2020 Abstracts
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Proteomic Analysis of Trichopteran Silk Fibre
Frandsen, Paul; Bursell, Madeline; Taylor, Adam; Wilson, Seth; Steeneck, Amy; Stewart, Russell (Brigham Young University)
Faculty Advisor: Frandsen, Paul (Life Sciences, Plant and Wildlife Sciences)
Caddisfly (Insecta: Trichoptera) silk is unique from other insect's silk in that it retains its adhesive capabilities, strength and viscoelasticity when submerged in water. To understand how caddisfly silk is capable of possessing these characteristics, it is essential to understand the protein foundation of the silk proteins. Caddisfly silk is complex and made up of different structures generated by processes that are unique to caddisfly silk. H-Fibroin and L-Fibroin have been identified as two of the major protein components within caddisfly silk (Hatano & Nagashima, 2015). The caddisfly silk fibre experiences unique structures not typically seen in nature. An understanding of the primary structure of the silk fibre is essential in understanding the complexity of the silk's capabilities. In this study, we used proteomic techniques to analyze the complex H-Fibroin protein and the silk fibre in order to look at the underlying structural features of the protein. In doing so, we identified post-translational phosphorylation, metal cation incorporation, and other structural features which contributes to Caddisfly silk's adhesive capabilities, strength and viscoelasticity when submerged in water.
Faculty Advisor: Frandsen, Paul (Life Sciences, Plant and Wildlife Sciences)
Caddisfly (Insecta: Trichoptera) silk is unique from other insect's silk in that it retains its adhesive capabilities, strength and viscoelasticity when submerged in water. To understand how caddisfly silk is capable of possessing these characteristics, it is essential to understand the protein foundation of the silk proteins. Caddisfly silk is complex and made up of different structures generated by processes that are unique to caddisfly silk. H-Fibroin and L-Fibroin have been identified as two of the major protein components within caddisfly silk (Hatano & Nagashima, 2015). The caddisfly silk fibre experiences unique structures not typically seen in nature. An understanding of the primary structure of the silk fibre is essential in understanding the complexity of the silk's capabilities. In this study, we used proteomic techniques to analyze the complex H-Fibroin protein and the silk fibre in order to look at the underlying structural features of the protein. In doing so, we identified post-translational phosphorylation, metal cation incorporation, and other structural features which contributes to Caddisfly silk's adhesive capabilities, strength and viscoelasticity when submerged in water.
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Methylmercury exposure in orb weaver spiders (Neoscona oaxacensis) on Antelope Island State Park
Faulkner, Megan; Stoneham, Lisa; Brasso, Rebecka (Weber State University)
Faculty Advisor: Brasso, Rebecka (College of Science, Zoology)
Mercury is a toxic heavy metal that poses significant health risks to humans and wildlife. The organic form of mercury, methylmercury (MeHg), is converted from its inorganic form via microbial methylation primarily in aquatic systems. Methylmercury is dangerous because it attaches to proteins in blood and muscle and biomagnifies in food webs. The goal of this project, is to determine mercury concentrations in western spotted orb weaver spiders (Neoscona oaxacensis) collected from two sites on Antelope Island State Park. Previous studies have shown orb weavers associated with the Great Salt Lake ecosystem to accumulate significant methylmercury, connecting the aquatic and terrestrial ecosystems through a shared food web. The Great Salt Lake surrounding Antelope Island has historically shown some of the highest levels of Hg in surface waters in the United States and has both an abundance of orb weaver spiders and their preferred prey—brine flies. We tested the hypothesis that mercury concentrations in orb weaver spiders would differ between two sites on the island based on differences in environmental conditions (salinity) in the water where brine flies develop. All spiders were sexed, weighed, and individually analyzed for total mercury concentration using a Nippon MA-3000 Direct Mercury Analyzer.
Faculty Advisor: Brasso, Rebecka (College of Science, Zoology)
Mercury is a toxic heavy metal that poses significant health risks to humans and wildlife. The organic form of mercury, methylmercury (MeHg), is converted from its inorganic form via microbial methylation primarily in aquatic systems. Methylmercury is dangerous because it attaches to proteins in blood and muscle and biomagnifies in food webs. The goal of this project, is to determine mercury concentrations in western spotted orb weaver spiders (Neoscona oaxacensis) collected from two sites on Antelope Island State Park. Previous studies have shown orb weavers associated with the Great Salt Lake ecosystem to accumulate significant methylmercury, connecting the aquatic and terrestrial ecosystems through a shared food web. The Great Salt Lake surrounding Antelope Island has historically shown some of the highest levels of Hg in surface waters in the United States and has both an abundance of orb weaver spiders and their preferred prey—brine flies. We tested the hypothesis that mercury concentrations in orb weaver spiders would differ between two sites on the island based on differences in environmental conditions (salinity) in the water where brine flies develop. All spiders were sexed, weighed, and individually analyzed for total mercury concentration using a Nippon MA-3000 Direct Mercury Analyzer.
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On the Relationship of Diabetes and Sleep Apnea: Evolution and Epigenetics
Wilson, Nancy; Johnson, Steven (Brigham Young University)
Faculty Advisor: Johnson, Steven (Life Sciences, Microbiology & Molecular Biology)
Diabetes is the seventh leading cause of death in the United States today. Between sixty and ninety percent of diabetics also have sleep apnea. Although both sleep apnea and diabetes engender weight gain, the comorbidity of the two conditions is higher than can be explained by obesity alone.
In this study we explore the advantages of and evidence for the coevolution of diabetes and sleep apnea.
There is a metabolic shift that takes place when the cells of the heart need repair. Normally, hypoxic events cause a shift in heart-cell metabolism toward a high-glucose energy use. This shift mechanism is still fully functional in a diabetic heart cell, but because the underlying diabetes shifts the cellular metabolism to a primarily fatty-acid-based energy use, even a normally functioning hypoxia-induced cascade does not lead to full glucose metabolism or normal cellular repair.
So sleep apnea might serve a useful function in instigating heart tissue repair in cells. This suggests that sleep apnea and diabetes are not just frequently found together, but one condition may be causing the other.
After discussing some of the possible evolutionary drivers for co-adaptation of sleep apnea and diabetes, we examine some of the epigenetic marks associated with the two conditions, laying the groundwork for a better understanding of the underlying etiology.
Faculty Advisor: Johnson, Steven (Life Sciences, Microbiology & Molecular Biology)
Diabetes is the seventh leading cause of death in the United States today. Between sixty and ninety percent of diabetics also have sleep apnea. Although both sleep apnea and diabetes engender weight gain, the comorbidity of the two conditions is higher than can be explained by obesity alone.
In this study we explore the advantages of and evidence for the coevolution of diabetes and sleep apnea.
There is a metabolic shift that takes place when the cells of the heart need repair. Normally, hypoxic events cause a shift in heart-cell metabolism toward a high-glucose energy use. This shift mechanism is still fully functional in a diabetic heart cell, but because the underlying diabetes shifts the cellular metabolism to a primarily fatty-acid-based energy use, even a normally functioning hypoxia-induced cascade does not lead to full glucose metabolism or normal cellular repair.
So sleep apnea might serve a useful function in instigating heart tissue repair in cells. This suggests that sleep apnea and diabetes are not just frequently found together, but one condition may be causing the other.
After discussing some of the possible evolutionary drivers for co-adaptation of sleep apnea and diabetes, we examine some of the epigenetic marks associated with the two conditions, laying the groundwork for a better understanding of the underlying etiology.
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Lichens as bioindicators for air quality in the Intermountain West - creating a model for large-scale monitoring
Smith, Hayden; Leavitt, Steve (Brigham Young University)
Faculty Advisor: Leavitt, Steve (College of Life Sciences, Biology)
Brigham Young University's Lichen Air Quality Biomonitoring Program (Herbarium of Non-Vascular Cryptogams) represents one of the largest and longest-running lichen biomonitoring programs worldwide, with nearly 500 permanent reference plots distributed across the Intermountain West. At each reference site, sensitive indicator lichens are selected for elemental analyses of 25 potential pollutants, with the aim of subsequent resampling every five to 15 years for ongoing evaluations of ecological health. Using elemental analysis (EA) data from the past 30 years, a model for large-scale monitoring has been developed with the aim to (i) improve interpretation of air quality using lichen bioindicators, (ii) establish a framework to integrate future EA samples for comparison to historical data, and (iii) develop a platform in the future to more effectively share these data with land management agencies, research groups, and the broader public. The model will be field-tested with new EA samples collected along the Wasatch Front.
Faculty Advisor: Leavitt, Steve (College of Life Sciences, Biology)
Brigham Young University's Lichen Air Quality Biomonitoring Program (Herbarium of Non-Vascular Cryptogams) represents one of the largest and longest-running lichen biomonitoring programs worldwide, with nearly 500 permanent reference plots distributed across the Intermountain West. At each reference site, sensitive indicator lichens are selected for elemental analyses of 25 potential pollutants, with the aim of subsequent resampling every five to 15 years for ongoing evaluations of ecological health. Using elemental analysis (EA) data from the past 30 years, a model for large-scale monitoring has been developed with the aim to (i) improve interpretation of air quality using lichen bioindicators, (ii) establish a framework to integrate future EA samples for comparison to historical data, and (iii) develop a platform in the future to more effectively share these data with land management agencies, research groups, and the broader public. The model will be field-tested with new EA samples collected along the Wasatch Front.
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Prophylactic Treatment of Post-Traumatic Stress Disorder with Mifepristone and Propranolol
Boyce, Zach; Smith, Calvin; Martin, Ashlyn; Ketch, Yuko; Dugan, James; Wright, Cole (Brigham Young University)
Faculty Advisor: Jeffrey, Edwards (Brigham Young University, Physiology and Developmental Biology)
Post-traumatic stress disorder (PTSD) is a complex psychological disorder that affects about 1 of 4 individuals after a stressful/traumatic experience. One common model to induce PTSD in rats is social defeat (SD) combined with chronic light exposure. First, we screened rats for natural anxiety to use in the SD protocol. Next, elevated plus maze (EPM) and light-dark transition (LDT) tests were used to detect anxious behavior after SD. The SD protocol induced significant anxious behavior when compared to controls. Next, we performed long-term potentiation (LTP) field electrophysiology synaptic plasticity physiology experiments in brain slices of the ventral hippocampus (VH) and basolateral amygdala (BLA), regions known to have altered enhanced plasticity in PTSD. SD significantly increased LTP in the VH (~25% greater than control) and BLA (~35% greater than control). To determine whether a prophylactic treatment could prevent the physiological changes of PTSD, we simultaneously administered two drugs at 10 mg/kg doses by intraperitoneal injection one week prior to and for the duration of SD. The first, propranolol, is a beta-adrenergic receptor antagonist, and the second, mifepristone, is a glucocorticoid receptor antagonist; thus, treatment would target the action of stress hormones altered in PTSD. To determine whether a prophylactic treatment could prevent the physiological changes of PTSD, propranolol and mifepristone, antagonists of two stress receptors, were simultaneously administered at 10 mg/kg doses by intraperitoneal (IP) injection one week prior to and for the duration of SThese drugs significantly decreased LTP in the VH and BLA back to near-control levels while SD rats with vehicle injections still had elevated LTP. However, SD drug-treated rats did not show significant reductions in anxious behavior compared to non-injected SD rats and also exhibited significantly more anxious behavior than control rats, suggesting the IP injection induced added stress. Next, we used rtPCR to examine gene expression of drug targets and plasticity markers to determine potential mechanisms for observed LTP changes. In both the VH and BLA, SD was associated with a significant decrease in glucocorticoid and mineralocorticoid receptor expression, which was restored to control levels under drug treatment. Overall, our data suggest that propranolol and mifepristone together may be a potential prophylactic treatment for preventing PTSD through a mechanism likely mediated by glucocorticoid/mineralocorticoid receptors.
Faculty Advisor: Jeffrey, Edwards (Brigham Young University, Physiology and Developmental Biology)
Post-traumatic stress disorder (PTSD) is a complex psychological disorder that affects about 1 of 4 individuals after a stressful/traumatic experience. One common model to induce PTSD in rats is social defeat (SD) combined with chronic light exposure. First, we screened rats for natural anxiety to use in the SD protocol. Next, elevated plus maze (EPM) and light-dark transition (LDT) tests were used to detect anxious behavior after SD. The SD protocol induced significant anxious behavior when compared to controls. Next, we performed long-term potentiation (LTP) field electrophysiology synaptic plasticity physiology experiments in brain slices of the ventral hippocampus (VH) and basolateral amygdala (BLA), regions known to have altered enhanced plasticity in PTSD. SD significantly increased LTP in the VH (~25% greater than control) and BLA (~35% greater than control). To determine whether a prophylactic treatment could prevent the physiological changes of PTSD, we simultaneously administered two drugs at 10 mg/kg doses by intraperitoneal injection one week prior to and for the duration of SD. The first, propranolol, is a beta-adrenergic receptor antagonist, and the second, mifepristone, is a glucocorticoid receptor antagonist; thus, treatment would target the action of stress hormones altered in PTSD. To determine whether a prophylactic treatment could prevent the physiological changes of PTSD, propranolol and mifepristone, antagonists of two stress receptors, were simultaneously administered at 10 mg/kg doses by intraperitoneal (IP) injection one week prior to and for the duration of SThese drugs significantly decreased LTP in the VH and BLA back to near-control levels while SD rats with vehicle injections still had elevated LTP. However, SD drug-treated rats did not show significant reductions in anxious behavior compared to non-injected SD rats and also exhibited significantly more anxious behavior than control rats, suggesting the IP injection induced added stress. Next, we used rtPCR to examine gene expression of drug targets and plasticity markers to determine potential mechanisms for observed LTP changes. In both the VH and BLA, SD was associated with a significant decrease in glucocorticoid and mineralocorticoid receptor expression, which was restored to control levels under drug treatment. Overall, our data suggest that propranolol and mifepristone together may be a potential prophylactic treatment for preventing PTSD through a mechanism likely mediated by glucocorticoid/mineralocorticoid receptors.
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Loading a Novel Anti-biofilm Compound into Polyurethane Foam for Use in Negative Pressure Wound Therapy
Rawson, Kaden; Nueberger, Travis; Looper, Ryan; Sebahar, Paul; Williams, Dustin (University of Utah)
Faculty Advisor: Williams, Dustin (Engineering, Bioengineering)
Negative pressure wound therapy (NPWT) is commonly used to treat high energy, traumatic battlefield-related injuries, typically caused by an explosion. NPWT may be applied in the field at the time of injury or in the operating room as a therapeutic measure. Wounds are susceptible to contamination from the soil, which contains high amounts of bacteria (>10^9 colony forming units (CFU)/g of material). Greater than 99% of wild-type bacteria favor the biofilm phenotype in the natural world. Biofilms are aggregates of bacteria that are more resistant to traditional antibiotics due to their altered phenotypic and metabolic expressions. Thus, developed biofilms can potentially contaminate these wounds and lead to chronic infection. Furthermore, the lattice structure of polyurethane (PU) foam used in NPWT can potentially harbor and encourage increased biofilm growth. Since the introduction of NPWT as a standard of care for soldiers in 2004, "superficial and deep infections of soft tissue remain a clinical concern after sustaining combat-related trauma [while] using NPWT." To date, GRANUFOAM Silver by KCI is the only variation of PU foam for NPWT that possesses any degree of antimicrobial efficacy. However, silver nanoparticles are minimally effective against biofilms. Thus, the goal of this project is to develop a PU foam that is loaded with a biofilm-specific antimicrobial compound, CZ-01179 in order to decrease the rate of infection when NPWT is utilized in the field of battle.
To date, two prototypes have been developed: One prototype (V1) relies on THF and H2O to coat the Pu foam with CZ-01179 while the second prototype (V2) relies on a hydrogel scaffold to provide a sustained release of CZ-01179 over 24 hours. V1 has been shown to reduce MRSA AND A. baumanii by 7 Log10 CFU during in vitro dilution testing compared to a 1 Log10 reduction produced by GRANUFOAM Silver.
Faculty Advisor: Williams, Dustin (Engineering, Bioengineering)
Negative pressure wound therapy (NPWT) is commonly used to treat high energy, traumatic battlefield-related injuries, typically caused by an explosion. NPWT may be applied in the field at the time of injury or in the operating room as a therapeutic measure. Wounds are susceptible to contamination from the soil, which contains high amounts of bacteria (>10^9 colony forming units (CFU)/g of material). Greater than 99% of wild-type bacteria favor the biofilm phenotype in the natural world. Biofilms are aggregates of bacteria that are more resistant to traditional antibiotics due to their altered phenotypic and metabolic expressions. Thus, developed biofilms can potentially contaminate these wounds and lead to chronic infection. Furthermore, the lattice structure of polyurethane (PU) foam used in NPWT can potentially harbor and encourage increased biofilm growth. Since the introduction of NPWT as a standard of care for soldiers in 2004, "superficial and deep infections of soft tissue remain a clinical concern after sustaining combat-related trauma [while] using NPWT." To date, GRANUFOAM Silver by KCI is the only variation of PU foam for NPWT that possesses any degree of antimicrobial efficacy. However, silver nanoparticles are minimally effective against biofilms. Thus, the goal of this project is to develop a PU foam that is loaded with a biofilm-specific antimicrobial compound, CZ-01179 in order to decrease the rate of infection when NPWT is utilized in the field of battle.
To date, two prototypes have been developed: One prototype (V1) relies on THF and H2O to coat the Pu foam with CZ-01179 while the second prototype (V2) relies on a hydrogel scaffold to provide a sustained release of CZ-01179 over 24 hours. V1 has been shown to reduce MRSA AND A. baumanii by 7 Log10 CFU during in vitro dilution testing compared to a 1 Log10 reduction produced by GRANUFOAM Silver.
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Micropropagation of Lepidium ostleri, an edaphic endemic plant species
DeNittis, Alyson; Larson, Joseph; Perez, June; Kopp, Olga R. (Utah Valley University)
Faculty Advisor: Kopp, Olga (Utah Valley University, Biology)
Lepidium ostleri (Ostler's peppergrass) is an edaphic endemic plant species restricted to Ordovician limestone outcrops of the San Francisco Mountains in western Utah. L. ostleri is a species of conservation concern due to its restricted range and proximity to modern mining operations. The purpose of this research is to develop a micropropagation protocol to produce mature plants for population augmentation and introduction to support conservation efforts. De novo shoot organogenic response in tissue explants was highest with various concentrations and combinations of 6-Benzylaminopurine (BAP) and indole-3-acetic acid (IAA). In vitro and ex vitro rooting experiments were conducted on micropropagated plantlets supporting adequate number of shoots, with highest success in pulse treatments of indole-3 butyric acid (IBA). Plantlets were then acclimated to external environments for further propagation. Additional effects of different plant growth regulators, media, and growth conditions will be described. Methods for organogenesis for L. ostleri has not been published and this represents the first known instance of successful micropropagation of this rare plant species. Establishing a micropropagation protocol for L. ostleri provides valuable information for potential restoration or relocation efforts.
Faculty Advisor: Kopp, Olga (Utah Valley University, Biology)
Lepidium ostleri (Ostler's peppergrass) is an edaphic endemic plant species restricted to Ordovician limestone outcrops of the San Francisco Mountains in western Utah. L. ostleri is a species of conservation concern due to its restricted range and proximity to modern mining operations. The purpose of this research is to develop a micropropagation protocol to produce mature plants for population augmentation and introduction to support conservation efforts. De novo shoot organogenic response in tissue explants was highest with various concentrations and combinations of 6-Benzylaminopurine (BAP) and indole-3-acetic acid (IAA). In vitro and ex vitro rooting experiments were conducted on micropropagated plantlets supporting adequate number of shoots, with highest success in pulse treatments of indole-3 butyric acid (IBA). Plantlets were then acclimated to external environments for further propagation. Additional effects of different plant growth regulators, media, and growth conditions will be described. Methods for organogenesis for L. ostleri has not been published and this represents the first known instance of successful micropropagation of this rare plant species. Establishing a micropropagation protocol for L. ostleri provides valuable information for potential restoration or relocation efforts.
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Positioning Nucleosomes with 601 DNA Sequence to Restore GFP Expression
Hales, Emily; Lundgren, Jane; Carter, John; Kempton, Colton; Johnson, Steven (Brigham Young University)
Faculty Advisor: Johnson, Steven (Brigham Young University, Molecular and Microbiology)
The mechanisms of transgene silencing in C. elegans are poorly understood, despite the importance of the nematode as a model for genetic research. Insertion of a transgene led to the expression of GFP in both the body wall and pharyngeal muscle cells of C. elegans as expected. However, subsequent generations stopped expressing body wall GFP. To reverse silencing, we have flanked the enhancers responsible for GFP expression with 601 sequences. The 601 sequence strongly positions nucleosomes. We hypothesize that this positioning will eliminate transgenerational gene silencing of body wall GFP.
Faculty Advisor: Johnson, Steven (Brigham Young University, Molecular and Microbiology)
The mechanisms of transgene silencing in C. elegans are poorly understood, despite the importance of the nematode as a model for genetic research. Insertion of a transgene led to the expression of GFP in both the body wall and pharyngeal muscle cells of C. elegans as expected. However, subsequent generations stopped expressing body wall GFP. To reverse silencing, we have flanked the enhancers responsible for GFP expression with 601 sequences. The 601 sequence strongly positions nucleosomes. We hypothesize that this positioning will eliminate transgenerational gene silencing of body wall GFP.
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Optimal chemotherapeutic combination of 9 putative natural compounds
Berlin, Ian; Kenealey, Jason. (Brigham Young University)
Faculty Advisor: Kenealey, Jason (Life Science; Nutrition, Dietetics, and Food Science)
Prostate cancer accounts for 9.9% of all new cancer cases in the United States annually, and thought it has high 5-year survival rate of 98%, but its prognosis changes if the cancer becomes drug resistant or metastases. Natural compounds are often used and studied for their potential chemotherapeutic effects or their sensitizing effects which increases the cancer cells susceptibility to treatment. Traditional Chinese medicine is a common source for finding bioactive small molecules which may have chemotherapeutic effects. This study focused on 9 putative natural compounds and their effectiveness of treating PC-3 prostate cancer cells. First their IC50s were calculated and then used in Mixture Design Response Surface Methodology (MDRSM) to determine the optimal mixture ratio and used in Chou Talalay statistical analysis to determine if combination effects were synergistic, antagonistic or additive. The compounds used in ascending order starting at the most potent or lowest IC50 to highest; Triptolide, .01819uM (Ttd), Shikonin, .6002uM (Shk), Curcumin 20.83uM (Cur), Emodin, 57.38uM (Em), Wogonin, 97.87uM (Wo) Berberine, 101.4uM (BB), Silibinin, 106.2uM (or Silybin) (Sy), Epigallocatechin gallate, 272.6uM (EGCG), and beta Elemene, 304.3uM (beta-E). Emodin, Silibinin and EGCG all appeared to act primarily via cell cycle inhibition and their effectiveness was found to increase in combination with other small molecules. The ideal combination was provided a multi-faced approach reduce cell viability which suggests it may help treat prostate cancer cells in vivo either in tandem or alone.
Faculty Advisor: Kenealey, Jason (Life Science; Nutrition, Dietetics, and Food Science)
Prostate cancer accounts for 9.9% of all new cancer cases in the United States annually, and thought it has high 5-year survival rate of 98%, but its prognosis changes if the cancer becomes drug resistant or metastases. Natural compounds are often used and studied for their potential chemotherapeutic effects or their sensitizing effects which increases the cancer cells susceptibility to treatment. Traditional Chinese medicine is a common source for finding bioactive small molecules which may have chemotherapeutic effects. This study focused on 9 putative natural compounds and their effectiveness of treating PC-3 prostate cancer cells. First their IC50s were calculated and then used in Mixture Design Response Surface Methodology (MDRSM) to determine the optimal mixture ratio and used in Chou Talalay statistical analysis to determine if combination effects were synergistic, antagonistic or additive. The compounds used in ascending order starting at the most potent or lowest IC50 to highest; Triptolide, .01819uM (Ttd), Shikonin, .6002uM (Shk), Curcumin 20.83uM (Cur), Emodin, 57.38uM (Em), Wogonin, 97.87uM (Wo) Berberine, 101.4uM (BB), Silibinin, 106.2uM (or Silybin) (Sy), Epigallocatechin gallate, 272.6uM (EGCG), and beta Elemene, 304.3uM (beta-E). Emodin, Silibinin and EGCG all appeared to act primarily via cell cycle inhibition and their effectiveness was found to increase in combination with other small molecules. The ideal combination was provided a multi-faced approach reduce cell viability which suggests it may help treat prostate cancer cells in vivo either in tandem or alone.
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Age-Dependent Molecular Effects of Cyclin-Dependent Kinase Inhibitors on β-cell Proliferation
Jensen, Daelin; Aitken, Talon; Baxter, Melanie (Brigham Young University)
Faculty Advisor: Tessem, Jeffery (Brigham Young University; Nutrition, Dietetics, and Food Science)
As of 2017, over 400 million people were diagnosed with diabetes mellitus. This is becoming a worldwide concern as the number of people affected by diabetes is growing at an alarming rate. Functional pancreatic β-cell mass is responsible for maintaining healthy blood glucose levels through the production of insulin. A hallmark of both type 1 and type 2 diabetes is a relative or absolute loss of functional β-cell mass and, consequently, decreased insulin production. Two possible approaches for replenishing the β-cells are: 1) replacement through cadaveric donors and 2) regeneration of endogenous β-cells. A major impediment to these approaches is that aged β-cells are refractory to genes that are known to induce proliferation in young β-cells. It is currently unknown why aged β-cells are refractory. . We hypothesized that age-dependent changes to the proliferative capacity of β-cells are influenced by increasing levels of cyclin-dependent kinase inhibitors (CDKI). CDKI's bind to cyclin-dependent kinases, effectively halting the cell cycle and proliferation. Here, we demonstrate the expression of the Ink4 and Cip/Kip families of CDKI's by mRNA and protein expression in five week old and five month old Wistar rat β-cells. Greater understanding of the proliferative mechanisms of the β-cell will allow greater application of the aforementioned treatments.
Faculty Advisor: Tessem, Jeffery (Brigham Young University; Nutrition, Dietetics, and Food Science)
As of 2017, over 400 million people were diagnosed with diabetes mellitus. This is becoming a worldwide concern as the number of people affected by diabetes is growing at an alarming rate. Functional pancreatic β-cell mass is responsible for maintaining healthy blood glucose levels through the production of insulin. A hallmark of both type 1 and type 2 diabetes is a relative or absolute loss of functional β-cell mass and, consequently, decreased insulin production. Two possible approaches for replenishing the β-cells are: 1) replacement through cadaveric donors and 2) regeneration of endogenous β-cells. A major impediment to these approaches is that aged β-cells are refractory to genes that are known to induce proliferation in young β-cells. It is currently unknown why aged β-cells are refractory. . We hypothesized that age-dependent changes to the proliferative capacity of β-cells are influenced by increasing levels of cyclin-dependent kinase inhibitors (CDKI). CDKI's bind to cyclin-dependent kinases, effectively halting the cell cycle and proliferation. Here, we demonstrate the expression of the Ink4 and Cip/Kip families of CDKI's by mRNA and protein expression in five week old and five month old Wistar rat β-cells. Greater understanding of the proliferative mechanisms of the β-cell will allow greater application of the aforementioned treatments.
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Use of a Portable Handheld X-Ray Fluorescence Unit (pXRF) to Measure Alteration in Exhumed Fault Zones: Implications for Hydrologic Rock Properties and Injection Induced Seismicity
Paulding, Anna (Utah State University)
Faculty Advisor: Bradbury, Kelly (College of Science, Geosciences Department)
A dramatic increase in seismicity has occurred in the midcontinent region since 2009 (Rubinstein and Mahani, 2015), causing public concern for the stability of infrastructure and buildings. Several studies have directly linked this seismicity to the reactivation of buried fault systems near the Paleozoic sedimentary bedrock-Precambrian crystalline basement contact as a result of high volumes of injection of wastewater produced by the oil and gas industry (Ellsworth, 2013; Keranen et al., 2013).
The reactivation of fault zones due to fluid injection is not only influenced by injection rates but also by the ability of fluids to migrate along or across the contact, which is controlled by the rock properties and geologic setting. To better understand the rock property variations that may occur along the nonconformity interface, we use an outcrop analog site of an exhumed fault near Gunnison, Colorado. My undergraduate research focuses on using a portable handheld X-Ray Fluorescence Unit (pXRF) as a tool to measure compositional variations in outcrop. To directly compare data, a calibration using 16 USGS Concentration Standards as well as 12 analog samples will be used to create a calibration optimized for this specific suite of rocks which informs the accuracy of in-situ field data measurements against laboratory measurements of powdered samples, influencing how future pXRF measurements can be analyzed. Micro-scale variations of major and trace element concentrations reflect alteration and related fluid-rock interactions and may serve as a proxy for fluid migration along or across faulted sections of a nonconformity interface. I propose that calibrated pXRF data and whole rock XRF data is a useful tool for understanding the nature and degree of rock alteration in fault zones and across analog sites nonconformity interface. These data can aid in a more broad understanding of how pXRF data can be used in the field to characterize the nonconformity interface and fault zones.
Faculty Advisor: Bradbury, Kelly (College of Science, Geosciences Department)
A dramatic increase in seismicity has occurred in the midcontinent region since 2009 (Rubinstein and Mahani, 2015), causing public concern for the stability of infrastructure and buildings. Several studies have directly linked this seismicity to the reactivation of buried fault systems near the Paleozoic sedimentary bedrock-Precambrian crystalline basement contact as a result of high volumes of injection of wastewater produced by the oil and gas industry (Ellsworth, 2013; Keranen et al., 2013).
The reactivation of fault zones due to fluid injection is not only influenced by injection rates but also by the ability of fluids to migrate along or across the contact, which is controlled by the rock properties and geologic setting. To better understand the rock property variations that may occur along the nonconformity interface, we use an outcrop analog site of an exhumed fault near Gunnison, Colorado. My undergraduate research focuses on using a portable handheld X-Ray Fluorescence Unit (pXRF) as a tool to measure compositional variations in outcrop. To directly compare data, a calibration using 16 USGS Concentration Standards as well as 12 analog samples will be used to create a calibration optimized for this specific suite of rocks which informs the accuracy of in-situ field data measurements against laboratory measurements of powdered samples, influencing how future pXRF measurements can be analyzed. Micro-scale variations of major and trace element concentrations reflect alteration and related fluid-rock interactions and may serve as a proxy for fluid migration along or across faulted sections of a nonconformity interface. I propose that calibrated pXRF data and whole rock XRF data is a useful tool for understanding the nature and degree of rock alteration in fault zones and across analog sites nonconformity interface. These data can aid in a more broad understanding of how pXRF data can be used in the field to characterize the nonconformity interface and fault zones.
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Cancer Data Exploration for the Public
Payne, Samuel; Paquette, Teancum; Lindgren, Caleb (Brigham Young University)
Faculty Advisor: Payne, Samuel (Brigham Young University, Life Sciences)
The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) generates comprehensive proteogenomic data for cancer cohorts. Our goal is to bring CPTAC data to researchers and the general public. A major difficulty in accomplishing this is the large amount of variability in the programming capabilities in the public. As a solution, we created a set of interactive tutorials that instructs users on exploring CPTAC data in a way that even novice programmers can understand. However, these tutorials still require software installation, which can be complicated. In order to empower more people to confidently use, access and analyze cancer data, we are making our tutorials accessible without any installation. We plan to do this by hosting the tutorials directly using a tool called Binder. In the end this project will not only improve the quality of user experience with CPTAC, but also improve the quality of their experience accessing a vast amount of cancer data.
Faculty Advisor: Payne, Samuel (Brigham Young University, Life Sciences)
The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) generates comprehensive proteogenomic data for cancer cohorts. Our goal is to bring CPTAC data to researchers and the general public. A major difficulty in accomplishing this is the large amount of variability in the programming capabilities in the public. As a solution, we created a set of interactive tutorials that instructs users on exploring CPTAC data in a way that even novice programmers can understand. However, these tutorials still require software installation, which can be complicated. In order to empower more people to confidently use, access and analyze cancer data, we are making our tutorials accessible without any installation. We plan to do this by hosting the tutorials directly using a tool called Binder. In the end this project will not only improve the quality of user experience with CPTAC, but also improve the quality of their experience accessing a vast amount of cancer data.
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Anti-Tumor Activity of Chalcone Derivatives
Allen, Brian; Covey, Tracy; Davies, Don; Eccles, Nick; Farnsworth, Brian; Ferguson, Parker; Hart, Sierra; Lowder, Jordan (Weber State University)
Faculty Advisor: Davies, Don (Weber State University, Chemistry and Biochemistry); Covey, Tracy (Weber State University, Chemistry and Biochemsitry)
Chalcones refer to biological molecules with the structure trans 1,3-diphenylprop-2-en-1-one. Biological chalcones and chalcone derivatives display anti-tumor, anti-fungal, anti-inflammatory and antibiotic properties. To understand the role of the chalcone structure in tumor cessation, derivatives to the original chalcone were synthesized using aldol condensation reactions. HeLa and HEK-293 cells were treated with the synthesized chalcone and an LD50, or the concentration of chalcone required to kill half of the cells, was calculated. The LD50 was then used to determine the efficiency of the chalcone derivative. Correlations between the structure and activity suggest that a Michael reaction occurs at the cell and indicate that that an aromatic ring at C3 is likely necessary. Further research will help determine the structures of more cytotoxic compounds.
Faculty Advisor: Davies, Don (Weber State University, Chemistry and Biochemistry); Covey, Tracy (Weber State University, Chemistry and Biochemsitry)
Chalcones refer to biological molecules with the structure trans 1,3-diphenylprop-2-en-1-one. Biological chalcones and chalcone derivatives display anti-tumor, anti-fungal, anti-inflammatory and antibiotic properties. To understand the role of the chalcone structure in tumor cessation, derivatives to the original chalcone were synthesized using aldol condensation reactions. HeLa and HEK-293 cells were treated with the synthesized chalcone and an LD50, or the concentration of chalcone required to kill half of the cells, was calculated. The LD50 was then used to determine the efficiency of the chalcone derivative. Correlations between the structure and activity suggest that a Michael reaction occurs at the cell and indicate that that an aromatic ring at C3 is likely necessary. Further research will help determine the structures of more cytotoxic compounds.
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Antimicrobial Activity of Artemisia tridentata
Wasden, Kayla; Suisse, David; Kaundal, Amita (faculty mentor) (Utah State University)
Faculty Advisor: Kaundal, Amita (College of Agriculture and Applied Sciences; Plants, Soils, and Climate Department)
Many plants secrete substances to create a more favorable environment, including chemicals that kill pathogenic microbes or competing plants. Artemisia tridentata, also known as "Big Sagebrush," is prevalent in the Rocky Mountain region of the United States and is known to have antimicrobial capabilities. We will study the potential antimicrobial activity of Artemisia tridentata.
Studies report that chemicals released by the leaves and branches of A. tridentata affect bacteria native to deer rumen. Another study showed that 27 actinomycetes (anaerobic bacteria that form colonies) strains found in the rhizosphere of A. tridentata demonstrated antibacterial activities when tested on E. coli, Bacillus subtilis and Staphylococcus aureus. Native Americans traditionally used A. tridentata to relieve stomach pain, colds, coughs, sore eyes, snake bites and as an insect repellent. Researchers found several compounds, including flavonoids, that can affect antimicrobial activity. Articles regarding antimicrobial activities in A. tridentata were published between 1967 and 2004. With the chronological gaps and considering the progress that biological and molecular technology has made in recent years, knowledge of the chemicals released by A. tridentata lies largely untapped. In this study, we will investigate the antimicrobial activities of the leaves, stem, roots, and flowers of A. tridentata initially by the agar well diffusion method and followed by validating with the agar disk diffusion method. We will check the antimicrobial activity of the extract from different plant parts of A. tridentata on common bacteria such as E. coli, Bacillus subtilis, and some Pseudomonas spp. of plant pathogens.
The knowledge obtained from this research will further help in the identification and characterization of the secondary metabolites or chemicals involved in antimicrobial activity of sagebrush. Medicinal plants provide a healthy, natural alternative to conventional medication, and may lead to new insights on antibiotics and pharmaceuticals. Besides, Artemisia tridentata is a plant native to Utah and Idaho. It grows everywhere in the surrounding area, making it inexpensive (free) to produce.
Faculty Advisor: Kaundal, Amita (College of Agriculture and Applied Sciences; Plants, Soils, and Climate Department)
Many plants secrete substances to create a more favorable environment, including chemicals that kill pathogenic microbes or competing plants. Artemisia tridentata, also known as "Big Sagebrush," is prevalent in the Rocky Mountain region of the United States and is known to have antimicrobial capabilities. We will study the potential antimicrobial activity of Artemisia tridentata.
Studies report that chemicals released by the leaves and branches of A. tridentata affect bacteria native to deer rumen. Another study showed that 27 actinomycetes (anaerobic bacteria that form colonies) strains found in the rhizosphere of A. tridentata demonstrated antibacterial activities when tested on E. coli, Bacillus subtilis and Staphylococcus aureus. Native Americans traditionally used A. tridentata to relieve stomach pain, colds, coughs, sore eyes, snake bites and as an insect repellent. Researchers found several compounds, including flavonoids, that can affect antimicrobial activity. Articles regarding antimicrobial activities in A. tridentata were published between 1967 and 2004. With the chronological gaps and considering the progress that biological and molecular technology has made in recent years, knowledge of the chemicals released by A. tridentata lies largely untapped. In this study, we will investigate the antimicrobial activities of the leaves, stem, roots, and flowers of A. tridentata initially by the agar well diffusion method and followed by validating with the agar disk diffusion method. We will check the antimicrobial activity of the extract from different plant parts of A. tridentata on common bacteria such as E. coli, Bacillus subtilis, and some Pseudomonas spp. of plant pathogens.
The knowledge obtained from this research will further help in the identification and characterization of the secondary metabolites or chemicals involved in antimicrobial activity of sagebrush. Medicinal plants provide a healthy, natural alternative to conventional medication, and may lead to new insights on antibiotics and pharmaceuticals. Besides, Artemisia tridentata is a plant native to Utah and Idaho. It grows everywhere in the surrounding area, making it inexpensive (free) to produce.
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CD5 knockout mice display reduced ethanol consumption and resistance to ethanol induced sedation
Baptista, Gabriela; Payne, Andrew; Obray, J Daniel; Yorgason, Jordan; Weber, K Scott; Steffensen, Scott (Brigham Young University)
Faculty Advisor: Steffensen, Scott (Family, Home, and Social Sciences, Psychology)
Cluster of differentiation 5 (CD5) is expressed in both T and B cells. CD5 has been found to display an altered expression profile following chronic ethanol use and during ethanol withdrawal. Specifically, the number of CD5+ B cells is reduced during withdrawal while the number of T cells is increased. Given the apparent sensitivity of these cells to ethanol and recent research suggesting that some ethanol effects are accounted for by neuroimmune interactions we assessed drinking behavior and ethanol induced sedation in CD5 knockout (KO) mice. We found that CD5 KO mice display decreased ethanol consumption as compared with wild-type controls and that ethanol consumption does not increase with repeated exposure in CD5 KO mice. Additionally, CD5 KO mice displayed considerable resistance to the sedating effects of ethanol. Further studies are underway to assess whether there are baseline differences in dopamine dynamics within the mesolimbic pathway between CD5 KO mice and wild-type controls as well as to whether neurons in the mesolimbic pathway differ in their response to ethanol in CD5 KO mice.
Faculty Advisor: Steffensen, Scott (Family, Home, and Social Sciences, Psychology)
Cluster of differentiation 5 (CD5) is expressed in both T and B cells. CD5 has been found to display an altered expression profile following chronic ethanol use and during ethanol withdrawal. Specifically, the number of CD5+ B cells is reduced during withdrawal while the number of T cells is increased. Given the apparent sensitivity of these cells to ethanol and recent research suggesting that some ethanol effects are accounted for by neuroimmune interactions we assessed drinking behavior and ethanol induced sedation in CD5 knockout (KO) mice. We found that CD5 KO mice display decreased ethanol consumption as compared with wild-type controls and that ethanol consumption does not increase with repeated exposure in CD5 KO mice. Additionally, CD5 KO mice displayed considerable resistance to the sedating effects of ethanol. Further studies are underway to assess whether there are baseline differences in dopamine dynamics within the mesolimbic pathway between CD5 KO mice and wild-type controls as well as to whether neurons in the mesolimbic pathway differ in their response to ethanol in CD5 KO mice.
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Basal diet, green tea extract and gut microbiome interactions in a mouse multi-generation study.
Bartlett, Ashley; Phatak, Sumira; Hintze, Korry; Benninghoff, Abby (Utah State University)
Faculty Advisor: Benninghoff, Abby (College of Agriculture and Applied Sciences; Animal, Dairy, and Veterinary Sciences Department)
The gut microbiome modulates various physiological functions related to cancer development including inflammation, cell proliferation, apoptosis, and angiogenesis. Patients with inflammatory bowel disease have a microbiome distinct from healthy controls with consistent observations of reduced gut biomass, decreased diversity within the community, and altered relative abundance. Although a consensus cancer-related microbiome has not been identified, several pathogenic species play an instrumental role in the progression of colitis and tumorigenesis, including: Streptococcus bovis, Helicobacter pylori, Enterococcus faecalis, Clostridium septicum, and Escherichia coli. Gut microbial composition is highly responsive to diet and inadequate intake of micronutrients is a critical feature of the Western dietary pattern. Gut dysbiosis has been proposed to further limit mineral uptake and impair vitamin synthesis, predisposing the host to micronutrient deficiency. Dietary bioactives, such as those in green tea, may function as a mediator between the gut microbiome and basal diet to ultimately prevent colitis associated colorectal cancer (CAC). The overarching objective of our work is to determine the impact of ancestral or multi-generational consumption of the total Western diet (TWD) in a murine model of CAC. Our previous work is the first to investigate how diet induced transgenerational inheritance affects CAC outcome. Our data suggested that multigenerational patterns of exposure to the TWD altered both phenotype and gene expression in third generation offspring. Supplementation with green tea appeared to be most promising after consumption of TWD for multiple generations. Considering that gut microbes are inherited maternally after colonization during vaginal birth, the gut microbiome is a missing piece in this disease model puzzle. The hypothesis of our current project is to investigate whether intake of TWD influences the transmission of microbes and whether CAC outcome is reflected by altered gut microbial composition. Based on other work, we expect the healthy control to possess an abundance of varied bacterial taxa that maintain protective epithelial barrier function and overall homeostasis. On the other hand, a high fat diet would promote increased intestinal permeability, a substantial shift at the phyla level, and increased production of pro-inflammatory cytokines. After TWD consumption, we expect an overall negative phenotypic outcome within the gut microbiome, that includes a breakdown of the epithelial barrier and introduction of pathogenic bacteria. These harmful bacteria tend to thrive on simple sugars that are common in the Western dietary pattern and tend to produce metabolites known as endotoxins that promote dysbiosis.
Faculty Advisor: Benninghoff, Abby (College of Agriculture and Applied Sciences; Animal, Dairy, and Veterinary Sciences Department)
The gut microbiome modulates various physiological functions related to cancer development including inflammation, cell proliferation, apoptosis, and angiogenesis. Patients with inflammatory bowel disease have a microbiome distinct from healthy controls with consistent observations of reduced gut biomass, decreased diversity within the community, and altered relative abundance. Although a consensus cancer-related microbiome has not been identified, several pathogenic species play an instrumental role in the progression of colitis and tumorigenesis, including: Streptococcus bovis, Helicobacter pylori, Enterococcus faecalis, Clostridium septicum, and Escherichia coli. Gut microbial composition is highly responsive to diet and inadequate intake of micronutrients is a critical feature of the Western dietary pattern. Gut dysbiosis has been proposed to further limit mineral uptake and impair vitamin synthesis, predisposing the host to micronutrient deficiency. Dietary bioactives, such as those in green tea, may function as a mediator between the gut microbiome and basal diet to ultimately prevent colitis associated colorectal cancer (CAC). The overarching objective of our work is to determine the impact of ancestral or multi-generational consumption of the total Western diet (TWD) in a murine model of CAC. Our previous work is the first to investigate how diet induced transgenerational inheritance affects CAC outcome. Our data suggested that multigenerational patterns of exposure to the TWD altered both phenotype and gene expression in third generation offspring. Supplementation with green tea appeared to be most promising after consumption of TWD for multiple generations. Considering that gut microbes are inherited maternally after colonization during vaginal birth, the gut microbiome is a missing piece in this disease model puzzle. The hypothesis of our current project is to investigate whether intake of TWD influences the transmission of microbes and whether CAC outcome is reflected by altered gut microbial composition. Based on other work, we expect the healthy control to possess an abundance of varied bacterial taxa that maintain protective epithelial barrier function and overall homeostasis. On the other hand, a high fat diet would promote increased intestinal permeability, a substantial shift at the phyla level, and increased production of pro-inflammatory cytokines. After TWD consumption, we expect an overall negative phenotypic outcome within the gut microbiome, that includes a breakdown of the epithelial barrier and introduction of pathogenic bacteria. These harmful bacteria tend to thrive on simple sugars that are common in the Western dietary pattern and tend to produce metabolites known as endotoxins that promote dysbiosis.
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Blue Streak on Uca Pugnax
Anderson, Lars; Baldwin, Haley; Christensen, Ben; Walker, Austen (Brigham Young University)
Faculty Advisor: Griffen, Blaine (Brigham Young University, Life Sciences)
This research looks at the blue coloration on uca pugnax crab carapace above the mouth and between the eyestalks and associates the coloration to the behavior, sexual maturity, and size of the crab, as well as the detection of metals in their environment. Up to ten crabs were photographed within twenty five isolated sites with the objective of gathering a high range of color difference among the uca pugnax. The photos of the crabs were set to match the same scale of light and RGB as to not have interference from external factors such as sunlight or overcast weather. The shade of blue on the carapace provides information about the surrounding environment where the uca pugnax are found.
Faculty Advisor: Griffen, Blaine (Brigham Young University, Life Sciences)
This research looks at the blue coloration on uca pugnax crab carapace above the mouth and between the eyestalks and associates the coloration to the behavior, sexual maturity, and size of the crab, as well as the detection of metals in their environment. Up to ten crabs were photographed within twenty five isolated sites with the objective of gathering a high range of color difference among the uca pugnax. The photos of the crabs were set to match the same scale of light and RGB as to not have interference from external factors such as sunlight or overcast weather. The shade of blue on the carapace provides information about the surrounding environment where the uca pugnax are found.
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Akt and Inflammatory Pathways Activation by Cache Valley Particulate Air Pollution
Sagers, Rachel; Nguyen, Andy; Weston, Jake; Grooms, Nicholas; Eggleston, Morgan; Martin, Randy; Coulombe, Roger (Utah State University)
Faculty Advisor: Coulombe, Roger (College of Agriculture and Applied Sciences; Animal, Dairy, and Veterinary Sciences Department)
The scenic mountain views of Cache Valley in Northern Utah stand in stark contrast with the valley's high concentrations of fine particulate air pollution (PM2.5), some of the worst reported in the United States. The unique geography promotes formation of ammonium nitrate (NH4NO3) from nitrogen oxides produced by motor vehicles and ammonia from dairy cow excreta. Winter atmospheric inversions, exacerbated by the mountainous terrain, trap and concentrate air pollutants. Epidemiological studies have revealed an association between PM exposure and early all-cause mortality. Exposure to PM2.5 is also associated with a variety of cardiovascular, cardiopulmonary, and neurodegenerative diseases, including myocardial infarction, stroke, COPD, lung cancer, Alzheimer's disease, and Parkinson's disease. Previous studies have shown that Cache Valley PM (CVPM) has pro-inflammatory effects, which has been linked to enhanced activation of Akt in human pulmonary epithelial cells. This research examined the cellular responses of human lung (BEAS-2B) cells exposed to CVPM and diesel exhaust particles (DEP), at 1 and 12 µg/ml concentrations of each particle type for a 24 hour exposure period. The CVPM used was collected onto stainless steel plates by a Tisch impactor. Assessment by the comet assay reveal genetic damage to CVPM exposed cells with equal potency to DEP exposed cells. Flow cytometry (p < 0.05) showed CVPM exposed cells had a significant increase in the number of actively-dividing cells compared to control cells. Whole-genome microarray identified affected genes related to inflammatory pathways, as well as activated Akt-dependent pathways. Subsequent qRT-PCR showed that CVPM exposure significantly increased expression of inflammatory markers, including IL-6, CD40LG, PLAG27, and cytochrome P450 (CYP) 1A1 (p < 0.05). Immunoblotting confirmed activation of Akt by phosphorylation of Thr308 in both CVPM and DEP exposed cells. This data supports the hypothesis that CVPM may induce pro-carcinogenic pathways with potency similar to DEP.
Faculty Advisor: Coulombe, Roger (College of Agriculture and Applied Sciences; Animal, Dairy, and Veterinary Sciences Department)
The scenic mountain views of Cache Valley in Northern Utah stand in stark contrast with the valley's high concentrations of fine particulate air pollution (PM2.5), some of the worst reported in the United States. The unique geography promotes formation of ammonium nitrate (NH4NO3) from nitrogen oxides produced by motor vehicles and ammonia from dairy cow excreta. Winter atmospheric inversions, exacerbated by the mountainous terrain, trap and concentrate air pollutants. Epidemiological studies have revealed an association between PM exposure and early all-cause mortality. Exposure to PM2.5 is also associated with a variety of cardiovascular, cardiopulmonary, and neurodegenerative diseases, including myocardial infarction, stroke, COPD, lung cancer, Alzheimer's disease, and Parkinson's disease. Previous studies have shown that Cache Valley PM (CVPM) has pro-inflammatory effects, which has been linked to enhanced activation of Akt in human pulmonary epithelial cells. This research examined the cellular responses of human lung (BEAS-2B) cells exposed to CVPM and diesel exhaust particles (DEP), at 1 and 12 µg/ml concentrations of each particle type for a 24 hour exposure period. The CVPM used was collected onto stainless steel plates by a Tisch impactor. Assessment by the comet assay reveal genetic damage to CVPM exposed cells with equal potency to DEP exposed cells. Flow cytometry (p < 0.05) showed CVPM exposed cells had a significant increase in the number of actively-dividing cells compared to control cells. Whole-genome microarray identified affected genes related to inflammatory pathways, as well as activated Akt-dependent pathways. Subsequent qRT-PCR showed that CVPM exposure significantly increased expression of inflammatory markers, including IL-6, CD40LG, PLAG27, and cytochrome P450 (CYP) 1A1 (p < 0.05). Immunoblotting confirmed activation of Akt by phosphorylation of Thr308 in both CVPM and DEP exposed cells. This data supports the hypothesis that CVPM may induce pro-carcinogenic pathways with potency similar to DEP.
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