The Potential Synergistic Effect of Saccharomyces boulardii and Lactobacillus acidophilus on Dietary Glucose Liberation

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Description
Our gut microbiome is a dynamic and complex community of microorganisms that play a vital role in our immune system and metabolism. Probiotics have gained significant traction in the health and scientific communities due to their potential health benefits particularly…

Our gut microbiome is a dynamic and complex community of microorganisms that play a vital role in our immune system and metabolism. Probiotics have gained significant traction in the health and scientific communities due to their potential health benefits particularly in our gut microbiome. A particular probiotic organism that is already known to beneficially aid in metabolism, primarily glucose metabolism is the bacteria Lactobacillus acidophilus. Due to most probiotic foods and supplements being developed using multiple strains and species, it is of interest to quantify the potential synergistic abilities of the two most used species of probiotics when used in combination: the bacteria Lactobacillus acidophilus and the yeast Saccharomyces boulardii. With the rise of metabolic disorders and the price of synthetic insulin in the United States, identifying novel approaches to regulate glucose levels could offer alternate or complementary therapies. The objective of this study was to explore any potential synergistic effects of a co-culture of S. boulardii and L. acidophilus in metabolizing dietary glucose. Probiotic supplements are typically consumed in the morning during breakfast, therefore, to replicate this process and as a source of dietary glucose, a super food mix consisting of white bread, orange juice, and one whole egg was prepared. After both probiotic organisms had been revived, they were thoroughly mixed with 1 ml of the super food mix and 1 ml of a stomach acid solution both individually and in co-culture. Total glucose levels [mg/dL] in each incubation were measured using a glucose colorimetric detection kit. In this ‘proof-of-concept' experiment, the introduction of both S.boulardii and L.acidophilus into an in vitro stomach incubation caused glucose levels to decrease by 25.6%. Although there was a marked decrease, more testing is required to determine the statistical significance. These experiments do show some promise of a positive collaborative effect between these microorganisms in reducing GI levels of glucose.
Date Created
2024-05
Agent

Biological Evaluation of Novel Rexinoids as a Therapeutic Agent for Cancer and Alzheimer's Disease

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Description
Bexarotene is a Food and Drug administration (FDA)-approved therapeutic used in the treatment of cutaneous T-cell lymphoma (CTCL). However, bexarotene therapy causes significant side effects like hyperlipidemia and hypothyroidism due to crossover activity with retinoic acid receptor (RAR), thyroid hormone…

Bexarotene is a Food and Drug administration (FDA)-approved therapeutic used in the treatment of cutaneous T-cell lymphoma (CTCL). However, bexarotene therapy causes significant side effects like hyperlipidemia and hypothyroidism due to crossover activity with retinoic acid receptor (RAR), thyroid hormone receptor (TR), and liver X receptor (LXR) signaling, respectively. More recently bexarotene has shown promise to reverse neurodegeneration, improve cognition and decrease levels of amyloid- β in transgenic mice expressing familial Alzheimer’s disease (AD) mutations. Bexarotene is a high affinity ligand for the retinoid X receptor (RXR) that heterodimerizes with the liver- X- receptors (LXR) and with peroxisome proliferator-activated receptor-gamma (PPARϒ) to control cholesterol efflux, inflammation, and transcriptionally upregulates the production of apolipoprotein (ApoE) in the brain. Enhanced ApoE expression may promote clearance of soluble Aβ peptides from the brain and reduce Aβ plaques, thus resolving both amyloid pathology and cognitive deficits. The present study assessed the potential of bexarotene and a group of 62 novel rexinoids to bind and activate RXR using a series of biological assays and screening methods, including: 1) a mammalian two-hybrid system (M2H) and an 2) Retinoid X Receptor response element (RXRE)-mediated reporter assays in cultured human cells. Moreover, Liver X Receptor response element (LXRE)-mediated luciferase assays were performed to analyze the ability of the novel analogs to activate LXRE - directed transcription, and to induce ApoE messenger ribonucleic acid (mRNA) in U87 glial cells. Furthermore, the most potent analogs were analyzed via quantitative polymerase chain reaction (qPCR) to determine efficacy in modulating expression of two critical tumor suppressor genes, activating transcription factor 3 (ATF3) and early growth response 3 (EGR3). Results from these multiple assays indicate that the panel of RXR ligands contains compounds with a range of activities, with some analogs capable of binding to RXR with higher affinity than others, and in some cases upregulating ApoE expression to a greater extent than bexarotene. The data suggests that minor modifications to the bexarotene core chemical structure may yield novel analogs possessing an equal or greater capacity to activate RXR and may be useful as therapeutic agents against CTCL and Alzheimer’s disease.
Date Created
2023
Agent

Ecological Survey of Southwest Regions Using DNA Gathered From Flies

Description

The field of forensic science has been growing and changing with improvements in DNA analysis. One field affected is forensic entomology, which is exploring many ways in which DNA can increase the application of insects in forensic science. One application…

The field of forensic science has been growing and changing with improvements in DNA analysis. One field affected is forensic entomology, which is exploring many ways in which DNA can increase the application of insects in forensic science. One application being explored is the use of insects as a source of human DNA in a criminal investigation. Using flies as a source of foreign DNA can also be utilized in ecological research to conduct surveys on the various species present in different environments. This experiment intends to determine if flies can act as a viable source of alternate DNA. This will be accomplished by an ecological survey of DNA extracted from flies. DNA extractions were performed on flies gathered from parts of the greater Phoenix area. The DNA was then amplified with primers targeting different animal species and examined to observe what animals the flies had come in contact with. Several samples had contamination due to human error and were not able to be evaluated. One DNA extraction out of fifteen yielded pig DNA, indicating flies can be used as a source of DNA. Future experiments should use different animal primers and amplify sections of DNA that can determine the different species consumed by flies. Further research into flies as a DNA source can increase the amount of information available to forensic scientists as well as improve ecologist’s observation of an environment’s biodiversity.

Date Created
2023-05
Agent

Evaluation of Novel Therapeutics for Cancer and Alzheimer's Disease

Description

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of…

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application of novel analogs of Bexarotene (RXR agonist), MeTC7 (a new potent VDR antagonist), and vitamin D as possible therapeutics for cancer and Alzheimer’s disease.

Date Created
2023-05
Agent

Enhancing Effector T Cell Migration to Mucosal Regions Using Rexinoids and Plasmid Adjuvants

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Description
Mucosal membranes represent a major site of pathogen transmission and cancer development. Enhancing T cell migration to mucosal surfaces could improve immune-based therapies for these diseases, yielding better clinical outcomes. All-trans-retinoic acid (ATRA) is a biologically active form of vitamin…

Mucosal membranes represent a major site of pathogen transmission and cancer development. Enhancing T cell migration to mucosal surfaces could improve immune-based therapies for these diseases, yielding better clinical outcomes. All-trans-retinoic acid (ATRA) is a biologically active form of vitamin A that has been shown to increase T cell migration to mucosal sites, however its therapeutic use is limited by its toxicity potential and unstable nature. ATRA-related compounds with lower toxicity and higher stability were assessed for their ability to induce similar immune migration effects as ATRA, using in vitro and in vivo model systems. Chapter 2 summarizes the first project, in which synthetic, ATRA-like compounds called rexinoids were used to modulate T cell expression of mucosal homing proteins chemokine receptor 9 (CCR9) and integrin alpha 4 beta 7 (α4β7), and alter their physical migration in vitro. Several rexinoids independently mimicked the activity of ATRA to enhance protein expression and migration, while others worked synergistically with subtoxic doses of ATRA to produce similar results. Furthermore, rexinoid administration in vivo was well-tolerated by animal models, a finding not seen with ATRA. Chapter 3 focuses on the second project, where plasmids containing ATRA-synthesizing proteins were assessed for their in vivo ability to act as mucosal vaccine adjuvants and enhance T cell migration to mucosal sites during DNA vaccination. Though increased mucosal migration was seen with use of the adjuvant plasmids, these findings were not determined to be significant. Immune-mediated protection following viral challenge was also not determined to be significant in animal models receiving both vaccine and adjuvant plasmids. The data shows that several novel rexinoids may possess enhanced clinical utility compared to ATRA, lending support for their use in immunotherapeutic approaches towards mucosal maladies. While the potential mucosal vaccine adjuvants did not show great significance in enhancing T cell migration or viral protection, further optimization of the model system may produce better results. This work helps advance knowledge of immune cell trafficking to afflicted mucosal regions. It can be used as a basis for understanding migration to other body areas, as well as for the development of better immune-based treatments.
Date Created
2022
Agent

Soil Microbial DNA Analysis of Two Relocated Sus Burials

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Description
The use of DNA testing has been focused primarily on biological samples such as blood or saliva found at crime scenes. These types of evidence in the forensic field are sometimes difficult to come by, especially when there is no…

The use of DNA testing has been focused primarily on biological samples such as blood or saliva found at crime scenes. These types of evidence in the forensic field are sometimes difficult to come by, especially when there is no body to find to verify things such as identity or status of a person. In the case of the burial of a body, they can be remote and relocated multiple times depending on each situation. Clandestine burials are not uncommon especially in the Arizona desert by the United States and Mexico border. Since there is no physical body to find the next best avenue to finding a clandestine burial is through search teams which can take weeks to months or other expensive technology such as ground penetrating radar (GPR). A new more interesting avenue to search for bodies is using the most found material–soil. Technology has allowed the possibility of using soil DNA microbiome testing initially to study the varieties of microbes that compose in soil. Microbiomes are unique and plentiful and essentially inescapable as humans are hosts of millions of them. The idea of a microbiome footprint at a crime scene seems out of reach considering the millions of species that can be found in various areas. Yet it is not impossible to get a list of varieties of species that could indicate there was a body in the soil as microbiomes seep through from decomposition. This study determines the viability of using soil microbial DNA as a method of locating clandestine graves by testing 6 different locations of a previous pig decomposition simulation. These two locations give two different scenarios that a body may be found either exposed to the sun in an open field or hidden under foliage such as a tree in the Sonoran Desert. The experiment will also determine more factors that could contribute to a correlation of microbiome specific groups associated with decomposition in soil such as firmicutes. The use of soil microbial DNA testing could open the doors to more interpretation of information to eventually be on par with the forensic use of biological DNA testing which could potentially supplement testimonies on assumed burial locations that occurs frequently in criminal cases of body relocation and reburial.
Date Created
2022-05
Agent

Assessing Silicone Wristbands as Sampling Devices by Determining Pesticide Recovery

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Description

Silicone wristbands consist of a porous surface with the potential to sequester organic contaminants in the environment. Their properties allow for them to be used as a novel sampling approach to assessing personal human exposure to environmental contaminants. The purpose…

Silicone wristbands consist of a porous surface with the potential to sequester organic contaminants in the environment. Their properties allow for them to be used as a novel sampling approach to assessing personal human exposure to environmental contaminants. The purpose of the study was to understand the effectiveness of silicone wristbands as sampling devices. This was addressed by identifying and quantifying pesticide recovery from exposed wristbands. Triplicate groups of wristbands were dosed with 37 persistent organochlorine or organophosphate pesticides and then extracted to estimate human exposure through recovery. Results suggest that silicone wristbands have the potential to absorb a number of pesticides and organic contaminants, although at varying rates and quantities. As more uptake and sequestration rates can be established, wristbands have the potential to serve as indicators of human exposure to a variety of pesticides and other chemical groups at trace amounts.

Date Created
2021-12
Agent

The Effects of Ferulic Acid Concentration on Yeast DNA Repair After Exposure to UV Radiation

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Description
Exposure of harmful ultraviolet rays (UV) is a great concern in many locations around the world, as skin diseases and cancer continue to surge. With the number of skin cancer skyrocketing past all the types of known cancers, a vast…

Exposure of harmful ultraviolet rays (UV) is a great concern in many locations around the world, as skin diseases and cancer continue to surge. With the number of skin cancer skyrocketing past all the types of known cancers, a vast majority of cases are reported daily. When the skin is exposed to UVA or UVB radiation, primarily from the sun, the UV radiation damages the DNA within the cells, which results in skin cancer. However, most damaged DNA of cells can undergo nucleotide excision repair. This involves a nuclease molecule that cuts the damaged bases. Preliminary research has developed other ways of repairing DNA damage in cells by implementing organic compounds. An organic chemical such as, ferulic acid has the ability to aid the mechanisms involved in nucleotide excision repair that takes place in your cells after DNA damage.

To test this, Saccharomyces cerevisiae was utilized. This is a primary model used in most medicinal studies due to the resemblance to human cells. This study evaluates the effect of ferulic acid, concentrations on ultraviolet radiated Rad 1 (mutant) and HB0 (wild type) yeast cells. The yeast strains were grown in two different concentrations for ferulic acid and treated with long-wave UV light under 30 seconds, 45 seconds, and 60 seconds. It is observed that, Rad 1 had heavier growth in the presence of high concentration of ferulic acid after UV treatment than HB0. But, HB0 yeast had heavier growth in the presence of lower concentrations of ferulic acid after UV treatment. Ferulic acid concentrations of 1 mM can influence cell repair after UV application by mRNA expression during nucleotide excision repair and higher absorption of UV.
Date Created
2020-12
Agent

Oral Microbiome Analysis Reveals Potential for Streamlining Diagnosis of Rheumatoid Arthritis

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Description
Rheumatoid Arthritis (RA) is an autoimmune disorder where the body mistakenly attacks healthy joints. This in turn causes inflammation resulting in pain and swelling. It is very important to get RA accurately diagnosed and treated as early as possible. Similarly,…

Rheumatoid Arthritis (RA) is an autoimmune disorder where the body mistakenly attacks healthy joints. This in turn causes inflammation resulting in pain and swelling. It is very important to get RA accurately diagnosed and treated as early as possible. Similarly, with any disease: the longer it is left untreated, the more damage it can cause. RA can cause irreversible joint damage leading to disability. The purpose of this study is to determine if oral microbiome can be used as an additional criterion to aid in diagnosing RA. Several oral microbes have already been identified as biomarkers for RA in saliva. In this study, 10 participants were recruited: 6 diagnosed with RA and 4 Healthy as a control. Two subgroups of RA were done within this study; those diagnose with a positive Rheumatoid Factor (RF) and those diagnose with a negative RF. These subgroups were then compared in order to determine the validity of using certain microbes as biomarkers for RA even when different diagnostic criteria were met. The microbe Parahaemolyticus had the largest measure of effect, showing the greatest potential for statistically significant results with a larger sample size. If we can work narrow to down specific microbes to be undoubtedly higher in abundance with already diagnosed RA patients when comparing to healthy participants, this will be a gamechanger. Not only could we give a higher sense of confidence with the diagnosis of RA, but this could streamline RA diagnosis.
Date Created
2020-12
Agent

Luminometric Analysis of Yeast Calcium Channel Homeostasis Following Hypotonic Shock

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Description
Calcium is the only ion capable of triggering electrical and chemical reactions in cells which are part of essential biomolecular processes, such as gene transcription and ion flux. Calcium homeostasis, the control of concentration levels, is therefore crucial for the…

Calcium is the only ion capable of triggering electrical and chemical reactions in cells which are part of essential biomolecular processes, such as gene transcription and ion flux. Calcium homeostasis, the control of concentration levels, is therefore crucial for the proper functioning of cells. For example, cardiomyocytes, the cells that form cardiac muscle, rely on calcium transfer process to produce muscle contraction.
The purpose of this work is to study aspects of calcium homeostasis in the model organism Saccharomyces cerevisiae, common yeast. Using luminometric techniques, the response of the yeast was monitored against a set of changes in the environment calcium abundance. The results indicate a complex response as both increase and decreases of external calcium induce elevations in cytosolic calcium concentrations.
Calcium is transferred across compartments by means of channels. In Saccharomyces cerevisiae, many of them have been identified; Cch1p-Mid1p, Vcx1p, Pmc1p, Pmr1p, and Yvc1p. Their participation in calcium homeostasis is well established. Observations of cytosolic calcium increase after a hypertonic shock are mainly associated with influx of ions from the environment though the Cch1p-Mid1p. This process is generally considered as driven by calcium concentration gradients. However, recent studies have suggested that the plasma membrane channel, Cch1p-Mid1p, may possess more sophisticated regulation and sensory mechanisms. The results of our experiments support these ideas.
We carried out experiments that subjected yeast to multiple shocks: a hypertonic shock followed by either a second hypertonic shock, a hypotonic shock, or a yeast dilution pulse where the solution volume increases by the calcium concentration has only a small change. The cytosolic calcium concentration of a yeast population was monitored via luminometry.
The main result of this study is the observation of an unexpected response to the combination of hypertonic and hypotonic shocks. In this case it was observed that the cytosolic calcium concentration increased after both shocks. This indicates that cytosolic calcium increases are not solely driven by the presence of concentration gradients. The response after the hypotonic pulse arises from more complex mechanisms that may include sensor activity at the membrane channels and the release of calcium from internal storages.
Date Created
2020-05
Agent
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