The Francolins constitute the largest genus in the Galliform family Phasianidae. There is little accord concerning the taxonomic classification of its members. In the past, information on this group has been provided by morphological and palaeontological evidence. An investigation into the molecular history of this group is presented, using mitochondrial DNA (mtDNA) as an evolutionary tool. A comparison of mtDNA restriction fragment lengths has been used to help define the phylogenetic relationships between 13 southern African Francolin species and a selected outgroup, the Japanese Quail. Both cladistic and distance-based analytical methods have been used to construct phylogenies from the molecular fragment data. The trees relating the Francolins are in general agreement with the traditional classification based on morphological, behavioural and morphometric studies, but differ in the branching order of two species, F. levaillantii and F. hartlaubi. A recent proposal for the partitioning of the genus into two monophyletic assemblages of quail-like "partridges" and pheasant-like "francolins" is supported by mtDNA fragment data, with the exception of the two aberrant taxa. On the basis of the initial fragment size comparison, F. hartlaubi and F. levaillantii constitute part of an unresolved quadrichotomy at the base of the tree. A restriction endonuclease site mapping approach has been utilized to provide a deeper resolution for the molecular phylogeny. Detailed mtDNA restriction endonuclease maps of F. levaillantii, F. hartlaubi, two species representing the "partridge" and "francolin" monophyletic groups respectively, and also of the Madagascar Partridge, have been constructed. Phylogenetic analysis of this data has helped to resolve the problematic placement of the two aberrant taxa by showing an early separation of F. levaillantii from the "partridge" lineage, and of F. hartlaubi from the "francolin" lineage. The Madagascar Partridge was anticipated to be a likely sister-taxon to the whole group, but instead appears to have close relationships within the "partridge" lineage.

Mutations affecting the mitochondrial electron transport chain cause numerous neurodegenerative disorders in humans and affect longevity in other organisms. A natural model system to study the relationship between mitochondrial function and aging within an evolutionary or population genetic context has been lacking. Natural populations of Caenorhabditis briggsae nematodes were recently found to harbor mitochondrial genetic variation with likely functional consequences for aging. Specifically, C. briggsae isolates containing high frequencies of a deletion mutation affecting the mitochondrial NADH dehydrogenase 5 (ND5) gene were found to have reduced reproductive fitness and lifespan and elevated levels of mutagenic superoxide. Here, rates of growth and aging and aerobic respiratory capacity were evaluated in several isolates spanning the range of mitochondrial genetic variation in this species. There is considerable variation among isolates for all measured traits, although the observed relationships between isolate-specific trait means and ND5 deletion frequency did not always conform to my expectations. In an effort to determine whether the among-isolate phenotypic variation is due to mitochondrial rather than to nuclear genetic variation, inter-population hybrids of C. briggsae were created and compared to the progenitor isolates. Surprisingly, evidence for paternal mitochondrial inheritance was detected in many of these hybrid lines. Where mitochondrial genomes were maternally inherited as expected, intergenomic epistasis appears to contribute to fitness, longevity, and aging in this species.

No description available.

No description available.

<P> The study of apoptosis is a rapidly growing field due to its relevance not only to development, but also its relationship to several diseases such as cancer. The Bcl-2 family of proteins function at the mitochondrial membrane, where many apoptotic stimuli converge. There are three main theories on the regulation of the Bcl-2 family proteins, supported by several methods of in vitro and cell-based studies. </p> <p> Mitochondria isolated from wild type and Bak-/-C57BL6 mouse liver are free of Bax, Bci-XL and Bid as determined by immunoblotting. A comparison of the two membranes and the use of recombinant proteins demonstrated that tBid activated Bak or Bax to permeabilize the membrane in this system, and lower concentrations of tBid were required for membrane permeabilization in the presence of both Bak and Bax. Recombinant Bci-XL inhibited this process, indicated by a decrease in cytochrome c release. Mutant recombinant proteins demonstrated that Bci-XL inhibits cytochrome c release through interactions with Bax/Bak and tBid, and by a third protein-independent mechanism. Together, this supports the Embedded Together Model. </p> <p> The mitochondrial system also functions as an intermediate in the study of inhibitors of the Bcl-2 family of proteins. Potential inhibitors 3e and 3e-D2 previously demonstrated to bind Bci-XL through fluorescence polarization were shown to have a Bcl-2 protein-independent method of membrane permeabilization that has not yet been determined. 3e also functioned as an activator of Bax and Bak. Similar to fluorescence polarization experiments, the dimeric compound 3e-D2 was more potent than monomeric 3e. </p> <p> A comparison of membranes in the presence and absence of Bak provides a robust system in which to study multiple facets of apoptosis, including but not limited to regulation of Bcl-2 proteins and the development of proteinspecific inhibitors. </p> / Thesis / Master of Science (MSc)

Mitochondrial diseases are a group of heterogenous disorders that share common cellular consequences resulting from mitochondrial dysfunction: (i) decreased ATP production; (ii) increased reliance on alternative anaerobic energy sources; and (iii) increased production of reactive oxygen species. Objective: We evaluated the effect of a combination (COMB) therapy comprising creatine monohydrate, coenzyme Q1 and lipoic acid to target the above mentioned consequences using a randomized, double-blind, placebo-controlled, crossover study design in patients with mitochondrial cytopathies. Results: Compared with placebo, the COMB therapy resulted in lower resting plasma lactate concentrations, lower urinary 8-isoprostane excretion and attenuated the decline of peak dorsiflexion strength in all patient groups. Improved body composition was only observed in patients in the MELAS group. Interpretation: These results suggest that combination therapies targeting multiple final common pathways of mitochondrial dysfunction favorably influence surrogate markers of cellular energy dysfunction. Future therapies should be designed to target specific mitochondrial diseases to provide the greatest therapeutic benefits for those patients. In addition, future studies employing larger sample sizes in homogeneous groups of patients will be required to determine whether such combination therapies will influence function and quality of life. / Thesis / Master of Science (MS)

With the aging of the baby boom population and an increased life expectancy, individuals aged 65 years and older are the fastest growing segment of our population. Aging brings about changes in skeletal muscle such as reduced muscle strength and mass, as well as cellular deficits such as increased production of reactive oxygen species (ROS), and mitochondrial DNA (MtDNA) deletions and mutations. Muscle mass declines at a rate of 1-2% each year after the age of 50, leading to muscle weakness, functional impairments, loss of independence, and an increase in falls. Additional declines in muscle mass and reduced muscle strength may result in a lower resting metabolic rate, reduced lipid oxidative capacity, increased adiposity, and insulin resistance. The rising number of individuals aged 65+ will increase demands on health care and health care costs, possibly leading to inadequate public resources and less care for the aged. This large societal impact, coupled with the aging of our population, suggests a clear need for methods that will improve the aging phenotype to enhance functionality, quality of life, and overall health for our aging population. This investigation aspires to delve into a relatively unexplored area of aging research and evaluate potential means that could help improve the aging phenotype. The associated mitochondrial impairments, mitochondrial mediated apoptosis, and mitochondrial DNA (MtDNA) deletions and mutations that accompany aging lead to a decline in physical fitness and oxidative capacity, and exercise has been shown to reverse or help prevent many of these disturbances. Resistance exercise training (RT) is currently the most effective known strategy to stimulate skeletal muscle hypertrophy and increase strength. Strength gains after RT lead to an improvement in activities of daily living and quality of life. There is some evidence suggesting that RT may lead to increased antioxidant enzyme capacity, decreased ROS production and increased electron transport chain (ETC) function in older individuals. The present study will lay a foundation for future research and further developments in the area of RT, mitochondrial function and aging. / Ph. D.

No / We have assessed the histological preservation of naturally degraded human hair shafts, and then assayed each for levels of amplifiable mitochondrial DNA and damage-associated DNA miscoding lesions. The results indicate that as sample histology is altered (i.e. as hairs degrade) levels of amplifiable mitochondrial DNA decrease, but no correlation is seen between histology and absolute levels of mitochondrial DNA miscoding lesions. Nevertheless, amplifiable mitochondrial DNA could be recovered across the complete range of the histological preservation spectrum. However, when template copy number is taken into consideration, a correlation of miscoding lesions with histology is again apparent. These relationships indicate that a potential route for the generation of misleading mitochondrial sequence data exists in samples of poor histology. Therefore, we argue that in the absence of molecular cloning, the histological screening of hair may be necessary in order to confirm the reliability of mitochondrial DNA sequences amplified from hair, and thus represents a useful tool in forensic mitochondrial DNA analyses.

Le génome mitochondrial montre une grande variabilité de taille et de contenu génique chez les plantes vertes. Près d'une dizaine de génomes mitochondriaux de chlorophytes ont été complètement séquences, incluant le génome de la trebouxiophyte Prototheca wickerhamii. Cette algue est la seule trebouxiophyte qui a été examinée jusqu'à maintenant; puisqu'elle est non-photosynthétique, l'architecture de son génome mitochondrial pourrait ne pas être représentative de la classe Trebouxiophyceae. C'est pour ces raisons que nous avons entrepris le séquençage du génome mitochondrial de Leptosira terrestris, une autre trebouxiophyte. Ce génome, dont la séquence a été déterminée par la méthode shotgun, possède une taille de 111124 pb. Il contient 57 gènes, dont 27 codant pour des ARN de transfert. Dix-huit introns ont été trouvés, faisant de Leptosira l'algue qui possède le plus d'introns au niveau de son génome mitochondrial. Les données phylogénétiques recueillies placent Leptosira comme un intermédiaire chez les trebouxiophytes.

No description available.