Life Sciences Commons^™

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

Dissertations & Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand ^[1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …

Impact Of Sleep And Circadian Disruption On Energy Balance And Diabetes: A Summary Of Workshop Discussions, Deanna M. Arble, Joseph Bass, Cecilia Diniz Behn, Matthew P. Butler, Etienne Challet, Charles Czeisler, Christopher M. Depner, Joel Elmquist, Paul Franken, Michael A. Grandner, Erin C. Hanlon, Alex C. Keene, Michael J. Joyner, Ilia Karatsoreos, Philip A. Kern, Samuel Klein, Christopher J. Morris, Allan I. Pack, Satchidananda Panda, Louis J. Ptacek, Naresh M. Punjabi, Paolo Sessone-Corsi, Frank A. Scheer, Richa Saxena, Elizabeth R. Seaquest, Matthew S. Thimgan, Eve Van Cauter, Kenneth P. Wright

Biological Sciences Faculty Research and Publications

A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact …

Tradeoffs Of Warm Adaptation In Aquatic Ectotherms: Live Fast, Die Young?, A. P. Porreca, E. Martinez, R. E. Colombo, Michael A. Menze

Michael Menze

In the face of a changing climate, questions regarding sub-lethal effects of elevated habitat temperature on the physiology of ectotherms remain unanswered. In particular, long-term responses of ectotherms to the warming trend in tropical regions are unknown and significantly understudied due primarily to the difficulties in specimen and community traceability. In freshwater lakes employed as cooling reservoirs for power plants, increased physiological stress from high water temperature can lead to an increase in mortality, reduce growth, and potentially alter the community structure of fishes. Throughout this study, we employ this highly tractable system to assess how elevated thermal regimes can …

Tradeoffs Of Warm Adaptation In Aquatic Ectotherms: Live Fast, Die Young?, A. P. Porreca, E. Martinez, R. E. Colombo, Michael A. Menze

Faculty Research & Creative Activity

In the face of a changing climate, questions regarding sub-lethal effects of elevated habitat temperature on the physiology of ectotherms remain unanswered. In particular, long-term responses of ectotherms to the warming trend in tropical regions are unknown and significantly understudied due primarily to the difficulties in specimen and community traceability. In freshwater lakes employed as cooling reservoirs for power plants, increased physiological stress from high water temperature can lead to an increase in mortality, reduce growth, and potentially alter the community structure of fishes. Throughout this study, we employ this highly tractable system to assess how elevated thermal regimes can …

Tradeoffs Of Warm Adaptation In Aquatic Ectotherms : Live Fast, Die Young?, A. Porreca, E. Martinez, R. Colombo, Michael Menze

Faculty Scholarship

In the face of a changing climate, questions regarding sub-lethal effects of elevated habitat temperature on the physiology of ectotherms remain unanswered. In particular, long-term responses of ectotherms to the warming trend in tropical regions are unknown and significantly understudied due primarily to the difficulties in specimen and community traceability. In freshwater lakes employed as cooling reservoirs for power plants, increased physiological stress from high water temperature can lead to an increase in mortality, reduce growth, and potentially alter the community structure of fishes. Throughout this study, we employ this highly tractable system to assess how elevated thermal regimes can …

Polyq-Dependent Rna–Protein Assemblies Control Symmetry Breaking, Changhwan Lee, Patricia Occhipinti, Amy S. Gladfelter

Dartmouth Scholarship

Dendritic growth in fungi and neurons requires that multiple axes of polarity are established and maintained within the same cytoplasm. We have discovered that transcripts encoding key polarity factors including a formin, Bni1, and a polarisome scaffold, Spa2, are nonrandomly clustered in the cytosol to initiate and maintain sites of polarized growth in the fungus Ashbya gossypii. This asymmetric distribution requires the mRNAs to interact with a polyQ-containing protein, Whi3, and a Pumilio protein with a low-complexity sequence, Puf2. Cells lacking Whi3 or Puf2 had severe defects in establishing new sites of polarity and failed to localize Bni1 protein. Interaction …

Saponin-Permeabilization Is Not A Viable Alternative To Isolated Mitochondria For Assessing Oxidative Metabolism In Hibernation, James Staples, Katherine E. Mathers

Biology Publications

Saponin permeabilization of tissue slices is increasingly popular for characterizing mitochondrial function largely because it is fast, easy, requires little tissue and leaves much of the cell intact. This technique is well described for mammalian muscle and brain, but not for liver. We sought to evaluate how saponin permeabilization reflects aspects of liver energy metabolism typically assessed in isolated mitochondria. We studied the ground squirrel (Ictidomys tridecemlineatus Mitchell), a hibernating mammal that shows profound and acute whole-animal metabolic suppression in the transition from winter euthermia to torpor. This reversible metabolic suppression is also reflected in the metabolism of isolated …

Saponin-Permeabilization Is Not A Viable Alternative To Isolated Mitochondria For Assessing Oxidative Metabolism In Hibernation, Katherine E. Mathers, James F. Staples

Biology Publications

Saponin permeabilization of tissue slices is increasingly popular for characterizing mitochondrial function largely because it is fast, easy, requires little tissue and leaves much of the cell intact. This technique is well described for mammalian muscle and brain, but not for liver. We sought to evaluate how saponin permeabilization reflects aspects of liver energy metabolism typically assessed in isolated mitochondria. We studied the ground squirrel (Ictidomys tridecemlineatus Mitchell), a hibernating mammal that shows profound and acute whole-animal metabolic suppression in the transition from winter euthermia to torpor. This reversible metabolic suppression is also reflected in the metabolism of isolated liver …

Cytoskeletal Dynamics: A View From The Membrane, Magdalena Bezanilla, Amy S. Gladfelter, David R. Kovar, Wei-Lih Lee

Dartmouth Scholarship

Many aspects of cytoskeletal assembly and dynamics can be recapitulated in vitro; yet, how the cytoskeleton integrates signals in vivo across cellular membranes is far less understood. Recent work has demonstrated that the membrane alone, or through membrane-associated proteins, can effect dynamic changes to the cytoskeleton, thereby impacting cell physiology. Having identified mechanistic links between membranes and the actin, microtubule, and septin cytoskeletons, these studies highlight the membrane’s central role in coordinating these cytoskeletal systems to carry out essential processes, such as endocytosis, spindle positioning, and cellular compartmentalization.

Metabolic Effects Of Bariatric Surgery In Mouse Models Of Circadian Disruption, Deanna M. Arble, Darleen A. Sandoval, Fred W. Turek, Stephen C. Woods, Randy J. Seeley

Biological Sciences Faculty Research and Publications

Background/Objectives:

Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (for example, night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared with the non-disrupted population. However, it is unclear whether the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity.

Subjects/Methods:

Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in mouse models of genetic and environmental circadian disruption.

Results:

VSG led to a reduction in body weight and fat mass in …

The Effects Of Suspended Sediment On Japanese Medaka (Oryzias Latipes) And Mosquitofish (Gambusia Affinis) Metabolism, Brandy L. Bossle, Ruben R. Goforth, Shem D. Unger, Olin E. Rhodes Jr.

Journal of the South Carolina Academy of Science

Sedimentation is recognized as a significant environmental stressor in aquatic ecosystems and high amounts of suspended sediments (SS) in streams are known to negatively affect aquatic organisms. In particular, it has been hypothesized that many fish species mayexhibit increased respiration rates when exposed to elevated SS. To evaluate this hypothesis, we evaluated the acute response (3 hour exposure) of two small, freshwater fish species exposed to high suspended sediment loads using experimental respirometry chambers which measure oxygen consumption as a proxy of metabolism. Our results indicate that Japanese Medaka (Oryzias latipes) did not exhibit a significantly greater oxygen …

Mechanisms Underlying Weight Loss And Metabolic Improvements In Rodent Models Of Bariatric Surgery, Deanna M. Arble, Darleen A. Sandoval, Randy J. Seeley

Biological Sciences Faculty Research and Publications

Obesity is a growing health risk with few successful treatment options and fewer still that target both obesity and obesity-associated comorbidities. Despite ongoing scientific efforts, the most effective treatment option to date was not developed from basic research but by surgeons observing outcomes in the clinic. Bariatric surgery is the most successful treatment for significant weight loss, resolution of type 2 diabetes and the prevention of future weight gain. Recent work with animal models has shed considerable light on the molecular underpinnings of the potent effects of these ‘metabolic’ surgical procedures. Here we review data from animal models and how …

Changes In Gene Expression In Sirt3 Knockout Liver Cells, Randa Tao, Jamie Leclerc, Kübra Yildiz, Seong-Hoon Park, Barbara Jung, David Gius, Özkan Özden

Turkish Journal of Biology

The sirtuin (SIRT) gene family is reported to regulate critical intracellular processes from aging to cellular metabolism and repair. SIRT3 knockout (SIRT3-/-) mice develop receptor positive mammary tumors starting at 13 months and SIRT3 expression is decreased in human breast cancer samples as well as several other diseases. It is established that carcinogenesis results from the accumulation of multiple aberrant genetic events including the activation of oncogenes and inactivation of tumor-suppressor genes. To determine the potential early genomic events that may play a role in the tumor-permissive phenotype observed in SIRT3-/- cells, we compared gene expression profile in SIRT3-/- and …

Tradeoffs Of Warm Adaptation In Aquatic Ectotherms: Live Fast, Die Young?, Eloy Martinez, Anthony Porreca, Robert Colombo, Michael Menze

Faculty Research & Creative Activity

In the face of a changing climate, questions regarding sub-lethal effects of elevated habitat temperature on the physiology of ectotherms remain unanswered. In particular, long-term responses of ectotherms to the warming trend in tropical regions are unknown, and understudied due to the difficulties in specimen and community traceability. In freshwater lakes employed as cooling reservoirs for power plants, increased physiological stress from high water temperature can potentially alter the community structure of fishes. We employ this highly tractable system to assess how thermal regimes can alter the physiology and ecology of aquatic species. We documented a significantly reduced lifespan, growth …

Tradeoffs Of Warm Adaptation In Aquatic Ectotherms: Live Fast, Die Young?, Eloy Martinez, Anthony P. Porreca, Robert E. Colombo, Michael A. Menze

Eloy Martinez

In the face of a changing climate, questions regarding sub-lethal effects of elevated habitat temperature on the physiology of ectotherms remain unanswered. In particular, long-term responses of ectotherms to the warming trend in tropical regions are unknown, and understudied due to the difficulties in specimen and community traceability. In freshwater lakes employed as cooling reservoirs for power plants, increased physiological stress from high water temperature can potentially alter the community structure of fishes. We employ this highly tractable system to assess how thermal regimes can alter the physiology and ecology of aquatic species. We documented a significantly reduced lifespan, growth …