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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

Description

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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Date Created
2018-05

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

Description

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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Eat In, Not Out: A Comparative Analysis Between at Home Cooking and Restaurant Dining

Description

This creative project seeks to demonstrate the nutritional and financial benefits of cooking in versus eating out to college age students. We sought to determine what factors significantly differentiated restaurant meals versus home-cooked versions, and how we could share this

This creative project seeks to demonstrate the nutritional and financial benefits of cooking in versus eating out to college age students. We sought to determine what factors significantly differentiated restaurant meals versus home-cooked versions, and how we could share this information with our peers to potentially influence them to make a healthy lifestyle change. The first step was to determine the factors that influence college-aged students eating habits, and was presented with a review of relevant literature in several topics. We researched food literacy in young adults, the impact of fast food, social media's role in healthy eating habits, health behavior change in young adults, and the benefits of home cooking to obtain a general baseline of the knowledge of college-aged students. The initial research was utilized to write more effective blog posts that appropriately addressed our targeted demographic and to determine what platforms would be most appropriate to convey our information. These ideas were taken and then translated into a blog and Instagram account that contained healthy, copycat recipes of popular restaurant meals. We wrote 30 blog posts which were made up of 20 original recipes, 8 nutrition informational posts, and an introduction/conclusion. Finally, a focus group was hosted to ascertain the opinions of our peers, and to determine if they would be willing to make a lifestyle change in the form of cooking more frequently as opposed to eating out regularly. We provided them with a pre and post survey to gather their opinions before and after reviewing the findings of our research and project. We concluded that if given the information in an accessible way, college students are willing to eat in, not out.

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Date Created
2018-05

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

Description

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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Date Created
2019-05

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The Effects of Time Restricted Feeding on Mood

Description

Intermittent Fasting (IF) is defined as a cyclical eating pattern where an individual will fast for a specific increment of time, followed by caloric intake periods. Fasting is a crucial part of our ancestors’ adaptation to the stresses of famine

Intermittent Fasting (IF) is defined as a cyclical eating pattern where an individual will fast for a specific increment of time, followed by caloric intake periods. Fasting is a crucial part of our ancestors’ adaptation to the stresses of famine in order to maintain mental acuity and physical abilities during food deprivation. IF influences physiological changes such as: triggers protective metabolic pathways, increases metabolic flexibility and resilience, promotes DNA repair and autophagy, increases microbiome diversity and restores the natural cyclical fluctuations of the gut, increases BDNF expression in mood regulating neuronal circuits, and enhances synaptic plasticity of the brain. Research on the underlying causes of mood disorders has linked impairments in neuroplasticity and cellular resilience to this pathophysiology, which fasting could mitigate. Depression and anxiety are reported as the top impediments to academic performance. Thus, an easily implemented treatment such as intermittent fasting may be an option for combating impaired mental health in college students. This research study tested time restricted feeding (TRF) and its impact on mood states. It was hypothesized that: if college students follow a time restricted feeding pattern, then they will be less moody due to TRF’s effects on the metabolism, brain, and gut. The study consisted of 11 college students: 5 following a four-week adherence to TRF (8am-4pm eating window) and 6 in the control group. The POMS questionnaire was used to measure mood states. The participants height, weight, BMI, body fat %, and POMS scores were tested at the beginning and end of the 4 week intervention. The results were as follows: weight p=0.112 (statistical trend), BMI p=0.058 (nearly significant), body fat % p=0.114 (statistical trend), POMS p=0.014 (statistically significant). The data suggests that following a TRF eating pattern can decrease moodiness and improve mood states.

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Date Created
2019-05

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Content Analysis of Existing Nutrition Marketing Materials in Central Arizona Schools

Description

The objective of this study was to evaluate and compare the content of nutrition marketing materials within the cafeterias of schools in Central Arizona. By collecting photographs of marketing material from three elementary schools, one K-8 school, three middle schools

The objective of this study was to evaluate and compare the content of nutrition marketing materials within the cafeterias of schools in Central Arizona. By collecting photographs of marketing material from three elementary schools, one K-8 school, three middle schools and three high schools, 59 pieces of nutrition marketing were gathered. The schools chosen were a convenience sample and selected from schools that were already participating in ASU' s School Lunch Study. The photographs were sorted by grade level and then coded quantitatively and qualitatively for their purpose, visual components, strategies used and relevance. Results from this novel study provided insight into prevalence, size, textual content, educational content, strategies for fruit and vegetable marketing, messaging and overall design of existing nutrition marketing within the sample schools. This study found that the prevalence of nutrition marketing within all school cafeterias appeared to be low, particularly within elementary and middle schools. Diverse types of messaging were present among elementary, middle and high schools and a variety of appeals were utilized with little consistency. Many of the strategies used in the nutrition marketing appeared disconnected from the population it was intended to appeal to. Educational components were notably lacking within middle school cafeterias but were often effectively integrated into high school nutrition marketing. The results are unique to this population, and further research is required to evaluate the content of existing nutrition material on a larger scale, so efforts can be made to improve the persuasiveness of nutrition marketing in promoting fruit and vegetable consumption.

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Date Created
2018-12

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Examination of an Organometallic Complex on Insulin Resistance in Periadolescent Male Rats Following a 10-week High Fat Diet

Description

With the rising prevalence of obesity and diabetes, novel treatments to help mitigate or prevent symptoms of these conditions are warranted. Prior studies have shown that fossilized plant materials found in soil lowers blood sugar in a mouse model of

With the rising prevalence of obesity and diabetes, novel treatments to help mitigate or prevent symptoms of these conditions are warranted. Prior studies have shown that fossilized plant materials found in soil lowers blood sugar in a mouse model of diabetes. The goal of this study is to determine whether a similar organometallic complex (OMC) could prevent insulin resistance in the skeletal muscle brought on by chronic high fat intake by examining the protein expression of key enzymes in the insulin signaling pathway and examining glucoregulatory measures. Six-week-old periadolescent male Sprague-Dawley rats (n=42) were randomly chosen to be fed either a high fat diet (HFD) (20% protein, 20% carbohydrates [6.8% sucrose], 60% fat) or a standard chow diet (18.9% protein, 57.33% carbohydrates, 5% fat) for 10 weeks. Rats from each diet group were then randomly assigned to one of three doses of OMC (0, 0.6, 3.0 mg/mL), which was added to their drinking water and fasting blood glucose was measured at baseline and again at 10 weeks. After 10 weeks, rats were euthanized, and soleus muscle samples were isolated, snap-frozen, and stored at -80°C until analyses. Fasting plasma glucose was measured using a commercially available glucose oxidase kit. Following 6 and 10 weeks, HFD rats developed significant hyperglycemia (p<0.001 and p=0.025) compared to chow controls which was prevented by high dose OMC (p=0.021). After 10 weeks, there were significant differences in fasting serum insulin between diets (p=0.009) where levels were higher in HFD rats. No significant difference was seen in p-PI3K expression between groups. These results suggest that OMC could prevent insulin resistance by reducing hyperglycemia. Further studies are needed to characterize the effects of diet and OMC on the insulin signaling pathway in skeletal muscle, the main site of postprandial glucose disposal. This study was supported by a grant from Isagenix International LLC as well as funds from Barrett, the Honors College at Arizona State University, Tempe Campus.

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Date Created
2018-12

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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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Date Created
2018-12

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Incorporating Nutritional Support as Complementary Therapy for Cancer Patients Undergoing Chemotherapy Treatment

Description

Nutritional support offered before and during chemotherapy treatment is proven to improve the outcomes of treatment (Bernhardson, 2016). This project seeks to examine current forms of nutritional support offered to patients, as well as the models of care and support

Nutritional support offered before and during chemotherapy treatment is proven to improve the outcomes of treatment (Bernhardson, 2016). This project seeks to examine current forms of nutritional support offered to patients, as well as the models of care and support teams in cancer treatment centers. The basis for this project incorporated personal experiences at M.D. Anderson Cancer Center in Gilbert, Arizona as well as research into the work of clinical oncology dietitians. An intense interest in food videos and blogs also informed this project, and was incorporated in the hope of providing chemotherapy patients a platform to discover recipes specific to their unique situation. The combination of this research was utilized to create several videos which demonstrated specific recipes beneficial for patients as well as creating a platform for this particular population. While nutritional support can take multiple forms, the focus of nutritional support surrounds symptom management. The common side effects of chemotherapy such as nausea, mucositis (mouth sores), and extreme weight loss were taken into account. Recipes were formulated to directly address these conditions and each recipe was broken down into the benefits of both macronutrients and micronutrients. In addition to formulating specific recipes and videos, barriers to proper nutritional support were examined and explained. These barriers include understaffing of clinical dietitians at cancer treatment centers, a patient's lack of transportation to and from treatments, as well as an overwhelming viewpoint that nutritional support is only required for extreme cases of malnutrition. Combatting these barriers and offering more forms of nutritional support will help to increase a patient's positive response to treatment, manage their symptoms, and improve their overall quality of life.

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Date Created
2018-12