15849 research outputs found
Sort by
Computational Analysis and Characterization of the Inducible 1-Cysteine Peroxiredoxin Promoter in the Malaria Parasite Plasmodium
No full textMalaria afflicts over 200 million people annually, which results in over half a million deaths, primarily in sub-Saharan Africa. Malaria parasites are complex protozoan organisms that inhabit two hosts: humans, the site of asexual reproduction, and the Anopheles mosquito, where sexual reproduction occurs. To withstand the hostile extracellular environment of the Anopheles mosquito, the malaria parasite Plasmodium berghei employs antioxidant defense mechanisms. Previous work suggests upregulation of 1-Cysteine Peroxiredoxin (1-CPxn) when the mosquito uptakes a blood meal containing the parasite. The parasite must acclimate to the harsh environmental conditions of the mosquito midgut: find a way to counteract reactive oxygen species (ROS) released by the mosquito’s immune system or die. We hypothesize that the parasite senses a threat to its survival and responds by activating an antioxidant response motif (ARM), resulting in the expression of 1-CPxn. In the present work, I aim to locate ARM(s) within the 1-CPxn promoter through a “promoter bashing approach,” using a combination of computational and experimental tools. Informed by computational prediction of ARM sites, I produced luciferase reporter constructs with the goal of transforming those into malaria parasites
“The Wonderful Swiftness of the Soul”: Mental Movement and Religious Ethics in Medieval English Literature
No full textThis dissertation analyzes conceptual metaphors of psychological motion and stability in medieval English religious literature. I trace how language itself structures cultural approaches to epistemology, spiritual knowing, and virtue. Chapter One examines Alfred’s translation of Neoplatonic metaphors of psychological movement in the OE translations of The Consolation of Philosophy and Augustine’s Soliloquies. I argue that the reconfiguration of these metaphors into images of stability reveals an epistemology centered on certainty. Chapter Two compares the omission of motive psychological metaphor in Cynewulf’s Juliana and Ælfric’s “St. Agatha and St. Lucy” in process of translation. While Cynewulf’s depiction of virtue through stability allies him with common Old English idiom, Ælfric’s commitment to Platonism motivates him to avoid of metaphorical stability and movement alike. I then examine Ancrene Wisse and the “Katherine Group” and their rhetorical use of metaphor from a range of cultural and linguistic source domains. These metaphors invoke associations from their original contexts to fuse the secular with the sacred. Finally, I suggest that Julian of Norwich develops Boethian metaphors of both movement and stability in service of her incarnational theory of the soul in Revelations of Divine Love. My research traces the ever-changing nature of the English language and psychology through the cross-cultural discourses instantiated by war, invasion, trade, and the translation of Greek and Arabic tracts into Latin. I argue that linguistic flux, whether driven through multilingualism, time, or innovations of literary discourse and register, is a structuring force for cultural ethics regarding the body, mind, and soul. Religious and pedagogical approaches to their governance are therefore deeply embedded in the conceptual framework of language as well as literary genre and linguistic registe
Fear of Victimization, Trust, Security, and Public Spaces in Guatemala
No full textThis dissertation explores fear of victimization, personal encounters with crime, perceptions of institutional trust, support for informal justice practices, and avoidance of spaces in Guatemala. Institutional trust—understood as individuals’ confidence in the police, judiciary, and correctional systems, particularly their fairness and effectiveness—is vital for democratic governance and social stability. High levels of trust in legal institutions can foster civic engagement, reduce social fragmentation, and encourage public cooperation in crime prevention. In contrast, diminished trust may lead individuals to withdraw from formal systems of justice, limiting the state\u27s capacity to function effectively. Utilizing nationally representative data from the National Survey of Perceptions of Public Safety and Victimization, this research addresses three key questions: 1. How do prior experiences of violent and non-violent victimization, as well as fear of victimization, shape levels of trust in the police, courts, and prisons—are there differences by sex and ethnicity? 2. What individual-level factors predict support for informal justice mechanisms in Guatemala, and are there differences by sex? 3. Does fear of victimization influence attendance at leisure spaces such as movie theatres and sports venues, and are there differences by sex and ethnicity? A growing body of research shows that victimization and fear of crime significantly affect perceptions of the criminal justice system. The first study explores trust in police, courts, and correctional institutions, analyzing how different forms of victimization—violent, non-violent, and multiple incidents—relate to trust. It also examines differences by sex and ethnicity. Findings reveal a negative association between fear and institutional trust. Notably, prior non- violent victimization is linked to lower levels of trust, underscoring the complex relationship between experience and perception. Significant group differences also emerge: Ladino respondents with moderate to high levels of fear report lower trust in the justice system, while women who have experienced victimization exhibit comparatively higher trust. The second study focuses on informal justice—defined as the resolution of disputes and enforcement of norms outside formal legal institutions. I analyze individual-level support for informal justice through three crime scenarios, with particular attention to differences by sex. I examine how fear of victimization, prior violent and non-violent victimization, and institutional trust shape support for informal mechanisms. Results show that individuals who report fear, report prior non-violent victimization, or express higher institutional trust are less likely to support informal justice practices. These findings raise concerns about the legitimacy of formal institutions, as widespread reliance on informal justice may encourage parallel systems and normalize vigilante behavior. The third study addresses how fear of victimization affects access to leisure spaces, an important but often overlooked dimension of quality of life. Prior research suggests that fear significantly limits people’s use of public spaces, especially when physical disorder—such as broken streetlights or vandalism—is present. This analysis identifies vulnerable populations in Guatemala by examining whether fear, gender, and ethnicity influence avoidance of leisure spaces. Findings indicate that women and Indigenous individuals are more likely to avoid movie theatres and sporting events due to elevated fear or prior victimization. These results highlight the need for public safety interventions that expand access to safe, inclusive, and community- oriented leisure spaces
Muscarinic Acetylcholine Receptor 1: Implications for Precision Medicine and Rett Syndrome Therapeutics
No full textRett syndrome (RTT) is a rare neurodevelopmental disorder caused by mutations in the gene coding for methyl-CpG binding protein 2 (MeCP2). Currently, there is no cure for RTT and few effective treatment options to address the social, cognitive, motor, and respiratory symptoms that patients face. With the goal of identifying novel targets, our lab performed RNA-sequencing experiments in human autopsy samples and found decreased levels of the M1 muscarinic acetylcholine receptor. We have established that potentiation of this receptor in a Mecp2+/- mouse model of RTT rescues social, cognitive, and respiratory phenotypes, providing support for using drugs that act on M1 for RTT. The efficacy of this compound was linked to the Gsk3β and NMDA receptor signaling axis, which others have targeted and found to be therapeutic in RTT. While these results were exciting, different mutations in MeCP2 confer distinct transcriptional disruptions and we next addressed the possibility that not all RTT patient subpopulations would have decreased M1. When M1 expression was binned by MeCP2 mutation, it was found that patients with the common R168X and R270X mutations had decreased expression, while those with R255X, R306C, and T158M mutations did not. This raises the question of whether target disruption is needed for the efficacy of drugs that act on the M1 receptor. This potential challenge was addressed by efficacy testing of the M1 positive allosteric modulator (PAM) VU595 in Mecp2+/R168X, Mepc2+/T158M, and Mecp2+/R306C mouse models. Our results established a relationship between low M1 expression and compound efficacy of VU595 in RTT. While VU595 has demonstrated efficacy, the population of neurons driving its therapeutic effects is unclear. Using whole-brain light sheet imaging, we found that c-Fos expression is increased throughout the brain in Mecp2+/- mice but is normalized after VU595 administration. Data from this experiment suggests that excitatory projections from fore-and midbrain regions project to and activate inhibitory neurons in the brainstem to exert a cooling effect on neuronal activity. These experiments further advocate for the development of muscarinic PAMs for RTT by identifying the brain regions and patient populations where they are most likely to be effective
Thienopyrimidine-Based Estrogen Receptor Degraders Adopt Unique Ligand Binding Poses to Elicit Anti-Proliferative Activities in Estrogen Receptor Positive Breast Cancer Cells
No full textOne in eight women will be diagnosed with breast cancer in their lifetimes. Estrogen receptor alpha (ER) drives breast cancer pathology and is expressed in approximately seventy percent of tumors. Hormone therapies are used to treat and prevent the metastasis of ER+ breast cancers and these patients have favorable 5-year survivals. However, most breast cancer patient deaths remain in ER+ patients. While the next generation of antiestrogens have shown promise in the advanced setting, more work needs to be done to fully address these mortalities. ER is a ligand-dependent master transcriptional regulator, whereby ligand-specific ER conformational ensembles redirect multiple programs to produce oncogenic or therapeutic endpoints. To better understand ER structure-activity relationships, we have developed new antiestrogenic small molecules based on a thienopyrimidine scaffold. Comprehensive structural, ER activity, and cancer endpoint profiling shows that these new molecules adopt a unique ligand binding pose, which perturbs new structural elements within the orthosteric hormone binding pocket. These molecules downregulate ER target genes and halt the proliferation of ER+ breast cancer cells
Cultivating Community-University Partnerships within the Chicago Region Food System
Get PDFWe interviewed 22 organizations in the Chicago Regional Food System to gain insights on their current initiatives, assets, challenges, future visions, and perceived roles of universities in advancing their work. We analyzed themes to report on strong consensus or varied perspectives related to this work. This report aims to advise Loyola’s School of Environmental Sustainability\u27s future work and collaboration activities with Chicago Food System organizations
Investigating the role of out-of-school experiences in racial and ethnic identity formation for Black youth within an ecological model
Get PDFRacial and ethnic identity formation is associated with psychological well-being and this is especially true for youth of color, including Black adolescents. Currently, there is a dearth of literature examining influences on this facet of identity during adolescents, outside of parental socialization and school-related factors. Participation in organized out-of-school activities has been associated with positive outcomes, such as social and emotional well-being, which, in turn, is related to identity formation. The goal of the present study was to better understand the relation between out-of-school experiences and racial and ethnic identity among Black adolescents. Participants included Black identifying adolescents, ages 14-19 (n=181; M age= 16.30 (SD= 1.38; 69% female). More participation in out-of-school experiences (i.e., total, types, and intensity) was significantly associated with higher reported racial and ethnic identity formation. Latent classes analysis of out-of-school experiences revealed that classes characterized by a higher breadth of experiences reported high racial and ethnic identity while the class characterized by low participation in out-of-school experiences reported significantly lower ratings of racial and ethnic identity. These findings suggest that out-of-school experiences are associated with racial and ethnic identity formation among Black youth, but future work is needed to examine the mechanisms that support this dynamic exchange. As racial and ethnic identity formation is associated with well-being, these findings have strengths-based clinical, programmatic, and community implications
The Experience of Transition to Self-Management for Saudi Adolescents with Type I Diabetes
Get PDFIn Saudi Arabia (SA), between 2011 and 2021, there has been a 108% increase in death rates due to diabetes. Every year, around 3,800 Saudi children and adolescents under the age of 19 are diagnosed with Type I Diabetes (TIDM). Saudi adolescents with TIDM have less glycemic control than adults and younger children. If left untreated, inadequate glycemic control may hasten the onset of diabetes complications and early death. As adolescents with TIDM grow older, they are expected to take on more independence in Self-Management (SM) of their diabetes. The poor clinical outcomes of adolescents with diabetes, the onset of life transitions, and the transition experience to SM in this age group intensify the need to better understand the process of adolescent transition to SM. There are no research studies on the experience of Saudi adolescents with TIDM transition to SM. The purpose of this study was to explore and describe the experience of Saudi adolescents with TIDM as they transition to SM. Informed by Meleis’s theory of transition, the study used a qualitative descriptive design and individual interviews with middle and late-age Saudi adolescents in SA. The local experience was presented in this dissertation as voiced by 10 Saudi adolescents which is currently lacking in the Saudi diabetes literature. It was found that although adolescents go through specific and progressive steps as they transition to SM, their individual contextual factors along with their unique life transitions determine the shape of their transition experience. Failing to account for these contextual factors and life transitions would prevent a comprehensive understanding of the transition experience to SM. This study provided detailed descriptions that would potentially lead similar studies not only about adolescents with TIDM, but also adolescents with other chronic conditions
