A combination of in situ sampling and numerical modeling was used to investigate the effects of mesoscale (<50 km) circulation patterns and stratification on the evolution of hypoxia on the Louisiana Shelf. Temperature, salinity, and dissolved oxygen concentrations records reveal the presence of an alongshelf meander, which is manifested vertically and horizontally as a wave-like distribution of the properties in the water column. The observations suggest the meander is a ubiquitous characteristic of the shelf with alongshore spatial scale approximately 50 km and less, which is consistent with the locations of sandy shoals along the coast and the local deformation radius. Twelve numerical experiments using an idealized three-dimensional shelf circulation model were performed to evaluate the relative importance of the variable bottom topography and freshwater forcing on the development, evolution, and scales of the dynamic instabilities. The inclusion of the shoals into the bottom topography showed the development of the dynamic instabilities as the flow passed over the shoals and downstream. Introduction of fresh water onto the shelf resulted in greater salinity differences, and, as a consequence in the formation of the dynamically unstable salinity fronts along the plume edge. The combination of the freshwater forcing and shoaling topography produced competing and complex interactions. Six numerical experiments were analyzed in order to investigate the effect of dynamic instabilities on spatial and temporal patterns of dissolved oxygen concentrations along the shelf. Although a linear relationship between Brunt-Väisälä frequency and dissolved oxygen deficit was expected, a nonlinear loop-like relationship was discovered that reflects the response of biochemical properties to the alongshelf variability of the density field. Comparison of the numerical modeling runs to observations of density and dissolved oxygen concentrations on the Louisiana Shelf reinforces the importance of physical processes such as topographic steering and/or freshwater forcing on the alongshore distribution of physical and biochemical properties. It suggests that the time scales of respiration (~3 days) and buoyancy transfer processes (~5-7 days), associated with the physical processes that are responsible for water column stability and ventilation, are similar to the time scales associated with the benthic respiration rates.

Corpus Christi Bay (TX, USA) is a shallow wind-driven bay which is designated as a National Estuary due to its impact on the economy. But this bay experiences periodic hypoxia (dissolved oxygen <2 mg/l) which threatens aerobic aquatic organisms. Development of the Coastal Margin Observation and Assessment System (CMOAS) through integration of real-time observations with numerical modeling helps to understand the processes causing hypoxia in this energetic bay. CMOAS also serves as a template for the implementation of observational systems in other dynamic ecosystems for characterizing and predicting other episodic events such as harmful algal blooms, accidental oil spills, sediment resuspension events, etc. State-of-the-art sensor technologies are involved in real-time monitoring of hydrodynamic, meteorological and water quality parameters in the bay. Three different platform types used for the installation of sensor systems are: 1) Fixed Robotic, 2) Mobile, and 3) Remote. An automated profiler system, installed on the fixed robotic platform, vertically moves a suite of in-situ sensors within the water column for continuous measurements. An Integrated Data Acquisition, Communication and Control system has been configured on our mobile platform (research vessel) for the synchronized measurements and real-time visualization of hydrodynamic and water quality parameters at greater spatial resolution. In addition, a high frequency (HF) radar system has been installed on remote platforms to generate surface current maps for Corpus Christi (CC) Bay and its offshore area. This data is made available to stakeholders in real-time through the development of cyberinfrastructure which includes establishment of communication network, software development, web services, database development, etc. Real-time availability of measured datasets assists in implementing an integrated sampling scheme for our monitoring systems installed at different platforms. With our integrated system, we were able to capture evidence of an hypoxic event in Summer 2007. Data collected from our monitoring systems are used to drive and validate numerical models developed in this study. The analysis of observational datasets and developed 2-D hydrodynamic model output suggests that a depth-integrated model is not able to capture the water current structure of CC Bay. Also, the development of a threedimensional mechanistic dissolved oxygen model and a particle aggregation transport model (PAT) helps to clarify the critical processes causing hypoxia in the bay. The various numerical models and monitoring systems developed in this study can serve as valuable tools for the understanding and prediction of various episodic events dominant in other dynamic ecosystems.

The Gulf of Mexico hypoxic zone is created by strong persistent water stratification and nutrient loading from the Mississippi River which fuels primary production and bacterial decomposition. The Texas-Louisiana shelf becomes seasonally oxygen depleted and hypoxia (O2 less than or equal to 1.4 ml l-1) occurs. Low oxygen environments are conducive for the microbial production of nitrous oxide (N2O), a powerful greenhouse gas found in the atmosphere in trace amounts (319 ppbv). Highly productive coastal areas contribute 61% of the total oceanic N2O production and currently global sources exceed sinks. This study is the first characterization of N2O produced in the Gulf of Mexico hypoxic zone. Because of enhanced microbial activity and oxygen deficiency, it is hypothesized that the Gulf of Mexico hypoxic zone is a source of N2O to the atmosphere. Seasonal measurements of N2O were made during three research cruises in the Northern Gulf of Mexico (Sept. 2007, April 2008, and July 2008). Water column N2O profiles were constructed from stations sampled over time, and bottom and surface samples were collected from several sites in the hypoxic zone. These measurements were used to calculate atmospheric flux of N2O. The Gulf of Mexico hypoxic zone was a source of N2O to the atmosphere, and N2O production was highest during times of seasonal hypoxia. N2O was positively correlated with temperature and salinity, and negatively correlated with oxygen concentration. Atmospheric fluxes ranged from -11.27 to 153.22 umol m-2 d-1. High accumulations of N2O in the water column (up to 2878 % saturated) were associated with remineralization of organic matter at the base of the pycnocline and oxycline. Seasonal hypoxia created a source of N2O to the atmosphere (up to 2.66 x 10-3 Tg N2O for the month of September 2007), but there was a slight sink during April 2008 when hypoxia did not occur. Large fluxes of N2O during the 3 to 5 month hypoxic period may not be counterbalanced by a 7 to 9 month sink period indicating the Gulf of Mexico hypoxic zone may be a net source of N2O to the atmosphere.

This study explored the possibility that upregulation of Hypoxia Inducible Factor-1 (Hif-1)-responsive genes in Human Umbilical Vein Endothelial Cells (HUVEC) would promote and stabilize HUVEC formation into inchoate vascular beds within artificial collagen gels. This experiment was designed to explore the above possibility by sub-cloning Hif-1[alpha], the related chimeric construct Hif-1[alpha]/VP16, and the marker gene dsRed into retroviral expression vectors, producing retroviral vectors containing these genes, and stably transducing HUVEC using these retroviruses. Transduced HUVEC were to be observed in cell culture as well as after implantation into artificial collagen gels that have previously supported vascular bed formation by HUVEC. Our results show, preliminarily, that HUVEC transduced with Hif-1[alpha]/VP16 go into cell-cycle arrest. Attempts to transduce HUVEC with Hif-1[alpha] failed to achieve high enough transduction efficiency to determine the cells angiogenic potential. This study concluded that more experiments need to be conducted to better characterize the effects of hypoxia-responsive gene upregulation in controlling HUVEC angiogenesis and cell-cycle signaling and that straightforward transduction of HUVEC by Hif-1[alpha]/VP16 is probably not sufficient, in itself, to induce in vitro vascular bed formation.

Thesis (M.S.)--Florida State University, 2003. / Advisor: Dr. Nancy Marcus, Florida State University, Dept. of Oceanography. Title and description from dissertation home page (viewed Mar. 2, 2004). Includes bibliographical references.

Increased glucose metabolism may occur in malignant tumours due to altered gene expression or a response to hypoxia. It has been shown that tumours with high levels of glycolysis, indicated by elevated lactate, are less responsive to radiotherapy. It is not clear whether this effect is caused by lactate itself or rather that high lactate is a surrogate for a radioresistant property such as hypoxia. Furthermore, we are not aware of studies that examine the manipulation of lactate production in tumours to alter radiation response. We propose a novel approach of metabolic targeting of HIF-1 to address these issues. HIF-1 is a major regulator of glycolysis and its inhibition would decrease malignant cell metabolism and could lead to a decrease in lactate production. The goal of this pre-clinical study was to evaluate metabolic targeting as a strategy of enhancing radiation response by inhibiting the HIF-1 transcription factor.

Increased glucose metabolism may occur in malignant tumours due to altered gene expression or a response to hypoxia. It has been shown that tumours with high levels of glycolysis, indicated by elevated lactate, are less responsive to radiotherapy. It is not clear whether this effect is caused by lactate itself or rather that high lactate is a surrogate for a radioresistant property such as hypoxia. Furthermore, we are not aware of studies that examine the manipulation of lactate production in tumours to alter radiation response. We propose a novel approach of metabolic targeting of HIF-1 to address these issues. HIF-1 is a major regulator of glycolysis and its inhibition would decrease malignant cell metabolism and could lead to a decrease in lactate production. The goal of this pre-clinical study was to evaluate metabolic targeting as a strategy of enhancing radiation response by inhibiting the HIF-1 transcription factor.

Several research groups have applied elevated hydrostatic pressure to ONH astrocytes cultured on a rigid substrate as an in vitro model for glaucoma. These studies have shown significant biological effects and this hydrostatic pressure model is now becoming generally accepted in the ophthalmic community. However, since the applied pressures were modest the finding of significant biological effects due to pressure alone is surprising. We hypothesized that the application of hydrostatic pressure as described in these studies also altered gas tensions in the culture media. Our goal was to design equipment and carry out experiments to separate the biologic effects of pressure from those of hypoxia on cultured astrocytes. We designed equipment and carried out experiments to subject cultures of DITNC1 astrocytes to the four combinations of two levels of each parameter. We explored the morphology and migration rates of astrocytes, but observed no significant change in any of these properties.

Goldfish subjected to an intermittent short-term aerobic exercise training regime prior to acute hypoxic exposure demonstrated a shift in hypoxia response. Intermittent aerobic training enhanced the aerobic potential of goldfish in the red muscle by increasing maximal activity of citrate synthase by 72% and reduced pyruvate kinase activity by 21% in white muscle. Across red and white muscle tissue, aerobic training caused a decrease in glycogen storage by 19% and 32%, respectively. Liver glycogen stores remained unchanged by training during normoxia. Subsequent hypoxic exposure demonstrated a significant training effect with a77% glycogen depletion in the liver of trained fish compared to a 53% depletion in untrained fish. Hypoxia caused glycogen depletion, glucose mobilization, and ATP depletion in trained and untrained fish muscle tissue. Meanwhile, the liver of trained recovered ATP slower than untrained fish and both liver and plasma had greater lactate accumulation by 1 h hypoxic recovery in trained fish. Alcohol dehydrogenase maximal activity of trained fish responded to hypoxia with a 50% reduction and trained white muscle significantly reduced alcohol dehydrogenase activity during hypoxic recovery. Ethanol was produced with and without training preconditioning in response to hypoxia in red muscle; however, trained fish white muscle showed an ethanol accumulation trend following training and 12 h hypoxia that was significantly cleared during recovery. Ethanol accumulation in white muscle of trained fish may reveal greater perturbation caused by training and hypoxia and/or some developed mechanism for ethanol retention. In effect, this training regime created a very different metabolic profile in goldfish such that during environmental oxygen limitation, trained fish may experience an enhanced metabolic perturbation and greater glycogen depletion which may compromise hypoxic tolerance. / Thesis (Master, Biology) -- Queen's University, 2011-09-30 13:25:36.148

The environment in which animals are maintained is a factor that has the potential to alter the physiologic phenotype. We addressed the hypothesis that the standard animal care (SAC) environment cause significant deviations in the circadian variation of heart rate (HR), body temperature (Tb) and activity (ACT) in chronically instrumented mice. These data were used to inform the design of a subsequent study addressing the hypothesis that loss of transient receptor potential vanilloid 1 (TRPV1) function blunts the thermoregulatory, ventilatory and metabolic responses to hypoxia. Mice were implanted with intraperitoneal transmitters for chronic recording of HR, Tb and ACT. The animal environment study consisted of a 3-week protocol comprised of SAC (wk 1) utilizing standard animal care procedures of a health check and bottle and cage changes SPA (service personnel absent; wk 2) with no SAC interventions and building malfunction (BLDMAL+SAC, wk 3). Mean HR was elevated across the week of SAC, as well as for the light and dark cycles. Cage change caused the most profound changes (lasting 4 h), while health check/bottle change alterations lasted approx. 30 min. TRPV1-/- and TRPV1+/+ (wild-type, WT) mice exposed acutely to hypoxia (FIO2=0.1 for 4 h) resulted in a greater hypometabolic response for the mutant compared with WT genotype, reaching a lower value for HR, Tb, ACT, V ̇CO2 (carbon dioxide production) and ventilation. We conclude that the animal care environment provides a novel environment to assess murine phenotype and must be considered in genotype/phenotype assessments. Further, TRPV1 provides a significant tonic input to the integrated thermoregulatory, metabolic and ventilatory responses to hypoxia. / Thesis (Master, Physiology) -- Queen's University, 2012-08-27 17:51:48.022