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In Vitro Modulation of IgE Response
No full textExposure to microbial products has been demonstrated to be inversely correlated to allergic conditions. Toll- like receptors sense microbial products and modulate immune responses. Our lab previously found that Toll-like receptor 9 signaling activated with microbial DNA mimicry reduced IgE production by decreasing germline transcription at the I-epsilon locus, a prerequisite for class switching. In this study, we investigate the direct effects and the mechanisms of activating other TLRs expressed on B cells on decreasing IgE class switching in vitro. To monitor class switching to IgE in mouse B cells, we use a reporter mouse strain that tracks I-epsilon germline transcription by the expression of a fluorescent protein. We stimulate mouse splenic B cells with anti-CD40 antibodies and IL-4 to drive class switching to IgE, and measure whether the addition of different TLR agonists reduces germline transcription. Additionally, we measure the expression of CD40 and IL-4 receptor on cultured cells to test if TLR agonists decrease cell responsiveness to these signals needed for class switching. We also investigate other mechanisms that may lead to decreased IgE production including plasma cell differentiation. Lastly, we adapt an in vitro human tonsil organoid system, stimulate the tonsil organoid with model protein antigens to induce antigen specific antibody responses. We aim to use this system to study the production of IgE as well as to test the effect of modulating TLR signaling in B cells on IgE response
American Rap Scenes: An Analysis of 25 Locations
No full textAmerican Rap Scenes examines the history and legacy of rap music in 25 American cities through factors of geography, migration, movements, music, and technology.Providing area-centered analysis of a culture many see as monolithic, Lavar Pope highlights the unique histories of rap music and Hip Hop culture - how and why these scenes developed - in 25 mid-size and major cities across the country. More so than other genres of music, rap offers historical record of a multigenerational Black music that is region- and locale- specific and opens a window into the Black experience in America. Highlighting global stars and key local artists alike, American Rap Scenes features artists contextualized within their city of origin from Andre 3000 (Atlanta), Kendrick Lamar (Compton), and Common (Chicago) to Too Short (Oakland), Freddie Gibbs (Gary), and Akon (Jersey City).The 25 scenes covered in this book are South Bronx, Manhattan and Harlem, Queens, Brooklyn, Staten Island, Hempstead, Philadelphia, Newark and Jersey City, Boston, Los Angeles and Compton, Oakland and the San Francisco Bay Area, Seattle and Portland, Chicago and Gary, Indiana, St. Louis, Minneapolis, Detroit, Houston, New Orleans, Memphis, Atlanta, Miami, Hampton, Virginia, Washington, D.C. and Baltimore, Honolulu, San Juan, Puerto Rico and Saint Thomas, USVI.These scenes have been chosen for the documented and longstanding histories of their local music-making communities as well as similarities in the evolution of the local environment and geography, the proximity and timeline of Black, Latinx, and Caribbean migrations, and the impact of the Civil Rights, Racial Justice, and Women\u27s Movements.https://ecommons.luc.edu/facultybooks/1288/thumbnail.jp
Trash Trap: Categorizing Plastic Pollution in Chicago\u27s Montrose Harbor
Full text linkPollution of aquatic ecosystems by trash, including plastic, is a critical environmental and public health issue. The input and abundance of plastic to the environment is increasing and is worsened by climate change. Plastic litter poses a direct threat to both human and wildlife health through ingestion and entanglement. In addition, plastic particles leach toxic chemicals as they break down in the environment, creating low-level and persistent pollutant exposures. Lakes and rivers in urban areas are critical sites of litter input because they are closely connected to litter sources. Lakes and rivers are key sources of litter to oceans, and are far lower in volume. Thus, urban lakes and rivers are critical sites for litter prevention and removal. The objective of this study was to determine the types of litter that enter a Lake Michigan marina in Chicago. Marine debris was collected over eight weeks from Montrose Harbor in a Marina Skimmer. This device is largely submerged underwater, and uses a pump to draw in water and floating trash into its 15 m3 container. Trash was removed from the device approximately weekly. In the lab, the trash was dried, sorted, categorized, and weighed. Results indicated that the most prevalent type of debris collected was plastic. By category, the main types of litter were fragments larger than 3 mm and food related trash. Future research on this topic can be used to inform public education campaigns and policies relating to the most prevalent litter types at the site
“Buying Time or Doing Harm?”: Tracing Contestation and Consensus in Debates on Puberty Blockers for Trans Youth
No full textThe use of hormone blockers and other forms of gender affirming medical care for trans youth has emerged as a site of medical and political contestation, with 26 states passing legislation outlawing their use (Movement Advancement Project, 2024). Drawing from a multiple-methods approach, this dissertation examines the ways in which this contestation emerged and has been framed both in political case law and digital spaces, which a specific attunement toward how medical discourse is used to support arguments calling for either the allowance or ban of hormone blockers. This dissertation highlights the ways in which the families of trans youth respond to and make sense of the legislative ban on hormone blockers. Chapter One of this dissertation uses content analysis and case comparison in order to highlight how legislative documents generated in Arkansas and Texas have used medical rhetoric to both ban and appeal the ban of hormone blockers and other forms of gender affirming care. In Chapter Two, content analysis is used to examine how digital communities have formed to call for either the allowance or ban of hormone blockers for trans youth. Chapter Three uses interview data to understand how parents of trans youth frame and understand the political contestation of hormone blockers, and how these bans impact their families. This research has significant implications for sociological scholarship, as it is one of the first works to consider the use of medical rhetoric within on-going debates on the use of hormone blockers. Further, this work contributes to the fields of science and technology studies through an examination of the politicization of science, as well as works within medical sociology studying trans health
Uncovering the Mechanisms of the Anti-Cancer Activity of New Non-Covalent Thioredoxin Reductase inhibitors in Triple Negative Breast Cancer
No full textTriple negative breast cancer (TNBC) makes up only 15-20% of all breast cancer cases, yet it contributes to almost 50% of all breast cancer related mortalities. This highlights the urgent need to develop novel therapeutics for the treatment of TNBC. The thioredoxin (Trx) system is an important cellular antioxidant pathway supported by the enzyme thioredoxin reductase 1, TXNRD1. Upon reduction by TXNRD1, Trx regulates many cellular functions including redox homeostasis and DNA replication and repair through ribonucleotide reductase (RNR), which catalyzes the rate limiting step in the de novo synthesis of dNTPs. Notably, TXNRD1 is elevated in TNBC, thus presents a druggable vulnerability. We identified novel non-covalent inhibitors, TXNRD(i)s, that bind to a unique allosteric site, the “doorstop pocket”, and have previously shown they exhibit anti-cancer activity in TNBC. This study focuses on characterizing the mechanisms of anti-cancer effects elicited by these inhibitors to guide future drug optimization and development in TNBC. To identify major pathways affected, we conducted transcriptomics in TNBC cells treated with two lead TXNRD(i)s or siTXNRD1. Bioinformatic analysis revealed enrichment of oxidative stress (ROS) along with multiple proliferation and cell cycle pathways. Although TXNRD(i) treatment increased intracellular ROS levels, this elevation did not correlate with reduced cell viability. Furthermore, treatment with antioxidant ROS scavengers failed to rescue the TXNRD(i)-induced effects, indicating that elevated ROS is not the primary driver of their cytotoxic activity. We next evaluated the impact of TXNRD(i)s on TNBC cell proliferation and observed a marked reduction in DNA synthesis, accompanied by G1 phase cell cycle arrest. Given that Trx supports ribonucleotide reductase (RNR) activity, we tested whether exogenous supplementation with dNTPs, the products of RNR, could reverse these effects. Indeed, dNTP supplementation fully rescued the cell cycle arrest and significantly restored cell viability while reducing apoptosis and DNA damage. These findings strongly support the conclusion that disruption of RNR function is the key mechanism underlying the anti-cancer effects of TXNRD(i)s in TNBC. Overall, our study challenges the prevailing view that TXNRD1 inhibitors primarily act through pro-oxidant mechanisms and instead highlights a critical role for the TXNRD-Trx-RNR axis in sustaining TNBC cell proliferation and survival
Polycystin-2 Is Cardioprotective Against Myocardial Infarction by Regulating the Calcium-Mediated Er-Stress Response
No full textPatients with autosomal polycystic kidney disease (ADPKD) have an increased risk and worse outcomes after acute myocardial infarction, but the mechanism for this is unknown. Polycystin 2 (PC2), one of the two main proteins mutated in ADPKD, is a calcium permeant channel that localizes to the ER/SR. In non-cardiac cells, PC2 regulates the unfolded protein response (UPR) pathway under ER stress. However, whether PC2 is cardioprotective against ER stress is unknown. We found that PC2 expression increased in cardiomyocytes from human ischemic hearts and infarcted murine hearts. Cardiomyocyte-specific PC2 KO (PC2 KO) mice had worsened cardiac function after myocardial infarction (MI) compared to control (CTL) mice. The UPR arm PERK and its downstream target CHOP were decreased in PC2 KO mice and myoblast PC2 KO cells. The ER stress activator tunicamycin increased ER calcium leak and mitochondrial calcium in CTL cells, but not in PC2 KO cells or isolated PC2 KO cardiomyocytes. Consequently, there was impaired mitochondrial membrane potential and increased cell death in PC2 KO cells. Tunicamycin induced a rapid increase in PC2 expression with enhanced localization to ER-mitochondrial contact sites. Importantly, restoration of functional PC2 in vitro enhanced PERK phosphorylation and the calcium leak in PC2 KO cells. These data suggest that the upregulation of PC2 with ER stress facilitates its function as a leak channel under ER stress, regulating UPR-mitochondrial crosstalk in the early adaptive phase of ER stress. Loss of PC2 impairs the early adaptation and results in worsened cardiac dysfunction with AMI
Discerning the Role of Microtubule Acetylation During HIV-1 Infection
Full text linkThe host-pathogen interactions underlying Human Immunodeficiency Virus type 1 (HIV-1) infection are complex and involve the exploitation of host cellular machinery. This thesis investigates the roles of dynein adaptors, microtubule acetylation, and TRIM69-mediated restriction in HIV-1 infection. Through a series of detailed experiments, we explore how HIV-1 utilizes multiple dynein adaptors, such as BICDR1 and Hook3, for intracellular transport, and reveal that these adaptors are critical for efficient viral trafficking. Conversely, the knockdown of Ninein surprisingly enhances HIV-1 infectivity, suggesting a nuanced regulatory role for this adaptor in viral transport. Further, this thesis challenges the prevailing paradigm that microtubule acetylation is essential for HIV-1 infection. Using CRISPR-Cas9 technology to knock out the αTAT1 enzyme responsible for microtubule acetylation, and overexpressing an αTAT1-mCherry construct, we demonstrate that HIV-1 can replicate effectively without microtubule acetylation. This finding prompts a re-evaluation of the role of microtubule modifications in HIV-1 pathogenesis. Additionally, we investigate the antiviral mechanisms of TRIM69, a member of the tripartite motif (TRIM) family of proteins. Our results show that TRIM69 restricts HIV-1 independently of microtubule acetylation, indicating alternative pathways and mechanisms at play. By using a doxycycline-inducible TRIM69 expression system in conjunction with CRISPR-Cas9 knockout of αTAT1, we confirm that TRIM69 retains its antiviral function even in the absence of acetylated microtubules. Moreover, TRIM69 demonstrates broad-spectrum antiviral activity, restricting viruses such as chikungunya virus (CHIKV), Coxsackie virus B3 (CVB3), and Zika virus (ZIKV). This comprehensive examination provides significant insights into the adaptability and complexity of HIV-1 in hijacking host cellular machinery, the dispensability of microtubule acetylation in HIV-1 infection, and the multifaceted antiviral mechanisms of TRIM69. These findings not only advance our understanding of HIV-1 biology but also highlight potential targets for novel therapeutic interventions aimed at disrupting the virus\u27s interaction with the host cell. Future research directions include expanding the range of dynein adaptors studied, investigating other post-translational modifications of microtubules, and further elucidating the broad antiviral mechanisms of TRIM69
Tribalism, Science Denial, and its Violation of Stephen J. Gould\u27s NOMA Model
No full textThis presentation explores how tribalism fuels science denial by breaching Stephen J. Gould’s Non-Overlapping Magisteria model, which distinguishes empirical science from value systems. Tribalism leads to group polarization, imposing ideological beliefs on the realm of science and dismissing evidence that threatens group identity. Case studies, like the leaded gasoline controversy of the 20th century, demonstrate how loyalty to identity distorts scientific discourse. Psychological factors, such as confirmation bias, exacerbate this issue. By recognizing these violations, the presentation highlights the importance of interdisciplinary strategies to restore trust in science while respecting Gould’s framework, offering hope in combating science denial
Plastic Mediated Photolysis of Emerging Contaminants in Aqueous Solutions
Full text linkPlastic pollution is ubiquitous. As of 2021, global plastic production was estimated to be 390 million metric tons and of the total plastic waste generated so far, only about 9% has been recycled. Plastic pollution may cause ecological damage in aquatic and terrestrial environments in several ways. Plastic particles can adsorb different compounds and transfer them to animals and then to humans farther up the food chain. Plastic debris in aquatic ecosystems may also transform water pollutants into different, potentially more toxic compounds. My research is concerned with how different types of plastics affect the photolysis of emerging contaminants in freshwater environments. Photolysis studies of triclosan (TCS, 5-chloro-2-(2,4-dichlorophenoxy)phenol and methyl triclosan (2,4,4’-trichloro-2’-methoxydiphenyl ether) have shown that this compound undergoes photolysis twenty to twenty-five times faster when adsorbed on polyethylene (PE) in aqueous solutions than in aqueous solutions alone. TCS is known to undergo photolysis in surface waters to 2,8-DCDD. We are using the light induced unimolecular transformation of TCS to 2,8-dichlorodibenzodioxin (2,8-DCDD) as a probe of the ability of different types of plastics to catalyze the photolysis process. We have found that plastics composed of primarily aliphatic polymers will accelerate the conversion of TCS to 2,8-DCDD while the rate of photolysis of TCS adsorbed onto aromatic polymers (polystyrene and polycarbonate) is much slower. Fluorescence studies of TCS adsorbed onto different plastics suggest that the transfer of adsorbed energy from TCS to the aromatic polymers competes with the fragmentation process, thus slowing the overall rate of photolysis. The surface area of the plastic is also an important factor affecting the rate of photolysis as the rate of photolysis of TCS is found to increase with increasing surface area. Photolysis studies of the flame retardants tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) are consistent with the TCS studies as well
A Kuba Raffia Cut-Pile Textile from the May Weber Ethnographic Study Collection
Full text linkThe May Weber Ethnographic Study Collection at Loyola University Chicago contains thousands of objects, including numerous textiles. This report discusses one specific textile housed in the collection. The object is a raffia cut-pile cloth from the Kuba Kingdom of modern-day Democratic Republic of Congo. This report details the specific description, materials, and creation techniques of the object, as well as attribution of its cultural group, function, and date of creation. The object is further contextualized through the discussion of cultural production and usage of textiles among the Kuba. This includes their ritual and economic uses, as well as their changes over time. Additionally, the textile is discussed in terms of Kuba pattern conventions and the meanings that are associated