Understanding the Relationship Between Ecdysone Signaling and the Lipin Protein in Drosophila melanogaster

Drosophila melanogaster, the common fruit fly, undergoes four major stages of development: embryonic stage, larval stage, pupal stage, and adult stage. During the larval stage, individuals increase in size and consume nutrients, which are then stored in the cells of the fat body. When the larva reaches critical weight, the formation of the pupal case or pupariation occurs over four days and undergoes a transformation from its larval form to its adult form. During these four days, the pupa will not consume any external nutrients and is reliant on the nutrients stored in the cells of the fat body as a result. The pupal stage is an energetically expensive process. In Drosophila, there is a single lipin gene orthologue known as dLipin. Lipin is a protein that is encoded by the lipin gene. Lipin is considered essential for normal adipose tissue development and triacylglycerol (TAG) storage. dLipin is linked to energy metabolism and is considered to be crucial under nutrient deprivation conditions. dLipin also plays a role in insulin sensitivity in the larval fat body (Lehmann, 2018). Ecdysone is a steroid hormone that acts through a receptor to regulate the transcription of specific target genes. This steroid hormone is the central regulator of developmental transitions in Drosophila and leads to pupariation at the beginning of metamorphosis. I hypothesize that ecdysone signaling activates the transcription of the dLipin gene during metamorphosis. To test this hypothesis, I am using the wild-type genotype as a control, and Cg-Gal4; UAS-EcR-DN flies as an ecdysone-signaling-deficient experimental genotype. Results of the Real-Time Quantitative Polymerase Chain Reaction (qRT-PCR) indicate the opposite of the hypothesis and that ecdysone signaling instead inhibits the transcription of the dLipin gene. Ecdysone deficient Drosophila resulted in up-regulation of dLipin compared to the wild-type Drosophila. Studying lipin in the Drosophila model will help lead to an understanding of the basic function of lipin in metazoans and lipin’s role in fat cell function and energy metabolism (Schmitt, 2015).Biological Science

The Impact of Sex and Aging on Heat Shock Protein Induction in a Drosophila melanogaster Model of Glial Tauopathy

Tauopathies are a family of neurodegenerative diseases, which include Alzheimer’s disease, frontotemporal lobe dementia, and progressive supranuclear palsy. This subclass of diseases is characterized by the aggregation of hyperphosphorylated tau in neurons and glia. Heat shock chaperone proteins (HSPs) are able to help maintain proteostasis by helping to monitor protein synthesis, folding, trafficking, assembly of quaternary structures, turnover, and clearance of toxic aggregates. However, these protective mechanisms are insufficient when responding to tau proteotoxicity. Further complicating the matter, many neurodegenerative diseases present sexual dimorphisms in their onset, progression, and severity. Additionally, studies have shown that certain HSPs can become overwhelmed by stress as the system ages, which in turn causes a decline in the global defense mechanism. As a result, this study seeks to uncover how glial tau aggregation, age, and sex concurrently impact the chaperone system by performing a holistic screening of HSP induction in a Drosophila melanogaster model. Our studies highlighted how each heat shock chaperone uniquely contributes to the proteostasis machinery. Responses to our experimental variables vary greatly across this protein family. Female flies seem to respond more globally to heat shock by itself or in combination with glial tau or aging stress. Male flies exhibit stronger responses to the simultaneous combination of all three stresses. Basal suppression of HSP27 and the age-dependency of HSP70 and HSP27’s upregulation in response to tau in females may indicate a predisposition towards disease, as these are crucial HSP pathways in glial cells. Further investigation into the causes of these sex-related differences is warranted to unravel the mechanisms behind the chaperone response to glial tau.Biochemistr

Synthesizing Reactive Oxygen Species Sensitive Drug Delivery Vehicles

Drug delivery vehicles can be designed to provide a more efficient and effective tactic for delivering therapeutic payloads to their sites of activity by protecting their cargo until degradation conditions are met. Because of the association between high concentrations of reactive oxygen species with a variety of inflammatory diseases, the reactive oxygen species superoxide and hydrogen peroxide are appealing targets for payload release. The compound trifluoromethyl sulfonate has been found to degrade in the presence of superoxide (Chen, et al. 2019). Modification of dextran polymer with trifluoromethyl sulfonate is expected to confer hydrophobicity to the polymeric material and exposure to superoxide reverts it back to a hydrophilic material. The hydrophobic-modified dextran will form nanoparticles upon precipitation into an aqueous solvent. However, characterization by proton NMR and apparent solubility suggests that improvements need to be made in future synthesis, as the modification was unsuccessful. Boronic esters have been widely used to trigger degradation in the presence of hydrogen peroxide, and pinacol is an especially common esterifying diol used (Broaders, et al. 2011). Recent studies have found that dextran polymer-based delivery vehicles modified with pinanediol, a rigid diol, are more stable and soluble in organic solvents than their pinacol counterparts (Manaster, et al. 2019). Pinacol delivery vehicles (Pin-B Dex) can be made multifunctional through the addition of diols conjugated to therapeutic or fluorescent molecules via boronic ester transesterification reactions. Pinacol was successfully added to dextran, confirmed by H-NMR, and addition of pinanediol confirmed that Pin-B-Dex can be modified. In order to add more functional modifications, fluorescence, or therapeutic molecules, the modification molecule of choice will be attached to nopol diol enabling its addition onto Pin-B Dex. One such modification was synthesized through the addition of pyrenebutyric acid, a fluorescent molecule, onto nopol diol. Pin-B-Dex was successfully modified according to H-NMR; however, the small yield of the product suggests that improvements could be made in future syntheses.Biochemistr

Memory Deficits and Cytokines in the Hippocampus in a Rat Model of ADHD

Attention deficit hyperactivity disorder (ADHD) is a complex behavioral disorder characterized by hyperactivity, impulsivity, inattention, and deficits in working memory and time perception. While animal models have contributed to our neurobiological understanding of this condition, there are limited and inconsistent data on working memory and memory for time deficits. Inflammatory signaling has been identified as a key factor in memory and cognitive impairments, but its role in ADHD remains unclear. Additionally, the disproportionate investigation of male subjects in ADHD research has contributed to a poor understanding of the disorder in females. This study sought to investigate the potential connections between memory, neuroimmunology, and ADHD in animals of both sexes. Specifically, we utilized the spontaneously hypertensive rat (SHR), one of the most extensively studied animal models of ADHD. Compared to their control, the Wistar-Kyoto (WKY) rats, male SHR have been previously reported to exhibit several behavioral phenotypes associated with ADHD, including hyperactivity, impulsivity, and poor sustained attention, along with impairments in learning and memory. As the hippocampus is a key brain region for learning and memory, we examined the behavior of male and female SHR and WKY rats in multiple hippocampal-dependent memory tasks. Our findings revealed that SHR had delay-dependent working memory deficits that were similar to, albeit less severe than, those seen in hippocampal-lesioned rats. We also observed impairments in elapsed time processing in female SHR, particularly in longer time durations. To investigate the impact of inflammatory signaling on memory in these rats, we analyzed the levels of several cytokines in the dorsal and ventral hippocampus of SHR and WKY. Though we found some sex and genotype differences, concentrations were generally similar between groups. Taken together, our results indicate that SHR exhibit deficits in spatial working memory and memory for time, as well as some differences in hippocampal cytokine concentrations. These findings contribute to a better understanding of the neurobiological basis of ADHD and may inform future research aimed at developing effective treatments for the disorder. Nonetheless, the potential mediating role of neuroinflammation in the memory symptomatology of SHR requires further investigation.Neuroscience and Behavio

Witches, Devils, Madonnas, and Fairies: Tradition and Innovation in Verdi’s Adaptations of Shakespeare

William Shakespeare is one of the most adapted playwrights of all time; film, stage, and musical adaptations abound since the late seventeenth century. In the world of music, art songs, ballets, operas, musicals, symphonies, vaudeville, and more have been inspired by the works of Shakespeare; in addition to composers creating incidental music for the plays themselves. Of the Shakespeare-inspired operas, perhaps the most famous are those of Giuseppe Verdi: Macbeth (1847), Otello (1887), and Falstaff (1893). In this thesis, I explore the overall effect of each of Verdi’s Shakespeare operas through the way in which he and his librettists develop major characters and emphasize thematic elements. I discuss the production history of each of the plays these operas were based on, making connections between standard performance practice and the way that the characters are depicted in Verdi’s operas. In addition, I address not only operatic tradition and how these conventions shaped Verdi’s adaptations, but also how Verdi’s operas pushed back against these conventions, creating a new style of opera. Music’s role in conveying a story has shifted throughout opera’s history. From opera’s first emergence, music was generally the most important aspect of performance—often treated as more important than story. Although structures shifted over the next century, the emphasis on music remained. Prima donna and virtuoso culture allowed the singers more prerogative in changing a composer’s score, often to include more embellishments or impressive notes. Verdi had to contend with the power of individual singers and impresarios throughout the beginning of his career, but was soon able to gain enough power himself to put the story first. Although Verdi’s operas are often considered among the most faithful to Shakespeare’s original works, he had to reconcile operatic convention with the innovations that Shakespeare's plots require. Because he did not speak English, Verdi was also relying on translations of these plays rather than the originals themselves; the difference in languages combined with artistic liberties on the part of the translator may alter a reader’s understanding of these translations. As a result, the Verdian versions of Shakespeare’s characters differ from their original counterparts. I will be looking closely at a number of these characters—Macbeth, Lady Macbeth and the Witches; Desdemona and Iago; and Falstaff and the Merry Wives—in an attempt to analyze what elements of the characters were altered in translation while also acknowledging the dimensions gained. A key element that has emerged throughout my discussion of the three operas is the way in which the female characters in Verdi’s operas are given power they do not have in the plays through their supernatural connections.Theatre Art

Studying inflated calyx syndrome in Physalis grisea

Physalis grisea, also known as groundcherry, is a member of the Solanaceae family and possesses a striking morphological novelty called inflated calyx syndrome (ICS). The inflated calyx is a modified version of sepals, which transform into a balloon-like husk that encases the fruit after the flower is fertilized. Because the genetic underpinnings of this trait remain unclear, the purpose of my project was to understand the genes controlling ICS in P. grisea. I focused on four homeotic genes from the MADS-box family, each one regulating an aspect of floral organ development. These genes are MPF3, DEF, TAG1, and EJ2, and previous research in other members of Physalis and the Solanaceae suggests that they are implicated in ICS development. I analyzed the floral morphology and genome sequences of four P. grisea CRISPR-edited mutant lines, each of which had one of the four genes of interest had been knocked out. My findings indicate that MPF3, TAG1, and EJ2 each affect ICS differently: mpf3 led to stunted inflated calyces; tag1 was correlated with a lack of calyx inflation, likely due to male infertility from the transformation of stamens into petaloid organs; and ej2 disrupted ICS development by altering sepal identity and number.Biological Science

JAPANESE REPRODUCTIVE HEALTH: SPACE AND OPPORTUNITY FOR REPRODUCTIVE HEALTH TALK AND THE ROLE OF WOMEN’S COLLEGES

This project examines Japanese college students’ experiences with reproductive health care and information access in Japan. I engage with participants’ stories to understand the complexity of the issues around sexual and reproductive health rights in Japan, identify the barriers to accessing care and knowledge, and learn how they overcome the barriers with constraints. Each participant offers their perspectives on reproductive health and experience as a person who lives in Japan, who attends a women’s college, and who is in their early twenties in this project. I use a feminist methodological approach, Interpretive Phenomenological Approach, and feminist usage of Foucault’s theoretical framework of biopower/biopolitics to analyze and deeply engage with the participant’s embodied knowledge. With an interdisciplinary approach, I focus on the participant’s own interpretation of their experiences and of the world they live in. Additionally, I interpret what participants are noticing about how complex social structures, norms, policies, and interpersonal relationships intersect with women’s experiences with reproductive health in Japan. Participants shared their stories within the category of visible, invisible, and shifting reproductive health topics. Visible topics are the focus of society for resolution as well as a heightened focus on gender discrimination. On the other hand, invisible topics are not often talked about in public spaces and women’s embodied experiences are kept silent as they are sources of stigma, discomfort, and discrimination. Lastly, shifting topics can appear or disappear in certain spaces and in contexts. Through this project, it is identified that Japanese women, who are mainly the center of the reproductive health discourse, are not noticing themselves as articulating their thoughts within the framework of reproductive health. With social norms, stigmas, and political ideologies that often discourage women from having conversations about their bodies and health, I suggest that women’s colleges have the possibilities as a space for women to feel empowered, build self-efficacy and self-affirmation, gain knowledge and skills to confidently exchange their thoughts and experiences with reproductive health in Japan, which then leads to the promotion of reproductive health care and information access.Gender Studie

Simulating flow behavior of soft particles in a quasi-two-dimensional silo under varying gravity

Systems as diverse as sand, crowds of people, and the rings of Saturn can be classified as granular materials. Omnipresent in our daily lives, in nearly every field of science, and part of billions of dollars per year in industry, we know surprisingly little about how granular materials behave. For systems such as gases we can take the understanding that atoms will bounce off of each other and the walls and derive the Ideal Gas Law. No such local behavior to bulk behavior scaling exists for granular materials. Due to factors discussed within such as unequal force distribution, there is a mid-“meso-scale" present that disrupts our ability to predict bulk behavior. As a result, granular systems can behave both in a liquid-like manner when they flow or a solid-like manner when they jam. In this thesis, we study the specific geometry of a silo, which can be simply conceptualized as a container, filled with a granular material, that has a outlet (aperture) in the bottom – thus allowing the grains to flow out under the force of gravity. This ostensibly simple system is reasonably well described by an equation called the Beverloo equation, but only for typical systems: hard particles at regular Earth gravity (9.81m/s2). Understanding how systems of soft particles flow is important for building a comprehensive model of granular flow and for applications in fields such as biology. Understanding how granular materials behave in different gravity is essential for space exploration and extra- planetary science. For example, if we want to land a spacecraft on an asteroid that has its own microgravity, we need to understand how the grains that make up the surface of that asteroid will behave in a system very different to what we have on Earth. In order to study these questions, we use molecular dynamics (MD) simulations through the software LAMMPS (Large Atomic/Molecular Massively Parallel Simulator). This software uses Newton’s law of motion and a model of particle contact to output position, velocity, and force data for each particle at every timestep. Simulating our system allows us to easily vary particle stiffness, gravity, and the diameter of the aperture. We study a quasi-two-dimensional system made up of a single vertical layer of spheres. We present our results on local measurements such as granular temperature, mesoscale measurements such as velocity profiles, and bulk measurements such as flow rate. We also discuss pressure waves that we observed within our system. We present a hypothesis for a relationship between granular temperature and deviation from the Beverloo equation. We also observe that a dimensionless ratio of gravity and stiffness, Γ, collapses many of our measurements and reveals trends.Physic

Beyond the Boundaries: Depicting Multiracial and Queer Identities in And/Or

This thesis was for a major called Mixed Media Storytelling (Creative Writing, Film, Music, and Theatre)This is a senior thesis film (accompanied by a thesis paper) about the intersectionality of being multiracial and queer. The film follows a queer, multiracial girl named Diya as she attempts to explore her sexuality while reckoning with her South Asian heritage, and ultimately learns that she can cherish her multiraciality and queerness at the same time without having to choose one. This film should speak to other multiracial, queer, and multiracial & queer individuals like myself who feel that we deserve more representation in media, and the chance to advocate for our beautiful and multifaceted identities.Other or Special Majo

Using Data Provenance to Support Reproducibility in R

The use of computers for data processing and analysis has dramatically transformed the approaches and capabilities of scientific research. Today, researchers are able to process and draw conclusions from large volumes of data in relatively little time, expanding the breadth and efficiency of their work. Despite this shift, verifying results through multiple studies and experiments will always remain important. A 2019 National Academies report recommended more research and development to ensure published scientific results are computationally reproducible, meaning the same results can be derived from the original data and analysis methods. Often, computational reproducibility requires information about the computing environment – such as the operating system, language, and package versions where the results were produced – as well as the data and script. This is because software can behave differently when components of the computing environment change. Therefore, an approach to reproducible research involves collecting all of the information about the scripts, data, and computing environment, also known as data provenance. In the R language, the rdtLite package facilitates the collection of data provenance for a given script execution. This thesis will focus on developing methods that use data provenance as a blueprint for reconstructing a computing environment and conducting experiments that apply this tool to identify situations in which changes to the environment resulted in changes in script behavior.Computer Scienc