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Dissecting Human and Influenza Virus Interaction with qFRET Technology

Influenza viruses cause seasonal epidemics and occasional pandemics around the world. During each flu season, IAV and IBV viruses are circulated widely in the community, with IAV being the dominant circulating virus and IBV accounting for 25% of all flu cases on average. Due to the significant threat posed by the flu virus, international organizations, including the World Health Organization (WHO), have risen to prominence in limiting its global effect. Despite the vaccinations and anti-flu medications that have been develop to combat influenza, drug resistance development highlights the necessity of further studies for influenzas virus pathogenesis and new therapeutic development. Förster resonance energy transfer (FRET) is a technique for detecting protein interactions in vitro and in vivo that is widely employed in biological and biomedical research. Here we report that the IBV M1 protein has a high affinity with human SUMOylation enzymes, the conjugating enzyme UBC9 and the ligase PIAS1, and conform M1 can be SUMOylated determined with a quantitative FRET (qFRET) assay developed in our lab. Understanding the viral infection process and developing new treatment methods requires identifying and deciphering the host route of viral infection. It is critical to comprehend the viral infection process and develop new therapeutics. Blocking the host human SUMOylation pathway is particularly effective for IBV reduction. Our research provides a direct interaction of human proteins with influenza B protein, providing new insights in human-virus interactions for future therapeutics development.

Has Anybody Asked How People Change Their Minds? Pre-crastination and Its Underlying Basis in Decision-Making

Procrastination is much too familiar to us, a derogatory term taught to students as something to avoid, which, to teachers’ despair, counterproductively encourages students to take up procrastination as a challenge. The opposite of procrastination, pre-crastination describes the likelihood of completing tasks early at the expense of extra effort, and may be a phenomenon as common as procrastination (Rosenbaum et al., 2014). We hypothesize that fundamentally, pre-crastination is cognitively driven, given that participants offload cognitive tasks before determining the course of action. This study took place over three experiments. Our pool of UCR undergraduate participants (N=89) made two forced yes/no responses pertaining to the same stimulus in each trial. The stimuli in the first experiment was determining chronology of number sequences while the stimuli in the subsequent two experiments was determining digit-matching. The most significant alteration was made in the third experiment, in which the second response was changed from a yes/no to a confirm/disconfirm submission. This innovative testing strategy, coined double-response in our lab, allows us to correlate response time to decision-making bases. Largely, participants exhibited a significantly longer reaction time in submitting their first response. This outcome supports our cognitive hypothesis which predicts that action-planning occurs through longer first-response times, going against the behavioral hypothesis which predicts that action is taken prematurely through shorter first-response times. Ultimately, this double-response method better helps us understand the dynamics of decision-making through pre-crastination.

Evaluating Poly(anhydride-ester) Encapsulation Characteristics for Delivery of Hydrophobic Small Molecules

Biodegradable salicylic acid-based poly(anhydride-ester)s (SAPAE) have proven to be effective in many biomedical applications including controlling inflammation, promoting bone growth, and preventing biofilm formation due to the release of salicylic acid upon hydrolysis of the polymer anhydride and ester bonds. Microspheres of SAPAE polymer are one fabrication option available for the encapsulation and controlled release of hydrophobic small molecules. This project aims to evaluate and characterize the ability for SAPAE microspheres to encapsulate, protect, and deliver retinol, a small hydrophobic molecule which is highly used in dermatological and cosmetic products for anti-aging purposes. The SAPAE of interest is a copolymer of salicylic acid (SA), adipic acid, and a diphenylene acetic acid (PAA). Due to supply chain limitations, the polymers used to form microspheres were of two variations, low molecular weight and high molecular weight. Nonetheless, this allowed for comparison of microspheres characteristics including size, morphology, and retinol loading efficiency. Through scanning electron microscopy (SEM), it was confirmed that the unloaded and retinol-loaded microspheres had a spherical shape, and the sizes were similar between the low molecular weight and high molecular weight polymer versions. Residual methylene chloride solvent was successfully reduced in all samples which increases the viability for biological applications. Finally, ultraviolet-visible spectroscopy detected a maximum of 4% w/v loading of retinol in the microspheres.

 

Transborder Realities: Its Effect on Bordertown Students Pursuing a Higher Education

In this research I dive into the testimonies of five border town students who live on the U.S.-Mexico border in the transborder community composed of sister-cities, Calexico, California, and Mexicali, Baja California Mexico. The goal of this study is to use testimonials to help us understand the flaws within the educational site of Calexico High school as well as the limitations it imposes on transborder border town students. Transborder Realities is a new type of journalism focusing on the stories of individuals as a way to bring forward the realities of many. This study unveils the intersectionality between social class, residency, and economic status that lead to social hierarchies in school, creating a division between students of different backgrounds. Each of the participants share personal experiences that greatly impacted them academically as transborder students, encounters that have not only led to struggles with their language, mental health, and career and educational endeavors, but also pushed them in search of better opportunities. This study brings to light the reality of being a transborder student in this culturally rich community, what that entails, and the effects it had in their pursuit of a higher education. These testimonials help to reveal the stigma faced within the educational community of Calexico in hopes of decreasing the mistreatment of transborder students pursuing higher education in the United States.

 

Effects of Parenthood on Neural Responses to Pup-Related Cues

The onset of parental care in female mammals is associated with plasticity in neural processing of infant-related sensory stimuli, which enhances mothers’ ability to detect and care for their offspring; however, little is known about sensory plasticity in fathers. We tested the hypothesis that parenthood alters neural responses to olfactory and auditory stimuli from infants in male and female California mice (Peromyscus californicus), a biparental rodent. Virgins and new parents of both sexes were exposed to a combination of a chemosensory stimulus (pup-scented or unscented cotton [control]) and an auditory stimulus (pup vocalizations or white noise [control]). Brains were collected one hour later and stained immunohistochemically for Fos, an index of neural activity. We quantified Fos in the main olfactory bulbs (MOB), a region essential to receiving olfactory information, and medial preoptic area (MPOA), a region critical for parental behavior. We predicted that Fos in MOB and MPOA would be greater in parents than virgins, especially after exposure to pup stimuli. We found that in females, MPOA and MOB Fos did not differ between virgins and mothers or across treatment groups. In contrast, fathers had lower expression of Fos in MOB but higher expression in MPOA, compared to virgin males. Moreover, Fos in MPOA was higher in males exposed to pup vocalizations and pup scent compared to those exposed exclusively to pup vocalizations. Fos in MPOA was also higher in males exposed to scent or both scent and vocalization stimuli compared to males exposed to control stimuli. These findings suggest that the onset of parenthood alters activity in the MOB and MPOA, especially in response to pup vocalizations and scents, in males but not females in this biparental rodent.

Sexualizing Señoritas: Portrayals of Mexican Women during World War I

The obstacles that white women had to face during WWI have been widely documented in books such as Elizabeth Cobbs’, Hello Girls and Diane North’s California at War: The State and People During World War I. However, less attention has been paid to the obstacles faced by Mexican women. My paper draws on newspaper articles, fictionalized accounts, and recent scholarly work to examine how Mexican women were portrayed in contrast to portrayals of white women during this period. The portrayal of Mexican women in the media as illiterate, ignorant, and in need of white saviors, reinforced the stereotype of a hypersexualized damsel in distress. These portrayals of Mexican women reflected existing racism, sexism, and classism by neglecting/diminishing their accomplishments. Recovering the contributions and lived experiences of Mexican American women during this time are crucial to understanding California history in World War I.

 

Evaluating Imatinib's Affinities and Specificities for Tyrosine Kinases Using Molecular Dynamics Simulations

Computational chemistry lets us model intermolecular interactions in ways assays cannot. My project focuses on the multi-kinase interactions of the cancer drug, imatinib. Most cancer drugs target one kinase, but some affect multiple kinases. Imatinib treats chronic myeloid leukemia by targeting ABL kinase. Proteomics data reveals it can interact with other kinases, such as KIT to treat gastrointestinal stromal tumors, but the mechanisms are unknown. Imatinib has different affinities for similar kinases, such as a 3000x difference between ABL and SRC, despite sharing 50% structural homology. Here, I investigate the conformational differences between free and imatinib-bound ABL, KIT, and SRC using Molecular Dynamics simulations to understand the key imatinib-kinase interactions. The alignment analysis shows the docked conformations are similar to co-crystal structures in the Protein Data Bank. Root-mean-square-deviation and fluctuation (RMSD and RMSF) analysis show that all simulations converge at 45 ns, with some regions exhibiting differential flexibility. Hydrogen bond analysis across 100 ns simulations show that ABL has one main H-bond, KIT has three main H-bonds, and SRC has no main H-bonds. All the drug-kinase complexes feature at least 15 key salt bridge interactions relevant for structural stability. The dihedral distributions reveal that most residues adopt a single conformation, but some can adopt multiple, increasing the protein flexibility. The entropy results quantify the protein disorder, revealing KIT and SRC favors the apoprotein while ABL favors the complex. This signifies that broad protein similarity does not govern imatinib binding, instead, it is explained by smaller structural details.