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Senior, Biological Sciences
Co-researchers: R. Moniri, S. B. Singh, E. Reed, J. P. Gizicki, S. Noman, A. S. Basu, J. L. Ram
Faculty mentor: Dr. Jeffrey L. Ram, Department of Physiology
Automated Testing Device for Live-Dead Analysis of Ballast Water Organisms
Methods for verifying ballast water treatments are needed to protect the Great Lakes from discharge of live non-native organisms or pathogens. Here we describe prototypes for automated viability testing using fluorescein diacetate (FDA), a membrane permeable fluorogen, to differentiate live from dead bacteria and algae. An automated system captured lab cultured, environmental, or ballast organisms on 0.2 um filters, backwashed them with buffer and FDA for subsequent fluorescence measurements, and washed the filters with sterile water for serial automated reuse. Preliminary manual versions of these procedures were also tested. Fluorescence in the presence of live organisms increased linearly over time and decreased linearly with sample dilutions (r2=0.92). After plankton and ballast water treatment with heat or chlorine, fluorescence was greatly decreased, to levels near control (sterile water). Cost reductions in the detection system included changing from fluorescence plate reader (>$20,000), to a fiber optics spectrometer (~$5,000), to recent electronic prototypes costing <$500. Automated measurements of FDA hydrolysis with a reusable filter backwash system under computer control should be applicable to real-time remote-controlled monitoring of live organisms in ballast water (patent pending).
Faculty mentor: Dr. Eric Montgomery, Honors College
Gorovodu Medicine Amongst the Ewes of Ghana and Togo
Western medicine is beginning to pay more attention to indigenous systems of plant medicine throughout the world. Most of this attention has been focused in Asia, but Africa is also worthy of further investigation as well. When biomedicine does investigate traditional medicine, it does so through a Western lens and rarely takes into account local meanings and contexts. Also, clinical trials attempt to isolate the properties of certain plants and also ignore local meanings and the importance of ritual. Ritual plays a very important role in the healing process.
On the other hand, anthropologists focus on traditional systems of healing but rarely delve into the biochemical properties of plants. This research bridges these informal divides: Western/Traditional, Global/Local and Allopathic/Indigenous. It explores the medical-religious healing practices that are followed by Gorovodu and describes how spiritual and natural forces help in the process. In addition, it analyzes how the botanical and biochemical properties of the indigenous plants are used in Gorovodu healing and religion’s role in the healing process.
Senior, Biochemistry and Chemical Biology
Co-researchers: Danielle N. Dremann, Alain Bretous, Moninderpal Kaur, and Christine S. Chow
Faculty mentor: Dr. Christine S. Chow, Biochemistry Division
Development of Bead-Based Assays for RNA-Ligand Discovery
Helix 69, or H69, of the ribosome plays a key role in initiation and termination of translation. Small-molecule binding to this region could lead to inhibition of protein synthesis, an essential process throughout phylogeny. The H69 region of bacteria has been shown to bind certain peptides selectively, which may lead to new antimicrobials. The goal of this study is to identify compounds that bind to H69 by developing and using an optimized fluorescence-based assay. The assay uses TentaGel beads with bound synthetic peptides, biotinylated H69, and streptavidin-tagged quantum dots (Qdots). The interaction of H69 with the immobilized peptide is indicated through Qdot emission, which is visualized under a fluorescence microscope. The relative fluorescence values were quantified. A complementary colorimetric assay is also being developed. In the future, these assays will be used to identify new binding ligands for H69.
Faculty mentor: Dr. Liette Gidlow, Department of History
Ads of Identity: Trends in African American Beauty Advertisements 1934-1980
African American identity in America has always been complex and debated even amongst African Americans. With the sense of always being judged, African Americans had to determine how to best fit into society1. One solution that arose prominently amongst African America women was the use of makeup products to help present themselves in the best light. These products included face powders, hair pomade, and even skin whiteners and hair straighteners. The latter two products were questionable because they did not espouse natural African beauty. The ads for these beauty products, even placed in popular African American newspapers such as the Atlanta Daily World, could then be used to gauge society’s and African Americans’ shifting attitudes about their identity and how they deemed it best to fit into society2. An analysis of the Atlanta Daily World from 1934 to 1980 revealed that no such controversial ads were printed after 1964, the year the Civil Rights Act was passed and as the Black Power movement began to gain momentum. An analysis of Ebony, a popular African American newspaper, revealed that the same companies who espoused skin whiteners and hair straighteners in the Atlanta Daily World were now promoting the same products with taglines that advocated natural African beauty. This change is truly reflective of the Black Power Movement as the goal of the movement was to instill a sense of racial pride and community within African Americans. This change in the direction of the African American beauty industry throughout the period that encompassed both the Civil Rights Era and the Black Power movement makes it safe to conclude that African American identity was influenced by these two movements and heralded an era of greater African pride.
Senior, Biomedical Engineering Honors
Co-researchers: Nicholas A. Mischel and Patrick J. Mueller
Faculty mentor: Dr. Patrick J. Mueller, Department of Physiology
Physical (in)activity-induced changes in tonic excitation and inhibition in the rostral ventrolateral medulla (RVLM)
The RVLM contains neurons that regulate blood pressure and exhibit (in)activity-dependent neuroplasticity. Previous studies have found that sedentary animals have enhanced responses to direct activation of RVLM neurons that regulate sympathetic nervous activity (SNA). We hypothesized that sedentary animals have heightened sympathoexcitation due to enhanced glutamatergic and/or attenuated GABAergic neurotransmission. Rats were housed with or without running wheels for 12 weeks and were then anesthetized with Inactin and instrumented to record mean arterial pressure, heart rate, and splanchnic SNA during microinjections into the RVLM. The RVLM was functionally identified by a pressor response to glutamate (30 nl, 100 mM). Bilateral blockade of GABAA receptors with bicuculline (5mM) was performed either alone or following bilateral injection of the ionotropic glutamate receptor antagonist kynurenic acid (40 mM). Sedentary versus active rats displayed a greater SNA response following bicuculline injection alone (Δ62±7% v Δ38±8%, p<0.05). The SNA response to bicuculline after injection of kynurenate was attenuated in sedentary rats (Δ62%±7 v Δ 28%±5, p<0.05). Active rats did not show a significant SNA attenuation (Δ38±8% v Δ31±6%, p>0.05). These findings suggest that the exaggerated SNA increase in sedentary versus physically active rats following GABAA blockade is mediated by enhanced activation of ionotropic glutamate receptors. This study further demonstrates (in)activity-dependent alterations in the RVLM and these changes may contribute to an increased risk for cardiovascular disease in sedentary individuals.
Junior, Biochemistry and Chemical Biology
Faculty mentor: Dr. Judith Whittum-Hudson, School of Medicine Department of Immunology and Microbiology
Folate-Functionalized Nanoparticles Targeted Anti-Chlamydial Drug Delivery
Our studies demonstrate the increased efficacy of Folate-targeted Nanoparticles for delivering Azithromycin and Rifampicin drug combinations to Chlamydia-infected cells in vitro. The use of targeted nanoparticles significantly reduced chlamydial inclusion size, numbers and transcripts of the chlamydial 16S rRNA gene, demonstrating an increased drug efficacy when compared to non-targeted antibiotic treatments at the same concentrations. These results support fundamental savings in public health costs and will help facilitate effective anti-chlamydial treatments worldwide. Furthermore, Folate-targeted nanoparticles are highly effective in treating persistent chlamydial infections which are very refractory to free drugs in soluble form.
Senior, Public Affairs
Co-researchers: Ashley Burgess, Richard White, Raj Ramasubbu, Vaibhav Diwadkar
Faculty mentor: Dr. Vaibhav Diwadkar, Department of Psychiatry
Brain Connectivity Changes Following AntiDepressant Treatment in Major Depressive Disorder
Background: Major Depressive Disorder (MDD) is a common and recurrent condition characterized by changes in mood, bringing about sadness or irritability. Whereas the neural network bases for MDD is still poorly understood, disordered reactivity of core regions of the limbic system such as the amygdala have been implicated. The amygdala is associated with the processing of emotion, and particularly fear and anxiety related stimuli (Asan, Steinke et al. 2013). Moreover, the amygdala and the limbic system are densely connected with regions such as the prefrontal cortex. Therefore understanding network interactions associated with treatment response assumes particular significance.
Methods: During fMRI, 46 subjects with MDD participated in a picture-matching task (Hariri et al., 2003) during which subjects’ matched pairs of faces (or geometric objects) among triads (three faces or three objects). Analyses focused on comparing amygdala connectivity with other brain regions when responding to negatively valenced faces (compared to the control stimuli, i.e., objects). To assess amygdala connectivity, psychophysiological interactions (PPI) were computed for each subject, with the time series from bilateral amygdala seeds convolved with the contrast of interest (Faces > Objects). The resultant interaction term represents the modulatory effect of the seed (amygdala) on target brain regions, during the task. Subjects performed fMRI at three time points (baseline, Wk1, and Wk8) during an ongoing treatment trial. To assess time (i.e., treatment) effects on amygdala connectivity, interactions maps for all subjects were submitted to a 2nd level analyses of variance with time and treatment as factors. The current results focus in the effect of time.
Results: Two salient results were observed. First, amygdala modulation of frontal and cingulate regions increased over time/treatment. These effects observed at Wk1 were particularly amplified at Wk8. Second, comparing responders (patients with a significant amelioration of symptoms) to non-responders, indicated that the effects were most marked amongst responders, who at the Wk8 time point, showed significantly greater amygdala-frontal connectivity than non-responders.
Conclusion: Clear treatment-effects were observed on limbic-frontal connectivity, suggesting that anti-depressant treatment may normalize limbic inputs to the cortex. Moreover, the results were particularly salient in responders, further emphasizing the functional role of anti-depressants in normalizing functional interactions between limbic and frontal brain regions. These effects imply that anti-depressants enhance limbic signaling to cortical regions, and the correction in this signaling may positively affect changes in the depressive phenotypes. Our ongoing studies are investigating cortical-limbic changes (i.e., top-down) as a function of treatment and treatment response.
Senior, Nursing Honors
Co-researchers: Angulique Outlaw, Sylvie Naar-King, Steven P. Woods, Psy. D, and the PM Investigator Team
Faculty mentor: Dr. Angulique Outlaw, Department of Pediatrics
Youth Perspectives on Proposed Medication Adherence Interventions for Youth Living with HIV
Adherence studies focusing on HIV medication adherence for behaviorally infected youth living with HIV (YLH) suggest adherence patterns that are not adequate to effectively manage the disease. Adherence to antiretroviral treatment (ART) is a significant predictor of virologic suppression and is associated with dramatic reductions in mortality and morbidity for persons with HIV. Therefore, interventions inclusive of the perspectives of YLH are needed to improve medication adherence. The current study is part of a larger study to develop and conduct a pilot randomized clinical trial of a prospective memory adherence intervention for YLH. Participants (N=18; ages 21-24) completed a semi-structured interview (face-to-face or via phone) about proposed medication adherence interventions for YLH. Interviews were audio recorded (when possible) and content analyses were used to describe and categorize data. Preliminary findings suggest that participants’ reported reasons medication adherence consistent with the existing literature (i.e., forgetting, busy, tired, denial/stigma). The majority of participants did not feel they needed intervention for adherence to HIV medications (65% for home-based services vs. 56% for text reminders). However, brief (30 – 60 minute sessions; 1 – 2 text reminders per day), short-term (1 – 2 home-based visits per month; home visits for 1 – 6 months; text reminders for 1 – 3 months), consistent interventions (same person visits to build rapport; same number of text reminders for the duration of the intervention) were recommended. In conclusion, brief, short-term, consistent interventions were proposed by YLH and may be effective to improve medication adherence for this population.
Senior, Nutrition and Food Science, Slavic Studies, and Psychology
Co-researchers: Nadia Saadat
Faculty mentor: Dr. Smiti Gupta, Department of Nutrition and Food Science
Bad Blood: A hematological analysis of the effects of an OPP-rich diet on the lymphocyte profiles of transgenic pancreatic cancer mice
With over 40,000 new cases and 37,000 deaths affecting the American populace annually, pancreatic cancer has established itself as one of the most lethal diseases of the modern age. This information, combined with the very poor five-year survival rates after diagnosis with the cancer, elicits a need for more effective therapies to be developed in the treatment of the disease. One of the nutraceuticals under investigation, the use of oil palm phenolics (OPP), has seen marked results in current research when used to treat both degenerative chronic diseases and tumor progression in cell culture and mice models. Though the exact mechanism of OPP in cancer reduction is unknown, we hypothesized OPP would have a positive effect on the levels of cancer-fighting natural killer (NK) cells, leading to the nutraceutical’s anti-cancer properties. In order to test the effects of an OPP diet on the lymphocyte profiles of transgenic pancreatic cancer mice, we investigated the number of both NK and non-NK lymphocyte cells in the blood smears of these mice while following an OPP-rich regimen. The results indicate an exciting future for the use of OPP in anti-cancer therapies, as the experimental OPP diet was shown to be more effective in increasing the average number of NK cells in both cancer and control mice than mice not on the diet. Though the results seem to confirm the hypothesis that an OPP-rich diet alone may elevate NK cell levels, further research on the underlying mechanism of OPP in cancer reduction was deemed necessary to substantiate this claim.
Faculty Mentor: Dr. Alina Klin, Department of Classical and Modern Languages, Literatures, and Cultures (Slavic Studies)
Przeszczepiać albo nie przeszczepiać?: To Transplant or Not to Transplant? A Quantitative Approach to how Health Science Students in Poland Approach Questions of Transplantation
To investigate a possible link between progression through health science education and attitudes towards cell and organ transplantation in Polish health science students (future doctors, nurses, paramedics, public health specialists, etc.), anonymous surveys completed by 101 health science students from the Medical University of Łódź were conducted at a summer camp retreat in Łazy, Poland in August 2011. The results show several correlations between the amount of education in a student’s chosen career path and his or her acceptance of cell and organ transplantation techniques as treatment methods. Though the percentages of students giving positive responses to the importance of religion and profession of Catholic faith remain steady throughout their educations, knowledge of Poland’s legal regulations concerning transplants, approval of adult and embryonic stem cell treatments, and acceptance of human embryo research find increasing support among students as they reach the terminal years of their medical educations.
Faculty mentor: Antonie W. Y. Walsh, School of Business Administration
New Michigan Corporate Income Tax System Good for Business – Maybe – But at What Cost?
Changes to Michigan’s tax system went into effect in the later part of 2011 and early 2012. The Michigan Business Tax was replaced by the Corporate Income Tax. The new income tax that applies to businesses is a more simplified calculation and lesser flat tax rate of 6% with the intent to attract new businesses and a productive workforce to the state. However, lowering the tax on corporations causes a revenue deficit. How does Michigan account for the loss in tax revenue generated by businesses? The Income Tax Act was amended to reflect the elimination of credits, deductions, and exemptions, along with tax rate changes for individuals. In particular, pension and retirement income have become taxable. Effectively, the tax burden seems to have shifted onto retirees and also begs the question of whether or not the older households respond to such income tax changes and if these responses are exclusive. What factors do retirees consider when evaluating the desirability of a state? Furthermore, has unemployment decreased and has Michigan’s population grown?
Faculty mentor: Dr. Fu-Shin Yu, School of Medicine Department of Ophthalmology
Identification of differentially expressed genes between homeostatic and healing rat corneal epithelial cells
Corneal epithelial renewal performs the essential role of preventing infectious agents from penetrating the eye’s primary barrier. Epithelial wound healing is a well-coordinated action that involves the combined efforts of numerous genes and different cell types. Compared to other tissue, corneal epithelial closure is a relatively simple biological process driven by cell migration. To elucidate the differential gene expression between homeostatic and healing rat corneal epithelial cells, we completed a comprehensive analysis of their gene profiles using the affymetrix GeneChip® Rat Genome 230 2.0 Array. Following normalization of raw data from three biological replicates using 3177 probes shown in excess of a 2-fold change with p-value smaller than 0.05 (N=3) for gene expression between homeostatic and healing corneal epithelial cells, 1811 genes were identified. Among the identified genes, 95 are transcription factors, notably, upregulated activating transcription factor 3, heat shock transcription factor 2 and 3, early growth response genes, and dowregulated peroxisome proliferator-activated receptor-γ. The second group includes 115 wound response genes such as antimicrobial peptides, growth factors and receptors, matrix metallopeptidases and their inhibitors, cytokines, and chemokines. As epithelial wound healing involves the actions of cell adhesion, migration, proliferation, differentiation, and death, 401 genes identified may participate in 1 or more biological events, leading to wound closure. Using these data, three regulatory networks (MMP-mediated signaling, inflammatory cell signaling, and regulation of cell migration) were constructed. Taken together, these novel gene expression signatures provide new insights and clues into the mechanisms underlying epithelial wound healing and new therapeutic targets for accelerating delayed epithelial wound healing such as that observed in diabetic corneas.
Junior, Biological Sciences
Faculty mentor: Dr. Robert Akins, School of Medicine Department of Biochemistry
Antifungal Resistance in Candida Albicans
Antifungal resistance is a growing problem due to the limited number of antifungal drugs, and because resistance arises both from intrinsic resistance of species and acquired resistance by mutation or adaptation in exposed populations of sensitive species. The second category is and will continue to increase as antifungal use becomes more widespread in aging and immunocompromised patient groups. While many targets of antifungal drugs are identified, regulators of their expression are not, and these are not easily recognized solely by sequence homology among fungal species. A functional assay to identify these genes is needed. Dr. Akins has developed a high copy shuttle plasmid in C. albicans, the most prevalent fungal pathogen, in which cloned genes from a genomic DNA library are present at up to 50 times their normal copy number and are overexpressed. When this changes antifungal sensitivity, it implicates the cloned gene in the mechanisms the cells use in response to the antifungal.
Previous work by WSU Honors undergraduates and 1st year medical students has identified three cloned genomic DNA fragments from a library whose overexpression results in antifungal resistance. One of these fragments contains two adjacent zinc finger protein genes and results in resistance to all echinocandins (micafungin, caspofungin, anidulafungin; beta-glucan synthase inhibitors) but not to other classes of antifungals. A second clone contains two adjacent genes of unknown function and confers resistance to miltefosine, which has broad-spectrum antifungal activity but an understudied mechanism of action, thought to act as a plasma and/or mitochondrial membrane disruptant. The third clone contains three adjacent genes and causes both resistance and hypersensitivity to a many antifungals acting in multiple pathways. My objective is to identify the individual gene in each of these three clones that is causing the altered resistance phenotype. I will approach this by cloning each of these genes, using PCR on genomic DNA, to include upstream and downstream regulatory sequences for each gene, into the high copy plasmid. I will transform these into C. albicans. Using this method the expected results are either the responsible genes will confer the resistance profiles seen in the original transformants or resistance resulting from overexpression regulatory genes will act by altering expression levels of known resistance genes, such as the target gene, efflux genes, etc. The significance of these studies centers on the idea that commercial antifungals may be improved by appropriate synergistic agents that block activation of compensatory pathways or efflux. Understanding how target pathways are regulated and how multiple pathways can interact is a key step towards this goal.