cu) is an essential trace element in ruminants such as the cow. Its deficiency leads to a number of debilitating symptoms and can eventually cause death. Secondary Cu deficiency is caused by the presence of chemical antagonists such as the thiomolybdates (TMs) (MoOxS4-x2-; x = 0 3). TMs form in the rumen and then form tightly bound insoluble complexes with Cu. These complexes are then excreted and the Cu is unavailable to the animal. The TMs and their effects on ruminant Cu are the focus of this thesis.<p>This study includes three main bodies of work. First, a method for quantifying the composition of TM mixtures in solution was developed. Second, the rate constants of TM interconversions were determined. Third, reactions between Cu and the TMs were studied. This work is part of an ongoing study in the Reid group to model Cu-ligand speciation in the rumen. <p>Thiomolybdates form by successive replacement of molybdate (MoO42-) O ligands with S. This makes synthesis of the uncontaminated compounds difficult. Mixtures of TMs are best analyzed by UV-visible spectroscopy despite the considerable spectral overlap. The combination of these two issues makes the characterization of the spectra difficult. In this study, a method was developed to establish the spectra of the pure TMs despite cross-contamination. Multivariate curve fitting methods were used to establish the composition of synthesized samples simultaneously with the molar absorptivities of the pure TMs. This was done using a Beers Law model. The composition was determined from a fit using assumed molar absorptivities. The absorptivities were then refined using the composition results. These processes were successively reiterated until both were optimized. The optimized absorptivities could then be used to determine the composition of any TM solution mixture. <p>The kinetics of TM formation under biologically relevant conditions were followed by UV-visible spectroscopy. The spectra were then analyzed, using the method developed above, to determine all TM concentrations. Curve fitting methods were used to simultaneously determine the rate constants of all processes that occurred. Integrated rate equations used in the fitting process were developed using the Laplace Transform method. Rate constants were determined at varying pH, ionic strengths and temperatures. From this information it was shown that TM formation and hydrolysis occurs via an associative mechanism. It was also determined that H2S and not HS- was the sulfide nucleophile in TM formation reactions.<p>This study was then extended to include reactions involving Cu and the TMs. First, the UV-visible spectra of the reaction products of Cu with each TM were characterized. This allowed the kinetics of reactions between Cu and the TMs to be followed. This reaction has been found to proceed via an intermediate. Molar absorptivities for this intermediate were optimized along with the appropriate rate constants. This was done using a combination of mathematical simulations and the curve fitting methods used for the TM kinetics. The resulting rate constants can be compared with those obtained previously in the group using a Cu ion selective electrode. <p>These rate constants were used in conjunction with the TM formation rate constants to perform simulations. The results of these simulations provide a picture of what is expected to occur in the rumen. Reactions were also performed in which TM formation occurred in the presence of Cu. This was then extended to mimic bovine feeding habits. Here, portions of the reactions mixture was removed at various time intervals and replaced with fresh reagents. These experiments were used to gain a qualitative picture of Cu speciation in the presence of the TMs over time. The work presented in this thesis provides a crucial step toward understanding the problem of bovine copper deficiency.