Matching Items (351)

134374-Thumbnail Image.png

Analysis of the prrAB two-component system regulatory effects on the lipid profile of Mycobacterium smegmatis

Description

The prrAB two-component system has been shown to be essential for viability in Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. To study this system, several prrAB mutants of Mycobacterium

The prrAB two-component system has been shown to be essential for viability in Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. To study this system, several prrAB mutants of Mycobacterium smegmatis, a close relative of Mtb, were created for study. These mutants included a deletion mutant complemented with prrA from Mtb controlled by Pmyc1_tetO, a deletion mutant, and a deletion mutant complemented with prrAB from M. smegmatis controlled by the native prrAB promoter sequence (~167 bp upstream sequence of prrAB). In a previous study, the prrAB deletion mutant clumped excessively relative to the wild-type strain when cultured in a nitrogen-limited medium. To address this irregularity, the lipid profiles of these mutants were analyzed through several experimental methods. Untargeted lipidomic profiles were analyzed by Electrospray Ionization Mass Spectrometry (ESI-MS). The ESI-MS data suggested the deletion mutant accumulates triacylglycerol species relative to the wild-type strain. This data was verified by thin-layer chromatography (TLC) and densitometry of the TLC images. The mycolic acid profile of each mutant was also analyzed by TLC but no noteworthy differences were found. High-throughput RNA-Seq analysis revealed several genes involved in lipid biosynthetic pathways upregulated in the prrAB deletion mutant, thus corroborating the ESI-MS and TLC data.

Contributors

Agent

Created

Date Created
  • 2017-05

135681-Thumbnail Image.png

The Neurochemical Consequences of Music Therapy on Dementia Patients

Description

As the incidence of dementia continues to rise, the need for an effective and non-invasive method of intervention has become increasingly imperative. Music therapy has exhibited these qualities in addition

As the incidence of dementia continues to rise, the need for an effective and non-invasive method of intervention has become increasingly imperative. Music therapy has exhibited these qualities in addition to relatively low implementation costs, therefore establishing itself as a promising means of therapeutic intervention. In this review, current research was investigated in order to determine its effectiveness and uncover the neurochemical mechanisms that lead to positive manifestations such as improved memory recall, increased social affiliation, increased motivation, and decreased anxiety. Music therapy has been found to improve several aspects of memory recall. One proposed mechanism involves temporal entrainment, during which the melodic structures present in music provide a framework for chunking information. Although entrainment's role in the treatment of motor defects has been thoroughly studied, its role in treating cognitive disorders is still relatively new. Musicians have also been shown to demonstrate extensive plastic changes; therefore, it is hypothesized that non-musicians may also glean some benefits from engaging in music. Social affiliation has been found to increase due to increases in endogenous oxytocin. Oxytocin has also been shown to strengthen hippocampal spike transmission, a promising outcome for Alzheimer's patients. An increase in motivation has also been found to occur due to music's ability to tap into the reward center of the brain. Dopaminergic transmission between the VTA, NAc and higher functioning regions such as the OFC and hypothalamus has been revealed. Additionally, relaxing music decreases stress levels and modifies associated autonomic processes, i.e. heart rate, blood pressure, and respiratory rate. On the contrary, stimulating music has been found to initiate sympathetic nervous system activity. This is thought to occur by either a reflexive brainstem response or stimulus interpretation by the amygdala.

Contributors

Agent

Created

Date Created
  • 2016-05

135814-Thumbnail Image.png

Exploration of Enzymatic Efficiency in Double-Stranded DNA by Uracil-DNA Glycosylase and Optimization of Glycosylation Reaction of DNA Precursor

Description

The two chapters of this thesis focus on different aspects of DNA and the properties of nucleic acids as the whole. Chapter 1 focuses on the structure of DNA and

The two chapters of this thesis focus on different aspects of DNA and the properties of nucleic acids as the whole. Chapter 1 focuses on the structure of DNA and its relationship to enzymatic efficiency. Chapter 2 centers itself on threose nucleic acid and optimization of a step in the path to its synthesis. While Chapter 1 discusses DNA and Uracil-DNA Glycosylase with regards to the base excision repair pathway, Chapter 2 focuses on chemical synthesis of an intermediate in the pathway to the synthesis of TNA, an analogous structure with a different saccharide in the sugar-phosphate backbone.
Chapter 1 covers the research under Dr. Levitus. Four oligonucleotides were reacted for zero, five, and thirty minutes with uracil-DNA glycosylase and subsequent addition of piperidine. These oligonucleotides were chosen based on their torsional rigidities as predicted by past research and predictions. The objective was to better understand the relationship between the sequence of DNA surrounding the incorrect base and the enzyme’s ability to remove said base in order to prepare the DNA for the next step of the base excision repair pathway. The first pair of oligonucleotides showed no statistically significant difference in enzymatic efficiency with p values of 0.24 and 0.42, while the second pair had a p value of 0.01 at the five-minute reaction. The second pair is currently being researched at different reaction times to determine at what point the enzyme seems to equilibrate and react semi-equally with all sequences of DNA.
Chapter 2 covers the research conducted under Dr. Chaput. Along the TNA synthesis pathway, the nitrogenous base must be added to the threofuranose sugar. The objective was to optimize the original protocol of Vorbrüggen glycosylation and determine if there were better conditions for the synthesis of the preferred regioisomer. This research showed that toluene and ortho-xylene were more preferable as solvents than the original anhydrous acetonitrile, as the amount of preferred isomer product far outweighed the amount of side product formed, as well as improving total yield overall. The anhydrous acetonitrile reaction had a final yield of 60.61% while the ortho-xylene system had a final yield of 94.66%, an increase of approximately 32%. The crude ratio of preferred isomer to side product was also improved, as it went from 18% undesired in anhydrous acetonitrile to 4% undesired in ortho-xylene, both values normalized to the preferred regioisomer.

Contributors

Agent

Created

Date Created
  • 2016-05

135829-Thumbnail Image.png

Environmental Impacts on Light Stable Isotope Systems

Description

Isotopic analyses of archaeological and modern materials are commonly used to reconstruct diet, climate, and habitat. This study analyzes 15 camelid samples from three sites (two archaeological, one modern) in

Isotopic analyses of archaeological and modern materials are commonly used to reconstruct diet, climate, and habitat. This study analyzes 15 camelid samples from three sites (two archaeological, one modern) in South America to determine their carbon and nitrogen isotopic values to further explore the relationship between stable isotopes and environments. Camelid individuals in the modern site of Cuenca, Ecuador had a diet of almost entirely C3 vegetation, while those in Chen Chen, Peru had slightly higher values, still consistent with C3 plants. Those in the higher altitude site of Pumapunku, Bolivia had higher δ13C values than expected, indicating they may have been foddered with a mixed diet. These isotopic data indicate that vegetation, and therefore herbivore diets, are influenced by altitude. Additionally, it was found that a positive linear relationship exists between δ15N values and aridity of a site. Results indicate that aspects of the environment such as aridity are reflected in isotopic signatures. These results contribute to the increasing amount of data on isotopic variation in South American camelids, both modern and archaeological.

Contributors

Agent

Created

Date Created
  • 2016-05

135960-Thumbnail Image.png

Expression of Pleiotrophin as Separate Domains to Examine Glycosaminoglycan Binding Sites

Description

Glycosaminoglycan (GAG) binding by the cytokine pleiotrophin (PTN) was examined by expressing both thrombospondin 1 type-1 repeat domains of PTN separately, as PTN-N and PTN-C. PTN-N contains residues 31-89, and

Glycosaminoglycan (GAG) binding by the cytokine pleiotrophin (PTN) was examined by expressing both thrombospondin 1 type-1 repeat domains of PTN separately, as PTN-N and PTN-C. PTN-N contains residues 31-89, and PTN-C contains residues 90-146. Nuclear magnetic resonance (NMR) experiments were conducted on both PTN-N and PTN-C to elucidate GAG binding regions. Titration with heparin dp6 showed a twofold increase in affinity when expressing PTN-N and PTN-C separately rather than as intact PTN. Paramagnetic relaxation rate enhancement experiments and surface paramagnetic relaxation enhancement (PRE) perturbation experiments were used to determine which residues were involved in GAG binding. One binding site was observed in PTN-N, around residue T82, and two binding sites were observed in PTN-C, one around residue K93 and the other around residue G142. These observed binding sites agree with the binding sites already proposed by the Wang lab group and other studies. Future work on the subject could be done on confirming that other varieties and length GAGs bind at the same sites, as well as examining the effect longer GAG fragments have on the affinity of intact PTN versus separate domains.

Contributors

Agent

Created

Date Created
  • 2015-12

135762-Thumbnail Image.png

Use of the Multiple Myeloma Immunosignature for the Synthesis of Synbody Therapeutic Treatment

Description

Currently, treatment for multiple myeloma (MM), a hematological cancer, is limited to post-symptomatic chemotherapy combined with other pharmaceuticals and steroids. Even so, the immuno-depressing cancer can continue to proliferate, leading

Currently, treatment for multiple myeloma (MM), a hematological cancer, is limited to post-symptomatic chemotherapy combined with other pharmaceuticals and steroids. Even so, the immuno-depressing cancer can continue to proliferate, leading to a median survival period of two to five years. B cells in the bone marrow are responsible for generating antigen-specific antibodies, but in MM the B cells express mutated, non-specific monoclonal antibodies. Therefore, it is hypothesized that antibody-based assay and therapy may be feasible for detecting and treating the disease. In this project, 330k peptide microarrays were used to ascertain the binding affinity of sera antibodies for MM patients with random sequence peptides; these results were then contrasted with normal donor assays to determine the "immunosignatures" for MM. From this data, high-binding peptides with target-specificity (high fluorescent intensity for one patient, low in all other patients and normal donors) were selected for two MM patients. These peptides were narrowed down to two lists of five (10 total peptides) to analyze in a synthetic antibody study. The rationale behind this originates from the idea that antibodies present specific binding sites on either of their branches, thus relating high binding peptides from the arrays to potential binding targets of the monoclonal antibodies. Furthermore, these peptides may be synthesized on a synthetic antibody scaffold with the potential to induce targeted delivery of radioactive or chemotherapeutic molecular tags to only myelomic B cells. If successful, this would provide a novel alternative to current treatments that is less invasive, has fewer side effects, more specifically targets the cause of MM, and reliably diagnoses the cancer in the presymptomatic stage.

Contributors

Agent

Created

Date Created
  • 2016-05

135903-Thumbnail Image.png

Factors Associated with Second Generation Cambodian American Young Adults' Mental and Behavioral Health

Description

The purpose of the study was to examine the associations of protective (ethic identity, parent-child closeness) and risk (perceived discrimination, parent-child role reversal) factors with mental and behavioral health in

The purpose of the study was to examine the associations of protective (ethic identity, parent-child closeness) and risk (perceived discrimination, parent-child role reversal) factors with mental and behavioral health in 2nd generation Cambodian American (CA) young adults. A total of 66 participants who identified as being 2nd generation CA young adults aged 18-25 years old were recruited to participate in this cross-sectional. Reliable and valid measures were used to assess protective and risk factors and mental (depressive, anxiety, somatic symptoms) and behavioral health outcomes (alcohol and drug use). We used descriptive statistics to describe sample characteristics and study variables and conducted multiple regression analysis to examine the associations of factors with each of the 5 health outcomes. The findings suggested that peer discrimination was positively and significantly associated with depressive (β = 0.42, p = 0.023; R2 = 0.397) and somatic symptoms (β = 0.63, p = 0.000, R2 = 0.554). Father role-reversal was also found to be negatively and significantly associated with predicting CA young adults’ anxiety symptoms (β = -0.32, p = 0.005, R2 = 0.456).

Majority of the CA young adults have perceived racial/ethnic discrimination in the community. Furthermore, perceived discrimination has been positively associated with their depressive and somatic symptoms, suggesting a need to address racial/ethnic discrimination issues to promote positive mental health in this population. It is important for school/work personnel and healthcare providers to assess CA young adults’ discrimination experiences, and have the sufficient resources (e.g., education, support groups) to prevent negative consequences associated with discrimination.

Contributors

Agent

Created

Date Created
  • 2015-12

135905-Thumbnail Image.png

Asthma ICAM-1 2: The Effects of Vitamin C on s-ICAM Expression

Description

This study was conducted to observe the effects of vitamin C supplementation upon the expression of sICAM-1 in asthmatic subject. Two groups were created, each with a sample size of

This study was conducted to observe the effects of vitamin C supplementation upon the expression of sICAM-1 in asthmatic subject. Two groups were created, each with a sample size of 4 subjects. One group was the vitamin C group (VC) and the other was the placebo group (PL). The study was analyzed through observing concentrations of biomolecules present within samples of blood plasma and nasal lavages. These included vitamin C, sICAM-1 expression, and histamine. The following P-values calculated from the data collected from this study. The plasma vitamin C screening was p=0.3, and after 18 days of supplementation, p=0.03. For Nasal ICAM p=0.5 at Day 0, p=0.4 at Day 4, and p=0.9 at Day 18. For the Histamine samples p=0.9 at Day 0 and p=0.9 at Day 18. The following P-values calculated from the data collected from both studies. The plasma vitamin C screening was p=0.8, and after 18 days of supplementation, p=0.03. The change of vitamin C at the end of this study and the combined data both had a P-value that was calculated to be lower than 0.05, which meant that this change was significant because it was due to the intervention and not chance. For Nasal ICAM samples p=0.7 at Day 0, p=0.7 at Day 4, and p=1 at Day 18. For the Histamine p=0.7 at Day 0 and p=0.9 at Day 18. This study carries various implications although the study data was unable to show much significance. This was the second study to test this, and as more research is done, and the sample size grows, one will be able to observe whether this really is the mechanism through which vitamin C plays a role in immunological functions.

Contributors

Agent

Created

Date Created
  • 2015-12

135910-Thumbnail Image.png

Combination Treatment for Full Thickness Wounds: Platelet-Rich-Gels and Electro-Spun Collagen Scaffolds

Description

Full thickness wounds encompass damage through the epidermis and dermis with characteristic loss of structure and healing through secondary intention. Two treatments that have been thoroughly researched and shown efficacy

Full thickness wounds encompass damage through the epidermis and dermis with characteristic loss of structure and healing through secondary intention. Two treatments that have been thoroughly researched and shown efficacy in treating these types of wounds are platelet-rich-gels (PRG) and electro-spun collagen scaffolds. However, little research has been done to investigate the two as a combination treatment, a biomaterial enrich platelet-rich-gel. PRGs provide the wound with growth factors and cytokines that are naturally present in a wound bed, but in a concentration above that of native physiological conditions. The electro-spun collagen scaffold works on two premises, the first is that it is providing a vital skin protein that will be deposited during the wound healing process in addition to providing a matrix for cells to migrate into. The investigation into PRGs and the combination treatment was ultimately accomplished in a three step study: creation of a PRG from platelet-rich-plasma (PRP) utilizing calcium chloride; analysis into the effects of calcium chloride on platelets through scanning electron microscopy; and finally an in vivo study comparing two treatments, the combination treatment and standalone electrospun scaffold treatment, and a control (dressed with petroleum gauze). Calcium chloride revealed to be an effective method for gel creation. SEM analysis detailed whole blood platelets demonstrating normal discoid morphology found in quiescent platelets, whereas the PRG platelets demonstrated extending pseudopods and bleb formation indicative of activation. In the in vivo study, both the standalone electro-spun collagen scaffold treatment and the combination treatment had statistical significance 144 hours post wound creation when compared to the control with p values of 0.0092 and 0.0016 respectively. However, there was no statistical significance between the combination treatment and the standalone electro-spun scaffold treatment at any time point of the study.

Contributors

Agent

Created

Date Created
  • 2015-12

Evolutionary perspective suggests candidate genes for variation in Turner Syndrome phenotype

Description

Tremendous phenotypic variation exists across people with Turner syndrome (45,X). This variation likely stems from differential dosage of genes on the X chromosome. X-inactivation is the process whereby all X

Tremendous phenotypic variation exists across people with Turner syndrome (45,X). This variation likely stems from differential dosage of genes on the X chromosome. X-inactivation is the process whereby all X chromosomes in excess of one are silenced. However, about 15% of the genes on the silenced X chromosome escape this inactivation and are candidates for affecting phenotype in people with Turner syndrome. In this study we take an evolutionary approach to rank candidate genes that may contribute to phenotypic variation among people with Turner Syndrome. We incorporate analysis of patterns of DNA methylation from 46,XX and 45,X individuals, and estimates of variable X-inactivation status across 46,XX individuals, with patterns of gene expression conservation on the X chromosomes across five tissues and ten species. We find that genes that escape XCI are possible candidate genes for Turner syndrome phenotype, indicated by the constant levels of expression in escape genes and inactivated genes. Variation in these genes is expected to affect phenotype when dosage is altered from typical levels.

Contributors

Agent

Created

Date Created
  • 2015-12