Undergraduate Research Day 2021

Permanent URI for this collectionhttp://hdl.handle.net/1903/27016

With students involved in so many research opportunities, Undergraduate Research Day provides the perfect opportunity for them to share their work with the campus community. Held each April, Undergraduate Research Day showcases current research, scholarship, and artistic endeavors.

Browse

Now showing 1 - 20 of 25

Implications of the TCA Cycle on Escherichia coli Growth and Phage Replication
(2020) Suriaprakash, Aiswarya; Bokil, Eesha; Koudouovoh, Carlos; Chuck, Marissa; O'Hara, Jessica
ATP provides energy for the cellular processes in E. coli. The E. coli icd gene encodes the enzyme isocitrate dehydrogenase which is used in the tricarboxylic acid (TCA) cycle to make ATP. We hypothesize that T4 phage is dependent on ATP production in the host cell in order to successfully replicate. Our research aims to find if an E. coli bacteria strain lacking the icd gene will show decreased T4 phage replication because of its decreased ATP production compared to E. coli bacteria strains that possess the icd gene with normal ATP production. Decreased ATP production in the E. coli host will result in a decrease in bacterial growth rate and T4 phage replication. Plaque assays, growth curves, and lysis curves were used to monitor bacterial growth and phage replication. Host cells lacking the icd gene had decreased bacterial growth. T4 phage replication is slower in the host cells lacking the icd gene. It is the hope that these results and future research will contribute to phage therapy, a promising development in treating bacterial diseases.
Investigating Arginine Biosynthesis in Viral Replication
(2020-11) Lee, Harrison; Griffin, Ryleigh; Stecklein, Sabrina; Chaudry, Daniel; O'Hara, Jessica
When a virus infects a cell, it must hijack that host cell’s inner machinery, normally used to manufacture necessary molecules for the host cell, and divert that machinery to producing new viruses. Previous research has indicated that arginine, an amino acid, plays an important role in viral infection. We investigated the role arginine plays in infection in two ways. First, we compared how well bacteriophage, a type of bacteria-infecting virus, replicated in normal (parent) E. coli and genetically modified E. coli that could not produce their own arginine. These genetically modified E. coli are called a knock-out strain because the gene for a particular protein, in this case an enzyme involved in producing arginine, is removed. The gene in question is called argH and thus the knock-out strain is named ΔargH. Here we found that when arginine was available from outside the cell, there was no significant difference between bacteriophage replication in the two E. coli strains. Second, we observed how the levels of certain small molecules (metabolites), including arginine, inside a human cell changed after it was infected with the Human Cytomegalovirus (HCMV). We found that HCMV infected cells had altered levels of metabolites from throughout the arginine biosynthesis pathway, including increased levels of arginine.
The Deprioritization of Gender and Protection During UNRWA’s 2018 Financial Crisis
(2021) Greenwald, Erica; Kosko, Stacy; Tuke, Daniel
On August 31, 2018, the United States Department of State announced their termination of all funding to the United Nations Relief and Works Agency for Palestinian Refugees in the Near East (UNRWA). Prior to 2018, the United States government was UNRWA’s largest donor and a leading advocate for the agency’s role in stabilizing the Middle East. Though UNRWA has historically faced funding challenges, the termination of U.S. funding plunged the agency into an unprecedented financial crisis. During emergencies—health, economic, military, or otherwise—gender work has often been relegated to non-essential status, limiting the quality and inclusivity of humanitarian response. This research considers how UNRWA’s gender and protection work was impacted by the agency’s 2018 financial crisis. Ultimately, I find that UNRWA’s institutional structure did not sufficiently value gender work, relegating this approach to non-essential status in crisis and making it especially vulnerable during budget cuts. As a result of these vulnerabilities, UNRWA dismantled gender and protection, ending targeted interventions, oversimplifying mainstreaming efforts, and exporting their work to non-experts. This paper also considers the implications of deprioritizing gender work: increasing gender-based violence, regional instability, and a self-reinforcing cycle of vulnerabilities. Moreover, this paper examines the connection between community and gender-based violence and its relation to violent extremism. Despite the vital importance of gender and protection work, as well as efforts to integrate this work in with other program lines, these programs are seen as nonessential and are routinely hit first and worst during budgetary crises.
Autocycle: Design, Construction, and Validation of an Autonomous Bicycle
(2021) Allen, Michael; Bartolomei, Jacob; Carter, Jeremy; Grill, Cooper; Khrenov, Mikhail; Mirenzi, John; O'Leary, Joseph; Rose, Isaac; Ruderman, Evan; Sanguesa, Andoni; Swaisgood, Logan; Gomez, Romel
Efficient urban transportation has time and time again proved to be a difficult problem to rectify. One modern solution is the bike-sharing system, where many bicycles are available either at hubs or spread across a city for short-term use. However, usage is limited to those located close enough to a bicycle hub that traveling to and from it is time-effective. As for hubless bike-shares, bicycles require redistribution over time to remain conveniently available to many. We propose the creation of an electric bicycle that can either be used by a cyclist manually or operated autonomously using locomotion, sensing, balance, and control systems. We have concluded that such a concept is possible and achievable, as we are making significant progress toward developing working prototypes for the self-stability and autonomous navigation of the Autocycle. Once those milestones are completed, we will integrate the two systems together in the final prototype. Our Undergraduate Research Day presentation will showcase the research and data we have collected up until this point and outline our future goals for the project. With the completion of this prototype, we want to show that such a bicycle could be implemented into a larger bike-sharing system that autonomously manages distribution and allows users to summon a bicycle to their location, expanding the range of use and encouraging environmentally-friendly transportation solutions in an urban setting.
An Archival Look at Being Alone Versus Being Lonely: Impact on Social Anxiety Posts on Reddit
(2021) Lazo-Salmeron, Wilson; Follet, Lia; Tomlinson, Tracy
Given the global COVID pandemic, people are isolating and reducing social contact in unprecedented ways. As individuals experience loneliness, they also may exhibit social anxiety, possibly due to a reduced sense of security while feeling vulnerable. (Hawkley & Cacioppo, 2016). However, despite this relationship, research is unclear if social anxiety is associated with being alone (i.e., absence of others) or the added condition of loneliness, otherwise defined as the perception of social needs not being fulfilled (Hawkley & Cacioppo, 2016). We conducted two naturalistic-observational designs to compare social anxiety posts of Reddit users who were responding to posts about loneliness or being alone. The first study compared lonely individuals to those with a more positive perception of being alone. Sixty participants (33.33% male, 18.33% female, 48.33% unknown) were sampled from Reddit, a forum-based community. Participants were coded as lonely if they responded to a Reddit page asking how to cope with loneliness, while individuals were coded as being alone if they responded to a Reddit page asking if alone time is healthy. The second study compared social anxiety amongst lonely individuals surrounded by others and lonely individuals while alone. Once again, 60 participants were sampled from Reddit. We coded participants as lonely with others if they responded to a page describing loneliness in the presence of others or lonely and alone based on a page detailing acceptance of the two. Social anxiety was coded based on the frequency of social anxiety symptoms (e.g., withdrawal, embarrassment, etc.) present in each sentence within each participant's comment. Study one results indicate a medium to large effect of loneliness (t(34.1) = 2.85, p < .05, d = .74), such that lonely individuals expressed greater social anxiety compared to alone participants. The results of the second study also found a medium effect of loneliness (t(58) = 2.07, p < .05, d = .53) as lonely individuals surrounded by others described more social anxiety comments than those who are lonely and alone. Overall, there is a medium effect size concerning both studies. Consequently, these findings are consistent with past research regarding loneliness being correlated with social anxiety (Acquah et al., 2016; Gallagher et al., 2014). Additionally, results are compatible with the theory that loneliness is associated with negative effects while being alone is a neutral state that can potentially lead to positive feelings (Buchholz & Catton, 1999). Future research may explore demographic traits that differ between individuals who are alone and lonely and how these potential personality traits relate back to social anxiety. Furthermore, research may investigate if there are more conscious mechanisms that alone people employ to reduce loneliness. Consequently, this may be implemented in intervention across susceptible groups to loneliness, such as minorities, as they may perceive a social disconnect with others due to dissimilarity. More globally, intervention may examine how to combat the loneliness the COVID pandemic has forced upon individuals (Loades et al., 2020).
Identification of Clostridium Phage Endolysins with Novel Multimeric Genetic Sequences
(2021) Bokil, Eesha; Baker, Charley; Nelson, Daniel; O'Hara, Jessica
The endolysin CD27L is produced by the Clostridium phage phiCD27. This phage targets the bacteria and uses the endolysin’s enzymatic properties to lyse cells from within and release new replicated phages. Past studies have characterized the two domains of CD27L’s genetic sequence, the enzymatically active domain (EAD) at the N-terminus and the cell wall binding domain (CBD) at the C-terminus connected by a linker sequence. The gene sequence order is EAD-linker-CBD. A unique aspect of CD27L is its ability to form a multimeric enzymatic structure from these two domains where one EAD and multiple CBDs are present in one structure. This multimeric endolysin is formed from one gene, so translation of the one sequence uses two ribosome binding sites and two start codons. One ribosome binding site and start codon is before the EAD and the other in the linker sequence before the CBD. Our goal is to analyze the sequences of other Clostridium phage endolysins to find multimeric endolysins similar to CD27L. We are specifically looking for multiple ribosome binding sites with start codons or alternate start codons downstream in close proximity on one gene sequence.
Early Intervention with Repurposed Drugs to Treat COVID-19
(2021) Bhalwani, Sofia; Siddiqui, Aamna; Matharu, Sagar; Srinivasan, Keerthana; Vellala, Sourabh; Arora, Amit; Mangat, Harpal; Sahi, Apanjit; Mangat, Harpal
Background: Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus responsible for the Coronavirus disease 19 (COVID-19) pandemic. A hallmark of the virus is its spike protein, which interacts with the angiotensin-converting enzyme 2 (ACE-2) receptor to invade the cell. After entry, SARS-Cov-2 hijacks existing cellular machinery to self-replicate. The virus binds to the ACE-2 receptors and activates bradykinin production. Early symptoms of COVID-19 include dry cough, sore throat, fever, chills, muscle aches, diarrhea, abdominal pain, shortness of breath, and loss of taste and smell. Repurposed drugs were used to treat COVID-19 early, preventing complications of a deadly cytokine storm that starts around day 10. This study evaluates the effectiveness of these repurposed drugs. Methods: A retrospective observational study to review the efficacy of treatment by measuring symptom resolution. Quantitative symptomatic data was observed for 26 patients (9 patients were 55+) with a lab-confirmed, positive SARS-CoV-2 test. Patients' symptoms improved rapidly in the first ten days. Symptom plot analysis over time with correlation coefficient for each medicine was examined. The medicines were lopinavir/ritonavir (Kaletra), bamlanvimab (monoclonal antibody), glycopyrrolate-formoterol (Bevespi), ciclesonide (Alvesco), famotidine (Pepcid), and diphenhydramine(Benadryl). How each medication works on Covid pathways is shown. Results: Out of 26 patients, eight (30.8%) were treated with lopinavir/ritonavir, bamlanvimab, glycopyrrolate-formoterol, ciclesonide, and diphenhydramine. Patients experienced a rapid improvement in COVID-19 symptoms within 3 - 5 days. The correlation coefficients for each medicine and the number of symptoms were determined. The more negative the faster the resolution of symptoms: Correlation coefficient for Kaletra -0.1407, Bevespi -0.227, Alvesco -0.2191, famotidine -0.1554 Conclusion: Early treatment, with a combination of the repurposed drugs Kaletra, Bevespi (glycopyrrolate-formoterol), Alvesco (ciclesonide), Benadryl (diphenhydramine), Monoclonal Antibodies (bamlanvimab), and Pepcid (famotidine)] interrupts the viral life cycle and prevents the progression into a cytokine storm.
Gene Targeting Techniques for Huntington's Disease
(2021) Fields, Eric; Vaughan, Erik; Tripu, Deepika; Lim, Isabelle; Shrout, Katherine; Conway, Jessica; Salib, Nicole; Lee, Yubin; Dhamsania, Akash; Michael, Jacobsen; Woo, Ashley; Cao, Kan
Huntington’s disease (HD) is an autosomal neurodegenerative disorder caused by extended trinucleotide CAG repetition in the HTT gene. Although this mutation in the HTT gene is mostly associated with neurological and physical symptoms that HD typically exhibits, wild-type Huntingtin protein (HTT) is involved in a variety of cellular functions such as vesicle transportation, cell division, transcription regulation, autophagy, and tissue maintenance. The main cause of HD symptoms is due to aggregation and accumulation of mutant HTT (mHTT) proteins in neurons. In this review, we discuss multiple approaches targeting DNA and RNA to reduce mHTT expression. These approaches are categorized into non-allele-specific silencing and allele-specific-silencing using SNPs and haplogroup analysis, and the possible limitations of targeting mHTT is also discussed. Additionally, this review discusses am potential appliction of recent CRISPR prime editing technology in treating HD.
Impact of Inhibition of the TCA cycle on ATP and NADH levels in Escherichia coli during Bacterial Replication
(2021) Suriaprakash, Aiswarya; Mercado, Briana; De La Cruz, Raina; O'Hara, Jessica
Bacteriophage are bacteria-eating viruses that utilize the host cell’s metabolic pathways for components for phage replication. The tricarboxylic acid (TCA) cycle, an important metabolic pathway within cellular respiration, uses oxygen to break down organic molecules to make adenosine triphosphate (ATP) for energy. In E. coli, the fumarase A gene codes for the enzyme fumarase, which catalyzes fumarate to (S)-malate and NAD+ in the TCA Cycle, used to create NADH, pyruvate, high-energy electron carriers, and ATP. The icd gene encodes the enzyme isocitrate dehydrogenase which is also used in the TCA cycle to make ATP. In our previous research, we discovered that the removal of the fumA and icd genes resulted in a delay in T4 and/or T4r bacteriophage replication. Currently, we are aiming to quantify ATP and NADH levels before and after cell lysis to further understand the impacts of each knockout on cellular metabolism and the resulting impact on T4 replication. This research is made to further understand ways to treat bacterial diseases in the face of antibiotic resistance, specifically phage therapy.
Content Analysis Versus Structured Topic Modeling: Unethical Military Leadership
(2021) Cheng, Virginia; Hsiao, Kimberly; Smolko, Braden; Epistola, Jordan; Hanges, Paul; Hanges, Paul
The U.S. Military strives to reduce unethical behavior in the organization by identifying and targeting unethical leaders. This qualitative study employs content analysis and the structured topic modeling machine learning algorithm to understand unethical leadership in the Military on over 439 interviews with military personnel at six different locations. Specifically, we compared the results of both approaches to identify important aspects of unethical leadership in the Military. In general, both methods produced similar results that supported one another. Moreover, the STM method produced new insights of unethical leadership that were highly interpretable by the research team. An overview of this research project and a subset of results are presented in this poster.
Links Between Maternal Depressive Symptoms, Maternal Empathy, and Responses to Children’s Negative Emotions
(2021) Trujillo, Amanda; Deol, Gunleen; Straske, Davis; Fitter, Megan; Cassidy, Jude
The link between maternal depressive symptoms and negative socio-emotional child outcomes is well supported (e.g., Connell & Goodman, 2002; Dittrich et al., 2020; Goodman et al., 2011). However, prior research has not examined links between maternal empathy or mental health and mothers’ responses to child distress. The current study examines the association between maternal depressive symptoms and responses to children's negative emotions, with maternal empathy as a mediator. We hypothesize that mothers’ empathy will mediate the relation between maternal depressive symptoms and responses to children’s negative emotions, such that greater depressive symptoms will predict less empathy, which, in turn, will predict more unsupportive and fewer supportive responses to children’s negative emotions. Participants (N = 80) were mothers (47.6% white, 21.0% African American, 6.7% Asian/Pacific Islander, 10.5% Hispanic, 14.3% other and missing) and their children (M age = 4.5 years; 40.0% male, 49.5% female, 10.5% missing) from a two-part study with a 2-week interval between sessions. The indirect effects of maternal depressive symptoms on unsupportive responses (indirect effect = 0.001, [-.002, .004]) and supportive responses (indirect effect = .000, [-.002, .002]) through maternal empathy were not significant. However, there was a significant direct effect of maternal depressive symptoms on unsupportive responses (b = .028, p = .002) and a marginally significant direct effect of maternal depression on supportive responses (b = -.014, p = .089). Although we did not find a link between depressive symptoms and empathy, we found links between empathy and two subscales of unsupportive responses (maternal distress and punitive responses), and a marginally significant link between empathy and a subscale of supportive responses (problem-focused reactions). These findings suggest that parenting interventions targeting mothers with elevated depressive symptoms should aim to enhance maternal empathy to decrease unsupportive responses and increase supportive responses to children’s negative emotions.
Hawaiian Spinner Dolphins: Vulnerability to Climate Change and Exposure to Anthropogenic Sound
(2021) Panday, Frances Marie; Lettrich, Matthew
Cetaceans such as the Hawaiian spinner dolphin (Stenella longirostris) use the high-frequency (kHz) channel to communicate, find prey, and avoid predators. Anthropogenic activities, such as navigational sonar and vessel noise may result in acoustic disturbance or injury and impede dolphin behavior or have population-level impacts. Despite vessels producing lower frequency sounds (<400 Hz) that are detected at longer distances, it is still an effective proxy for sound propagation because higher frequency sounds are detected at shorter distances. This could mean overlap between vessel noise and dolphin hearing sensitivity, suggesting interference with their acoustic habitat. Climate change may also present additional threats to the distribution and abundance of the population. I evaluated the climate vulnerability and exposure to sound for two Hawaiian Spinner Dolphin stocks to determine if one stock was more at risk than the other and if there were any factors that contributed to such difference. I used NOAA Fisheries’ stock assessment reports to define clear stock boundaries and identify the pelagic and insular stocks. I conducted a literature review of relevant life histories and used a systematic methodology developed as part of NOAA Fisheries’ Marine Mammal Climate Vulnerability Assessment (MMCVA) project to assess their vulnerability to climate change. I quantified potential shipping exposure using a defined scoring rubric comparing the proportion of Marine Cadastre’s 2019 AIS (Automatic Identification Systems) Vessel Transit Counts data layer overlapping each stock boundary. Despite both stocks having high vulnerability to climate change, the insular stock was more susceptible due to the greater number of cumulative stressors and closer proximity to human activity. This stock also had greater exposure to sound because of its larger overlap with high-density vessel traffic. The life history attributes scored for climate change that have the most influence from sound were site fidelity, home range, and diet specificity. While the relationship between climate change and sound is still understudied, sound exposure may intensify the climate vulnerability of marine species if ocean acidification alters the ocean soundscape. Regardless, these findings offer resource managers additional information to consider in the management of Pacific cetacean stocks.
Using Nanoparticle Shape as a Parameter in Drug Delivery
(2021) Lee, Benjamin; Duncan, Gregg
Nanoparticle drug delivery systems encounter many biological barriers, such as mucus gels and the extracellular matrix, that they must bypass in order to gain access to target cells. With this, there is a need to design drug delivery systems to overcome these obstacles to increase their efficacy and retention. One parameter that has recently been looked into is nanoparticle shape, as due to their anisotropic shape, they will experience a drag force along the longer axis, giving them preferential motion along that direction, and higher diffusion and penetration through biological gels. This phenomenon has been demonstrated in gastrointestinal mucus, but the optimal dimensions and aspect ratio of nanoparticles to enhance this effect has yet to be established. To systematically approach this, fluorescent carboxyl-coated polystyrene rod-shaped nanoparticles were synthesized by stretching 100 nm, 200 nm, and 500 nm spherical nanoparticles. Transmission electron microscopy showed that the procedure yielded a combination of rods and spheres then separated by shape via centrifugation. Fluorescent microscopy and multiple particle tracking analysis was then used to characterize rod-shaped and spherical nanoparticle diffusion. In water, rod-shaped particles for all sizes exhibited lower diffusion rate, but when dispersed in MaxGel, an extracellular matrix-based hydrogel, rod shaped nanoparticles exhibit higher diffusion rate. These results would suggest that nanorods can better penetrate biological hydrogels, and thus would have a higher retention and efficacy than comparably-sized nanospheres. The results of this work establish the importance of shape in the design of nanomedicine.
Bystanders' Perceptions of Police-Civilian Conflict
(2021) Graninger, Alexandra M.; Tomlinson, Tracy D.
Nearly every human being automatically notices and remembers the race of each individual they encounter (Cosmides et al., 2003). Not only is race something that humans are often very attentive to, but it is also something that can affect perceptions of conflict, particularly between police and civilians (Weitzer & Tuch, 1999). Yet, very little research has been done specifically on bystanders’ perceptions of nonviolent conflicts with regard to race. The current study intended to partially fill the gap in the current literature by exploring bystanders’ perceptions of police-civilian nonviolent conflict. Specifically, how does the race of the police officer and race of the civilian impact bystanders’ perceptions of the conflict? In this study, race of the police officer and civilian were manipulated by giving participants slightly different variations of vignettes. The storyline of the vignettes was the same; the only difference between vignettes were the races (Black, White or race not mentioned) of the parties involved. We hypothesized that both changing the race of the police officer and changing the race of the civilian involved in the conflict would affect bystanders’ perceptions of the conflict; however, it is unclear how bystanders’ perceptions may change, based on some discrepancies in current literature (Orbe & Warren, 2000; Weitzer, 1999). We found that participants tended to rate conflicts involving a Black police officer as being more the civilian’s fault, as compared to when the police officer was either White or of unmentioned race, which provides important novel information as to how race can affect perceptions of conflict.
I’m sorry, curry & rice are just not my thing: Online sexual racism as a predictor of body-oriented concerns among East Asian and South Asian sexual minority men
(2021) Dua, Vardaan; Mohr, Jonathan
Nanoparticle-Mediated Delivery of Antioxidants for Improving the Survival of Beta Cell Implants for Treating Type 1 Diabetes
(2021-04) Kraus, Samantha; He, Xiaoming
Type 1 diabetes mellitus, an autoimmune disorder that destroys insulin-producing beta cells of the pancreas, poses a substantial monetary and clinical burden. A promising curative, noninvasive treatment of type I diabetes is pancreatic islet transplantation from a healthy donor to the afflicted recipient. However, transplantation stressors in the immediate post-isolation period, especially hypoxic stress, contribute to more than half of islet cell death within hours to days, limiting therapeutic restoration of normoglycemia. Recent studies on the cytoprotective effects of antioxidant-laden nanoparticles for survival and preservation of insulin secretion in pancreatic beta cells have demonstrated that two candidate antioxidants, bilirubin and quercetin, can significantly increase beta cell viability under hypoxic stress, as quercetin stimulates the heme oxygenase-1 pathways and stabilizes bilirubin levels. Therefore, this study aims to formulate PLGA-PF-127 polymeric nanoparticles surface-coated with chitosan for encapsulation and delivery of both bilirubin and quercetin to beta cells to increase cell survival under hypoxic stress, under the hypothesis that bilirubin and quercetin nanoparticles potentiate greater beta cell survival and protection of insulin secretion than either nanoparticle alone in a synergistic effect. Nanoparticles were formulated by a single emulsion method and subject to characterization. Cellular uptake of nanoparticle-encapsulated bilirubin was compared to free bilirubin in an insulinoma cell line (TC-6) model using confocal fluorescence microscopy. Finally, the model TC-6 cells were treated with concentrations of 0 to 40 μM of bilirubin and/or quercetin in nanoparticles or free drug form prior to incubation in hypoxic conditions, after which cell viability was assessed. Both types of nanoparticles presented an encapsulation efficiency of approximately 25% with a diameter of ~200 nm and less than 0.1 polydispersity. Confocal fluorescence imaging showed greater uptake of nanoparticle bilirubin into the TC-6 cells compared to free drug. The combination of nanoparticle bilirubin and quercetin at the dose of 40 μM increased the viability (40.7 ± 12.8% of control; p = 0.11) of TC-6 cells challenged by hypoxic stress, compared to untreated control cells. Thus, co-delivery of bilirubin and quercetin polymeric nanoparticles improves uptake compared to free drug and has the potential to increase islet survival under hypoxia.
Data Driven Methods to Balance Fairness and Profit in Ride-Pooling
(2021-04) Raman, Naveen; Dickerson, John
Rideshare and ride-pooling platforms use artificial intelligence-based matching algorithms to pair riders and drivers. However, these platforms can induce inequality either through an unequal income distribution or disparate treatment of riders. We investigate two methods to reduce forms of inequality in ride-pooling platforms: (1) incorporating fairness constraints into the objective function and (2) redistributing income to drivers to reduce income fluctuation and inequality. To evaluate our solutions, we use the New York City taxi data set. For the first method, we find that optimizing for driver-side fairness outperforms state-of-the-art models on the number of riders serviced, both in the worst-off neighborhood and overall, showing that optimizing for fairness can assist profitability in certain circumstances. For the second method, we explore income redistribution as a way to combat income inequality by having drivers keep an r-fraction of their income, and contributing the rest to a redistribution pool. For certain values of r, most drivers earn near their Shapley value, while still incentivizing drivers to maximize value, thereby avoiding the free-rider problem while reducing income variability.
Nanoparticle-Mediated Delivery of Antioxidants for Improving the Survival of Beta Cell Implants for Treating Type 1 Diabetes
(2021-04) Kraus, Samantha; He, Xiaoming
Type 1 diabetes mellitus, an autoimmune disorder that destroys insulin-producing beta cells of the pancreas, poses a substantial monetary and clinical burden. A promising curative, noninvasive treatment of type I diabetes is pancreatic islet transplantation from a healthy donor to the afflicted recipient. However, transplantation stressors in the immediate post-isolation period, especially hypoxic stress, contribute to more than half of islet cell death within hours to days, limiting therapeutic restoration of normoglycemia. Recent studies on the cytoprotective effects of antioxidant-laden nanoparticles for survival and preservation of insulin secretion in pancreatic beta cells have demonstrated that two candidate antioxidants, bilirubin and quercetin, can significantly increase beta cell viability under hypoxic stress, as quercetin stimulates the heme oxygenase-1 pathways and stabilizes bilirubin levels. Therefore, this study aims to formulate PLGA-PF-127 polymeric nanoparticles surface-coated with chitosan for encapsulation and delivery of both bilirubin and quercetin to beta cells to increase cell survival under hypoxic stress, under the hypothesis that bilirubin and quercetin nanoparticles potentiate greater beta cell survival and protection of insulin secretion than either nanoparticle alone in a synergistic effect. Nanoparticles were formulated by a single emulsion method and subject to characterization. Cellular uptake of nanoparticle-encapsulated bilirubin was compared to free bilirubin in an insulinoma cell line (TC-6) model using confocal fluorescence microscopy. Finally, the model TC-6 cells were treated with concentrations of 0 to 40 μM of bilirubin and/or quercetin in nanoparticles or free drug form prior to incubation in hypoxic conditions, after which cell viability was assessed. Both types of nanoparticles presented an encapsulation efficiency of approximately 25% with a diameter of ~200 nm and less than 0.1 polydispersity. Confocal fluorescence imaging showed greater uptake of nanoparticle bilirubin into the TC-6 cells compared to free drug. The combination of nanoparticle bilirubin and quercetin at the dose of 40 μM increased the viability (40.7 ± 12.8% of control; p = 0.11) of TC-6 cells challenged by hypoxic stress, compared to untreated control cells. Thus, co-delivery of bilirubin and quercetin polymeric nanoparticles improves uptake compared to free drug and has the potential to increase islet survival under hypoxia.
The JAK2-V617F Mutation Destabilizes a Programmed -1 Ribosomal Frameshift Signal
(2021-04) Tu, Kevin; Dinman, Jonathan
Programmed -1 ribosomal frameshifting (-1 PRF) is a translational recoding mechanism in which cis-acting elements direct elongating ribosomes to slip in the 5’ direction on mRNAs by one base. -1 PRF activity is able to downregulate gene expression by directing elongating ribosomes to premature termination codons, activating the nonsense-mediated decay pathway (NMD) and mRNA degradation. Computational methods developed by our lab identified a -1 PRF signal within the Janus Kinase 2 (JAK2) mRNA, which encodes a tyrosine kinase involved in cell proliferation, survival, and apoptosis. Here, we characterize the JAK2 -1 PRF signal. In addition, we show that the JAK2-V617F mutation, closely linked to myeloproliferative neoplasms (MPN), decreases JAK2 mediated frameshifting. This may contribute to the observed increase of JAK2 mRNA levels in MPN patient microarray and RNAseq data. Because it has been established that elevated expression levels of JAK proteins are sufficient to transform cells in vitro, our findings suggest that this may contribute to the observed increase in JAK2 kinase activity in mutant cells and thus the transforming activity of the V617F mutation. Our study offers a possible translational-level mechanism behind the development of MPNs, opening the door to new therapies for MPN patients.
Characterizing a Chimera: Comparative Analysis of Pal Endolysin and its Homologs
(2021-04) Griffin, Ryleigh; Lee, Harrison; O'Hara, Jessica; Nelson, Daniel
Once a virus infects a cell and produces more virus particles (virions), it must find a way to release those virions so they can infect more cells. Bacteriophage, or viruses that infect bacteria, accomplish this goal by producing endolysins, proteins that cause bacterial cells to lyse by breaking down their cell walls. Many endolysins have a modular structure consisting of an enzymatically active domain (EAD), which catalytically breaks bonds in peptidoglycan, the main component of bacterial cell walls, and a cell wall binding domain (CBD), which attaches the endolysin to the cell wall and determines host specificity. By combining EADs and CBDs from different endolysins, researchers can produce new “chimeric” endolysins in order to kill disease-causing bacteria in a targeted fashion, which can be more effective than the original enzymes. Chimeric endolysins can also form naturally. Bacteriophage Dp-1, which infects Streptococcus pneumoniae bacteria, produces a chimeric endolysin called Pal. Pal’s CBD has the ability to bind to choline and is very similar to a portion of the LytA enzyme produced by S. pneumoniae. Pal’s EAD breaks down amide bonds in peptidoglycan and is very similar to a portion of the endolysin produced by a Bacteriophage BK5-T, which infects Lactococcus lactis bacteria. In our research, we used bioinformatics techniques to find other proteins that share homology with Pal and to investigate the evolutionary relationships between these proteins. We hope that a better understanding of this natural chimeric endolysin could be useful to researchers attempting to engineer new ones.