Life Sciences Commons^™

Genetic Basis Of Thermal Divergence In Saccharomyces Species, Xueying C. Li

Arts & Sciences Electronic Theses and Dissertations

The genetic architecture of phenotypic divergence is a central question in evolutionary biology. Genetic architecture is impacted by whether evolution occurs through accumulation of many small-effect or a few large-effect changes, the relative contribution of coding and cis-regulatory changes, and the prevalence of epistatic effects. Our empirical understanding of the genetic basis of evolutionary change remains incomplete, largely because reproductive barriers limit genetic analysis to those phenotypes that distinguish closely related species. In this dissertation, I use hybrid genetic analysis to examine the basis of thermal divergence between two post-zygotically isolated species, Saccharomyces cerevisiae and S. uvarum. S. cerevisiae is …

Mechanisms Of S1p-Induced Endothelial Barrier Enhancement, Natascha Guimarães Alves

USF Tampa Graduate Theses and Dissertations

Excessive microvascular permeability is a serious complication involved in traumatic injury and inflammatory diseases. Alcohol intoxication can exacerbate the physiological derangements produced by microvascular endothelial barrier dysfunction in such disease conditions. Sphingosine-1-phosphate (S1P) has known endothelial barrier-protective properties, and has been shown to ameliorate microvascular leakage in a model of combined alcohol intoxication and hemorrhagic shock and resuscitation (HSR). However, whether the barrier-protective properties of S1P extend to endothelial cells of the blood-brain barrier (BBB) is unclear. The mechanisms of S1P-induced barrier protection during alcohol intoxication or HSR are also unknown. In the current study, we tested the hypothesis that …

Importance Of S. Cerevisiae Rcf1 And Rcf2 Proteins For The Mitochondrial Protonmotive Force Generation, Vera Strogolova

Dissertations (1934 -)

Mitochondria are the site of oxidative phosphorylation (OXPHOS) pathway, which can supply majority of energy in a eukaryotic cell. OXPHOS enzyme activities generate electrochemical gradient known as mitochondrial protonmotive force (PMF). PMF coordinates OXPHOS enzyme activities and supports essential cell survival functions such as transport of proteins and metabolites in and out of mitochondria. PMF is maintained despite variations in cellular energy demand and oxygen availability.Mitochondrial proteins belonging to the conserved hypoxia induced gene domain (HIGD) family improve cell survival during the hypoxic and hypoglycemic stress. Their molecular function is not fully understood but they seem to act through …

Functional And Skeletal Muscle Impairments In Progressive Diabetic Ckd, Daniel Bittel

Arts & Sciences Electronic Theses and Dissertations

1-in-3 persons with type 2 diabetes (T2DM) develop chronic kidney disease (CKD), which is characterized by progressive renal dysfunction leading to end-stage renal disease. In response to elevated blood glucose and systemic inflammation of diabetes, a process of active thickening of the renal glomerular basement membrane ensues with concomitant damage to the structural supports (podocytes) of the kidneyճ filtration barrier. This results in impaired renal filtration. The metabolic sequelea of T2DM and CKD also, synergistically, alter skeletal muscleճ degradative pathways, satellite cell function (muscle reparative cells), and mitochondrial health (muscle energetic machinery) -- resulting in muscle breakdown, poor muscle quality, …

Exercise Preconditioning And Tfam Overexpression Diminish Skeletal Muscle Atrophy., Nicholas Todd Theilen

Electronic Theses and Dissertations

This dissertation is an analysis of skeletal muscle atrophy and a molecular assessment of potential preventative treatments. Chapter I begins with a background of skeletal muscle atrophy along with an analysis of associated molecular pathways. Here, we discuss how skeletal muscle atrophy is the consequence of protein degradation exceeding protein synthesis and can occur when a muscle is abnormally disused. The development of therapies prior to skeletal muscle atrophy settings to diminish protein degradation is scarce and could be useful to prevent negative clinical outcomes of patients who must unload and disuse musculature over extended periods. Mitochondrial dysfunction is associated …

Mitochondrial Mrna Translation Is Required For Maintenance Of Oxidative Capacity, David Lee

Graduate Theses and Dissertations

Oxidative metabolism is required to produce adequate energy to sustain human life. A primary example of deteriorating oxidative capacity is seen in the cardiac musculature during chronic heart failure. This suggests that by improving oxidative potential, chronic heart disease could be mitigated and one approach to accomplish this may be through targeting the mt-mRNA translation system. Purpose: This investigation’s purpose was to characterize disruptions in mt-mRNA translation machinery in multiple forms of cardiomyopathy and to determine if mitochondrial mRNA translation initiation factor (mtIF2) is necessary to maintain oxidative capacity in cardiomyocytes. Methods Using a combination of animal and cell culture …

Insights Into The Cellular Trafficking Of Perilipin 5, Hannah M. Bailey

Undergraduate Honors Thesis Projects

Perilipins are a family of five proteins found on the surface of lipid storage droplets in nearly all tissues. These proteins act as cofactors for lipases and scaffolding for other proteins involved in lipid metabolism. In addition to the lipid droplet surface, members of the perilipin family have been found in the cytosol, endoplasmic reticulum, plasma membrane and mitochondria. The localization of these proteins is in part due to the phosphorylation state of the perilipin in question. Many other biological processes occur through kinase pathways, which have numerous cellular outcomes. Recently, perilipin 5 has been shown to localize to the …

Hydraulic Fracturing Fluid Biocide, Tributyl Tetradecyl Phosphonium Chloride, Causes Mitochondrial Dysfunction That Is Enhanced By Sodium Chloride In Chironomus Riparius, Zainab Hussain Alali

Seton Hall University Dissertations and Theses (ETDs)

Tributyl tetradecyl phosphonium chloride (TTPC) is a biocide utilized in the hydraulic fracturing process to extract oil and natural gas from deep underground. This study used 4^th instar Chironomus riparius to investigate the toxicity of TTPC, NaCl, and TTPC+NaCl. Our results show that the 24 h LC₅₀s for TTPC, NaCl, and TTPC+NaCl were 0.57 mg/L, >10,000 mg/L, and 0.32 mg/L, respectively, while the 48 h LC₅₀s for the same treatments were 0.48 mg/L, 9808 mg/L, and 0.22 mg/L, respectively. Additionally, TTPC’s mechanism of action was investigated by measuring the levels of adenosine triphosphate (ATP), superoxide …

Modulation Of Electron Transport By Metformin In Cardiac Protection: Role Of Complex I, Ahmed Abdul Hussein Mohsin

Theses and Dissertations

Modulation of mitochondrial complex I during reperfusion reduces cardiac injury. Complex I exists in two structural states: active (A) and deactive (D) with transition from A→D during ischemia. Reperfusion reactivates D→A with an increase in ROS production. Metformin preserves the D-Form. Our aim was to study the contribution of maintenance of deactivation of complex I during early reperfusion by metformin to protect against ischemia reperfusion injury. Our results showed that metformin decreased H9c2 cardiomyoblast apoptosis and total cell death following simulated ischemia for six hours followed by reoxygenation for twenty four hours compared to untreated cells. Reactive oxygen species (ROS) …

Functional Variation In The Mitochondrial Genome Of The Yeast Saccharomyces Cerevisiae, John F. Wolters

Graduate Dissertations and Theses

Mitochondrial haplotypes contribute to functional diversity in natural populations. Uniparental inheritance makes it difficult to characterize the genetic architecture of mitochondrially driven phenotypes. In this work I explored the natural diversity of mitochondrial genomes in the yeast Saccharomyces cerevisiae. Few complete mitochondrial genomes were available for S. cerevisiae owing to challenges in high-throughput sequencing. I developed sequencing strategies using new technologies to generate complete high quality yeast mitochondrial genomes. Comparisons of 100 complete yeast mitochondrial genomes demonstrated extensive variation between populations in coding sequences and variable introns.

I demonstrated that these mitochondrial variants directly caused growth differences in strains with …

Studies On E2 Conjugation Enzyme Partners Of Mulan E3 Ubiquitin Ligase, Rebekah J. Fitzpatrick

Honors Undergraduate Theses

Mulan is an E3 ubiquitin ligase embedded in the outer mitochondria membrane. Mulan’s participation in the ubiquitination process is conducted through its cytosol exposed RING finger domain, and its ability to modulate protein ubiquitination makes it a key player in mitochondrial and cellular homeostasis. Mulan is known to be involved in mitochondrial fission, fusion, mitochondrial stress, apoptosis, and Parkin-independent mitophagy. Dysregulation of Mulan in mice has been shown to correlate with human neurodegenerative disorders and heart disease. Accumulation of Mulan is predicted to be responsible for the motor neuron degeneration 2 (mnd2) phenotype in mutant mice through the deregulation of …