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Effect of Rexinoids on Inducing Effector T Cell Chemotaxis

Description

The retinoid-X receptor (RXR) can form heterodimers with both the retinoic-acid
receptor (RAR) and vitamin D receptor (VDR). The RXR/RAR dimer is activated by ligand all
trans retinoic acid (ATRA), which culminates in gut-specific effector T cell migration. Similarly,

The retinoid-X receptor (RXR) can form heterodimers with both the retinoic-acid
receptor (RAR) and vitamin D receptor (VDR). The RXR/RAR dimer is activated by ligand all
trans retinoic acid (ATRA), which culminates in gut-specific effector T cell migration. Similarly,
the VDR/RXR dimer binds 1,25(OH)2D3 to cause skin-specific effector T cell migration.
Targeted migration is a potent addition to current vaccines, as it would induce activated T cell
trafficking to appropriate areas of the immune system and ensure optimal stimulation (40).
ATRA, while in use clinically, is limited by toxicity and chemical instability. Rexinoids
are stable, synthetically developed ligands specific for the RXR. We have previously shown that
select rexinoids can enhance upregulation of gut tropic CCR9 receptors on effector T cells.
However, it is important to establish whether these cells can actually migrate, to show the
potential of rexinoids as vaccine adjuvants that can cause gut specific T cell migration.
Additionally, since the RXR is a major contributor to VDR-mediated transcription and
epidermotropism (15), it is worth investigating whether these compounds can also function as
adjuvants that promote migration by increasing expression of skin tropic CCR10 receptors on T
cells.
Prior experiments have demonstrated that select rexinoids can induce gut tropic migration
of CD8+ T cells in an in vitro assay and are comparable in effectiveness to ATRA (7). The effect
of rexinoids on CD4+ T cells is unknown however, so the aim of this project was to determine if
rexinoids can cause gut tropic migration in CD4+ T cells to a similar extent. A secondary aim
was to investigate whether varying concentrations in 1,25-Dihydroxyvitamin D3 can be linked to
increasing CCR10 upregulation on Jurkat CD4+ T cells, with the future aim to combine 1,25
Dihydroxyvitamin D3 with rexinoids.
These hypotheses were tested using murine splenocytes for the migration experiment, and
human Jurkat CD4+ T cells for the vitamin D experiment. Migration was assessed using a
Transwell chemotaxis assay. Our findings support the potential of rexinoids as compounds
capable of causing gut-tropic migration in murine CD4+ T cells in vitro, like ATRA. We did not
observe conclusive evidence that vitamin D3 causes upregulated CCR10 expression, but this
experiment must be repeated with a human primary T cell line.

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2020-05

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A Review of the Human Vermiform Appendix and its Proposed Function

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Since its discovery in 1524, many people have characterized the vermiform appendix. Charles Darwin considered the human appendix to be a vestige and a useless structure. Others at the time opposed this hypothesis. However, Darwin's hypothesis became prevalent one until

Since its discovery in 1524, many people have characterized the vermiform appendix. Charles Darwin considered the human appendix to be a vestige and a useless structure. Others at the time opposed this hypothesis. However, Darwin's hypothesis became prevalent one until recently when there became a renewed interest in the appendix because of advancements in microscopes, knowledge of the immune system, and phylogenetics. In this review, I will argue that the vermiform appendix, although still not completely understood, has important functions. First, I will give the anatomy of the appendix. I will discuss the comparative anatomy between different animals and also primates. I will address the effects of appendicitis and appendectomy. I will give background on vestigial structures and will discuss if the appendix is a vestige. Following, I will review the evolution of the appendix. Finally, I will argue that the function of the appendix is as an immune organ, including discussion of gut-associated lymphoid tissue (GALT), development of lymphoid follicles in GALT and their comparison within different organs, Immunoglobulin A (IgA) function in the gut, biofilms as evidence that the appendix is a safe-house for beneficial bacteria, re-inoculation of the bowel, and protection against recurring infection. I will conclude with future studies that should be conducted to further our understanding of the vermiform appendix.

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2018-05

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The Development of a Plant-Expressed M2e-Based Universal Influenza Vaccine

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Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix

Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix 2 protein (M2e) of influenza A, however, has demonstrated high levels of conservation. On its own it is poorly immunogenic and offers little protection against influenza infections, but by combining it with a potent adjuvant, this limitation may be overcome. Recombinant immune complexes, or antigens fused to antibodies that have been engineered to form incredibly immunogenic complexes with one another, were previously shown to be useful, immunogenic platforms for the presentation of various antigens and could provide the boost in immunogenicity that M2e needs to become a powerful universal influenza A vaccine. In this thesis, genetic constructs containing geminiviral replication proteins and coding for a consensus sequence of dimeric M2e fused to antibodies featuring complimentary epitopes and epitope tags were generated and used to transform Agrobacterium tumefaciens. The transformed bacteria was then used to cause Nicotiana benthamiana to transiently express M2e-RICs at very high levels, with enough RICs being gathered to evaluate their potency in future mouse trials. Future directions and areas for further research are discussed.

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2018-05

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Development of Nanozymes from 2D Materials for Optical Detection of Neurotransmitters

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This paper discusses the possibility of utilizing 2D molybdenum disulfide (MoS2) as a nanozyme to detect dopamine colorimetric assays, first by detecting color change in liquid solutions due to oxidation and then second on paper-based assays. MoS2 samples dispersed in

This paper discusses the possibility of utilizing 2D molybdenum disulfide (MoS2) as a nanozyme to detect dopamine colorimetric assays, first by detecting color change in liquid solutions due to oxidation and then second on paper-based assays. MoS2 samples dispersed in methylcellulose (MC) solution were prepared using liquid-phase exfoliation through sonication. The dopamine (DOPA) and hydrogen peroxide (H¬¬2O2) solutions were prepared separately in specific concentrations. The solutions were mixed in a well plate and colorimetric results were analyzed by a plate reader, revealing a quantitative relationship between dopamine concentration and absorbance. Subsequent testing was conducted using paper assays, where combined solutions of DOPA and H2O2 were dropped onto paper with printed wax wells that contained dried MoS2. An analysis of the color change was conducted using a smartphone application called Color Grab to detect the red, green, and blue (RGB) values. Plotting the RGB results across the dopamine concentrations revealed a positively correlated relationship between the two factors, suggesting that a predictive model could be developed to predict dopamine concentrations based on measured colorimetric values.

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2019-05

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Burkina Faso Hospital Microgrid Case Study

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This paper analyzes Burkina Faso’s Souro Sanou University Hospital Center’s energy needs and discusses whether or not solar panels are a good investment. This paper also discusses a way to limit the damage caused by power outages. The hospital has

This paper analyzes Burkina Faso’s Souro Sanou University Hospital Center’s energy needs and discusses whether or not solar panels are a good investment. This paper also discusses a way to limit the damage caused by power outages. The hospital has a history of problems with power outages; in the summer they have power outages every other day lasting between one to four hours, and in the rainy season they have outages once every other week lasting the same amount of time.
The first step in this analysis was collecting relevant data which includes: location, electricity rates, energy consumption, and existing assets. The data was entered into a program called HOMER. HOMER is a program which analyzes an electrical system and determines the best configuration and usage of assets to get the lowest levelized cost of energy (LCOE). In HOMER, five different analyses were performed. They reviewed the hospital’s energy usage over 25 years: the current situation, one of the current situation with added solar panels, and another where the solar panels have single axis tracking. The other two analyses created incentives to have more solar panels, one situation with net metering, and one with a sellback rate of 0.03 $/kWh. The result of the analysis concluded that the ideal situation would have solar panels with a capacity of 300 kW, and the LCOE in this situation will be 0.153 $/kWh. The analysis shows that investing in solar panels will save the hospital approximately $65,500 per year, but the initial investment of $910,000 only allows for a total savings of $61,253 over the life of the project. The analysis also shows that if the electricity company, Sonabel, eventually buys back electricity then net metering would be more profitable than reselling electricity for the hospital.
Solar panels will help the hospital save money over time, but they will not stop power outages from happening at the hospital. For the outages to stop affecting the hospital’s operations they will have to invest in an uninterrupted power supply (UPS). The UPS will power the hospital for the time between when the power goes out and when their generators are turning on which makes it an essential investment. This will stop outages from affecting the hospital, and if the power goes out during the day then the solar panels can help supplement the energy production which will take some of the strain from their generators.
The results of this study will be sent to officials at the hospital and they can decide if the large initial investment justifies the savings. If the solar panels and UPS can save one life, then maybe the large initial investment is worth it.

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2019-05

Algal Fuels: A Future Less Green than the Plant

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The algal fuel industry has existed since the 1980s without fully commercializing a product. Algal fuels are potentially viable replacements for fossil fuels due to their fast cultivation, high oil content, carbon dioxide sequestration during growth, and ability to

The algal fuel industry has existed since the 1980s without fully commercializing a product. Algal fuels are potentially viable replacements for fossil fuels due to their fast cultivation, high oil content, carbon dioxide sequestration during growth, and ability to be grown on non-arable land. For this thesis, six companies from 61 investigated were interviewed about their history with biofuels, technological changes they have gone through, and views for the future of the industry. All companies interviewed have moved away from fuel production largely due to high production costs and have moved primarily toward pharmaceuticals and animal feed production as well as wastewater treatment. While most do not plan to return to the biofuel industry in the near future, a return would likely require additional legislation, increased technological innovation, and coproduction of multiple products.

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2019-05

The Perception of Genetic Risk: What Do We Know About Biological and Psychological Diseases and Where Did We Learn It

Description

As a biology major, many of my classes have included studying the fundamentals of genetics or investigating the way genetics influence heritability of certain diseases. When I began taking upper-division psychology courses, the genetic factors of psychological disorders became an

As a biology major, many of my classes have included studying the fundamentals of genetics or investigating the way genetics influence heritability of certain diseases. When I began taking upper-division psychology courses, the genetic factors of psychological disorders became an important part of the material. I was exposed to a new idea: that genes were equally important in studying somatic diseases as they were to psychological disorders. As important as genetics are to psychology, they are not part of the required courses for the major; I found many of my peers in psychology courses did not have a grasp on genetic fundamentals in the same way biology majors did. This was a disconnect that I also found in my own life outside the classroom. Growing up, my mother consistently reminded me to limit my carbs and watch my sugars. Diabetes was very prevalent in my family and I was also at risk. I was repeatedly reminded of my own genes and the risk I faced in having this biological disorder. However, my friend whose father was an alcoholic did not warn her in the same way. While she did know of her father's history, she was not warned of the potential for her to become an alcoholic. While my behavior was altered due to my mother's warning and my own knowledge of the genetic risk of diabetes, I wondered if other people at genetic risk of psychological disorders also altered their behavior. Through my thesis, I hope to answer if students have the same perceived genetic knowledge of psychological diseases as they do for biological ones. In my experience, it is not as well known that psychological disorders have genetic factors. For example, alcohol is commonly used by college students. Alcohol use disorder is present in 16.2% of college aged students and "40-60% of the variance of risk explained by genetic influences." (DSM V, 2013) Compare this to diabetes that has "several common genetic variants that account for about 10% of the total genetic effects," but is much more openly discussed even though it is less genetically linked. (McVay, 2015)This stems from the stigma/taboo surrounding many psychological disorders. If students do know that psychological disorder are genetically influenced, I expect their knowledge to be skewed or inaccurate. As part of a survey, I hope to see how strong they believe the genetic risk of certain diseases are as well as where they gained this knowledge. I hypothesize that only students with a background in psychology will be able to correctly assign the genetic risk of the four presented diseases. Completing this thesis will require in-depth study of the genetic factors, an understanding of the way each disease is perceived and understood by the general population, and a statistical analysis of the survey responses. If the survey data turns out as I expect where students do not have a strong grasp of diseases that could potentially influence their own health, I hope to find a way to educate students on biological and psychological diseases, their genetic risk, and how to speak openly about them.

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2018-05

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Worker Policing Mechanisms in Ponerine Ant Species

Description

For colonies of ponerine ant species, sterility regulation after a founding queen's death is not totally achieved in the worker caste, and the possibility of sexual reproduction is opened to workers. The persisting survival of these colonies is dependent on

For colonies of ponerine ant species, sterility regulation after a founding queen's death is not totally achieved in the worker caste, and the possibility of sexual reproduction is opened to workers. The persisting survival of these colonies is dependent on capturing the optimal reproductive ratio; yet, an informational gap bounds the mechanisms detailing the selection of new reproductives and the suppression of ovarian development in rejected reproductives. We investigated the mechanisms of worker policing, one of the primary methods of ovarian suppression, through continuous video observation for a period of five days at the start of colony instability. Observations suggest policing in H. saltator is performed by a majority of a colony, including potential reproductives, and requires multiple events to fully discourage ovarian growth.

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2018-12

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Social-Life Cycle Assessment: Oil Extraction in Section 1002 of the National Arctic Wildlife Refuge

Description

Drilling in Section 1002 has been an ongoing debate since the region was designated as a potential area for drilling projects, pending congressional approval in 1980. In 2017, the area was officially opened up for oil and gas development through

Drilling in Section 1002 has been an ongoing debate since the region was designated as a potential area for drilling projects, pending congressional approval in 1980. In 2017, the area was officially opened up for oil and gas development through its passage in the GOP Tax Cuts and Jobs Act of 2017. This act requires 2 lease sales of 400,000 acres, with an allowed 2,000 acre physical footprint (not including pipelines, ice roads, or gravel mines). Using Social-Life Cycle Assessment methodology to assess the process of oil extraction in Section 1002, significant benefits and drawbacks of drilling in this region, with economic, cultural, and social impacts ranging from the local level to the state level to the national level were identified.

Stakeholders impacted by oil development in the Section 1002 region include the Kaktovik community who lives within the Program Area, the Gwich’in people who live south of ANWR, the corporations who will be leasing the land, as well as the employees who will be working on the projects. These stakeholders share similar values and interests, however, when it comes down to the attainment of these values, there are significant differences in opinion. This debate comes down specifically to the desire to ensure stability for one’s family and community, as this means 2 different things to the majority stakeholders on this issue: The Inupiaq and the Gwich’in. The Inupiaq ,who live in Kaktovik specifically ,are particularly keen on the idea of drilling in the Section 1002 region, because the revenues and opportunities that come with the oil and gas development provide access to better standards of living and a more westernized way of life. The Gwich’in, however, value their relationship to the land and the caribou that are at risk of significant change. These 2 groups are critical to the debate, but the state and federal governments have the final say, and a financial incentive to move forward with the lease sales.

Utilizing the S-LCA framework, life cycle impacts of drilling on society are found using indicators that are identified and assessed using both qualitative and quantitative means. Although some conclusions are uncertain due to the forward-looking nature of this S-LCA, the Increasing/Decreasing trends can be identified and confidently attributed to the specific indicators.

Significant Results:
Significant issues this study has highlighted include the resulting impacts, both positive and negative, on the communities affected by oil and gas development in Section 1002. Significant stakeholders include the Kaktovik community, the Gwich’in people, the oil and gas workers in the state of Alaska, and the oil and gas companies themselves. The local residents are the most affected by the impacts of development, with significant issues pertaining to potential for significant lifestyle change, the increased risk of impact on subsistence species, the risks associated with pollution, and the effect on the economy through revenues and job availability.

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2019-05

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A protocol for Resolving Indeterminate Blood Phenotypes in Rhesus (Macaca mulatta) and Cynomolgus Macaques (M. fascicularis)

Description

Rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques are the most commonly used nonhuman primate models in biomedical research. It is therefore critical to correctly infer each study animal's ABO blood group phenotype to prevent fatal transfusion- and transplantation-induced immune

Rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques are the most commonly used nonhuman primate models in biomedical research. It is therefore critical to correctly infer each study animal's ABO blood group phenotype to prevent fatal transfusion- and transplantation-induced immune responses. While most macaques can be efficiently and accurately phenotyped using a DNA-based assay, we have identified some animals that are unable to be classified as type A, B, or AB and therefore exhibit an indeterminate phenotype. The purpose of this study was to develop a protocol for resolving indeterminate blood group phenotypes and consequently determine if these animals do indeed belong to an O blood phenotype. We attempted both direct and cloning-based sequencing of 21 animals phenotyped as A, B, AB, or indeterminate in order to assess variation at the functional mutation site in exon 7 of the macaque ABO gene. Although direct-from-PCR Sanger sequencing was unable to generate reliable sequence results, our cloned plasmid protocol yielded high quality sequences consistent with known blood group-specific alleles and as such can be used to identify informative polymorphisms at this locus.

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2018-05