Matching Items (553)

Filtering by

Clear all filters

131368-Thumbnail Image.png

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.

Contributors

Agent

Created

Date Created
2020-05

133795-Thumbnail Image.png

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.

Contributors

Agent

Created

Date Created
2018-05

133844-Thumbnail Image.png

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.

Contributors

Agent

Created

Date Created
2018-05

133847-Thumbnail Image.png

Structure-function study of N-isopropylacrylamide copolymers with enzyme degradable GAPGLF and GAPGLL side chains

Description

With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending

With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending on the conditions in which polymers are used, they are modified to accommodate a specific need. For instance, polymers used in drug delivery are more efficient if they are biodegradable. This ensures that the delivery system does not remain in the body after releasing the drug. It is therefore crucial that the polymer used in the drug system possess biodegradable properties. Such modification can be done in different ways including the use of peptides to make copolymers that will degrade in the presence of enzymes. In this work, we studied the effect of a polypeptide GAPGLL on the polymer NIPAAm and compare with the previously studied Poly(NIPAAm-co-GAPGLF). Both copolymers Poly(NIPAAm-co-GAPGLL) were first synthesized from Poly(NIPAAm-co-NASI) through nucleophilic substitution by the two peptides. The synthesis of these copolymers was confirmed by 1H NMR spectra and through cloud point measurement, the corresponding LCST was determined. Both copolymers were degraded by collagenase enzyme at 25 ° C and their 1H NMR spectra confirmed this process. Both copolymers were cleaved by collagenase, leading to an increase in solubility which yielded a higher LCST compared to before enzyme degradation. Future studies will focus on evaluating other peptides and also using other techniques such as Differential Scanning Microcalorimetry (DSC) to better observe the LCST behavior. Moreover, enzyme kinetics studies is also crucial to evaluate how fast the enzyme degrades each of the copolymers.

Contributors

Agent

Created

Date Created
2018-05

132569-Thumbnail Image.png

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.

Contributors

Agent

Created

Date Created
2019-05

133208-Thumbnail Image.png

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.

Contributors

Agent

Created

Date Created
2018-12

133469-Thumbnail Image.png

Dynamic Changes in Heart Rate and Cerebral Blood Flow During Acute Vagal Nerve Stimulation

Description

Vagal Nerve Stimulation (VNS) has been shown to be a promising therapeutic technique in treating many neurological diseases, including epilepsy, stroke, traumatic brain injury, and migraine headache. The mechanisms by which VNS acts, however, are not fully understood but may

Vagal Nerve Stimulation (VNS) has been shown to be a promising therapeutic technique in treating many neurological diseases, including epilepsy, stroke, traumatic brain injury, and migraine headache. The mechanisms by which VNS acts, however, are not fully understood but may involve changes in cerebral blood flow. The vagus nerve plays a significant role in the regulation of heart rate and cerebral blood flow that are altered during VNS. Here, we examined the effects of acute vagal nerve stimulation on both heart rate and cerebral blood flow. Laser Speckle Contrast Analysis (LASCA) was used to analyze the cerebral blood flow of male Long\u2014Evans rats. Results showed two distinct patterns of responses whereby animals either experienced a mild or severe decrease in heart rate during VNS. Further, animals that displayed mild heart rate decreases showed an increase in cerebral blood flow that persisted beyond VNS. Animals that displayed severe decreases showed a transient decrease in cerebral blood flow followed by an increase that was greater than that observed in mild animals but progressively decreased after VNS. The results suggest two distinct patterns of changes in both heart rate and cerebral blood flow that may be related to the intensity of VNS.

Contributors

Agent

Created

Date Created
2018-05

133485-Thumbnail Image.png

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.

Contributors

Agent

Created

Date Created
2018-05

133517-Thumbnail Image.png

Image Analysis for Registration, Segmentation, and Intensity Measurement of 2-Photon Microscope Images using MATLAB

Description

Traumatic brain injury (TBI) is a major concern in public health due to its prevalence and effect. Every year, about 1.7 million TBIs are reported [7]. According to the According to the Centers for Disease Control and Prevention (CDC), 5.5%

Traumatic brain injury (TBI) is a major concern in public health due to its prevalence and effect. Every year, about 1.7 million TBIs are reported [7]. According to the According to the Centers for Disease Control and Prevention (CDC), 5.5% of all emergency department visits, hospitalizations, and deaths from 2002 to 2006 are due to TBI [8]. The brain's natural defense, the Blood Brain Barrier (BBB), prevents the entry of most substances into the brain through the blood stream, including medicines administered to treat TBI [11]. TBI may cause the breakdown of the BBB, and may result in increased permeability, providing an opportunity for NPs to enter the brain [3,4]. Dr. Stabenfeldt's lab has previously established that intravenously injected nanoparticles (NP) will accumulate near the injury site after focal brain injury [4]. The current project focuses on confirmation of the accumulation or extravasation of NPs after brain injury using 2-photon microscopy. Specifically, the project used controlled cortical impact injury induced mice models that were intravenously injected with 40nm NPs post-injury. The MATLAB code seeks to analyze the brain images through registration, segmentation, and intensity measurement and evaluate if fluorescent NPs will accumulate in the extravascular tissue of injured mice models. The code was developed with 2D bicubic interpolation, subpixel image registration, drawn dimension segmentation and fixed dimension segmentation, and dynamic image analysis. A statistical difference was found between the extravascular tissue of injured and uninjured mouse models. This statistical difference proves that the NPs do extravasate through the permeable cranial blood vessels in injured cranial tissue.

Contributors

Agent

Created

Date Created
2018-05

133535-Thumbnail Image.png

Optical Feedback Mechanism for Detecting Cerebrospinal Fluid Leaks During Spinal Surgery

Description

For my honors thesis, I developed a proof of concept alpha prototype of a biomedical device for detection of cerebrospinal fluid leaks during spinal surgery. Cerebrospinal fluid leaks are a consequence of tears in the dura mater of the spinal

For my honors thesis, I developed a proof of concept alpha prototype of a biomedical device for detection of cerebrospinal fluid leaks during spinal surgery. Cerebrospinal fluid leaks are a consequence of tears in the dura mater of the spinal cord and can result in potentially life-threatening conditions and are overall a large burden not only on the patient but upon the clinical teams managing the patient postoperatively. What I created was an optical sensor that I programmed to be sensitive to detecting green wavelength light. The device would ideally be attached to surgical drain tubing and used in conjunction with fluorescein (a green fluorescent dye) infused lumbar punctures into the spinal canal of patients. As the dye circulates through the spinal cord, any tears in the dura mater would cause the fluorescein to leak out with cerebrospinal fluid into the incision site. This fluid may then be collected by the surgical drain where the sensor may detect the fluorescein, triggering a buzzer response that would notify the patient or the surgeons of an ongoing leak that requires repair. The time I spent on my thesis involved sensor validation to ensure it could differentiate between colors, testing the sensor's color sensitivity by performing a fluorescein aliquot, and running proof of concept testing that could show the sensor can detect fluorescein drain tubing and provide an adequate response. The sensor was able to differentiate between varying concentrations of fluorescein in solution and provided exceptional results in its proof-of-concept testing. Next steps will be to re-run the sensor validation study with different dyes as well as consolidating the device's electrical hardware onto a single circuit board as development of beta and gamma prototypes move forward.

Contributors

Agent

Created

Date Created
2018-05