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Distribution Of Epidemiological Characteristics Of Low Back Pain Patients Attending To Baghdad Teaching Hospital, Khadija Kamil Salman, Ali Hussein. Al-Hafid, Shatha Ahmed Mohammed Ali Jan 2024

Distribution Of Epidemiological Characteristics Of Low Back Pain Patients Attending To Baghdad Teaching Hospital, Khadija Kamil Salman, Ali Hussein. Al-Hafid, Shatha Ahmed Mohammed Ali

Al-Esraa University College Journal for Medical Sciences

Background: Low back pain (LBP) is a very common health problem worldwide especially in the low and middle-income countries. The LBP may be acute or chronic in nature caused by several medical conditions. The majority of acute low back pain is mechanical in nature due to sprains and strains. Chronic LBP, on the other hand, is most commonly attributed to sciatica, which a radiculopathy condition caused by compression, inflammation and/or injury to the spinal nerve roots. Aims of study: To study epidemiological features of low back pain. Patients and Methods: A cross-sectional study of 440 individuals diagnosed with …

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Working Definitions For Equity, Timothy Berry, Henry Morris, Brian Martensen Jan 2024

Working Definitions For Equity, Timothy Berry, Henry Morris, Brian Martensen

All Resources

The underpinnings of what it means for higher education to support diversity, equity and inclusion is often problematized by different interpretations of key terms necessary to work systematically. Inspired by efforts in both the office of Diversity, Equity and Inclusion and Academic Affairs, we will use the following working definitions in its efforts to increase awareness, understanding and collective action as we work toward our vision and mission.

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David Rezac Honors Portfolio, David Rezac Jan 2024

David Rezac Honors Portfolio, David Rezac

Honors Capstone Portfolios

David Rezac's Honors Portfolio captured in August 2024.

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Carly Kuhlman Honors Portfolio, Carly Kuhlman Jan 2024

Carly Kuhlman Honors Portfolio, Carly Kuhlman

Honors Capstone Portfolios

Carly Kuhlman's Honors Portfolio captured in December 2024.

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Breaking Down Microtubule Formation: Characterizing The Biochemical And Cellular Functions Of The Γ-Tubulin Ring Complex, Adi Y. Berman Jan 2024

Breaking Down Microtubule Formation: Characterizing The Biochemical And Cellular Functions Of The Γ-Tubulin Ring Complex, Adi Y. Berman

Student Theses and Dissertations

The γ-Tubulin ring complex (γ-TuRC) is an essential regulator of the microtubule cytoskeleton. It is composed of>30 individual proteins that include the major component, γ-tubulin, as well as γ-tubulin complex proteins 2-6 (GCP2-6), mitotic-spindle organizing proteins associated with a ring of γ-tubulin proteins 1 and 2 (MOZART, or MZT1 and MZT2), and an actin molecule. This ~2.2MDa assembly regulates microtubule dynamics by facilitating the nucleation of new microtubules, modulating microtubule minus-end dynamics by acting as a minus-end cap, and anchoring microtubules to specify their cellular localization. These three major activities of the γ-TuRC, nucleation, capping, and anchoring, contribute to …

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Vulnerability To G - Quadruplexes In Brca2 - Null Medulloblastoma: A Protective Role For The Pif1 Helicase, Danielle L. Keahi Jan 2024

Vulnerability To G - Quadruplexes In Brca2 - Null Medulloblastoma: A Protective Role For The Pif1 Helicase, Danielle L. Keahi

Student Theses and Dissertations

The reasons why cancer arises in children are not fully understood. Children with biallelic mutations in the essential DNA repair factor BRCA2 are highly predisposed to develop the most common pediatric brain cancer medulloblastoma (MB) before three years of age. Medulloblastoma is often the first malignancy in these children who have a high likelihood of developing several other cancers in their lifetime. MBs have a complex mutational landscape characterized by chromothripsis in p53-deficient tumors and a high level of somatic mutation in many other cases.We utilized a mouse model of spontaneous medulloblastoma development driven by BRCA2 loss in the central …

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On The Second Telomere Maintenance Machine: Structure, Recruitment, And Regulation Of The Cst–Polα/Primase C-Strand Fill-In Complex, Sarah Wang Cai Jan 2024

On The Second Telomere Maintenance Machine: Structure, Recruitment, And Regulation Of The Cst–Polα/Primase C-Strand Fill-In Complex, Sarah Wang Cai

Student Theses and Dissertations

Telomeres are the terminal nucleo protein components of eukaryotic chromosomes that safeguard genome integrity. Human telomeric DNA consists of double-stranded (ds) 5'-TTAGGG-3' repeats terminating in a 3' single-stranded (ss) overhang of the G-rich strand.The sequence and structure of the telomeric DNA is recognized and bound by the six-subunit shelterin complex, which plays critical roles in telomere protection and maintenance. First, shelterin protects the genome by repressing aberrant activation of the DNA damage response at telomeres, which resemble broken DNA ends. Second, due to their location at the end of the chromosome, telomeres present a unique challenge to the canonical DNA …

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Using Small Molecule Tools To Study Atpase Mechanoenzymes, Natalie Jones Jan 2024

Using Small Molecule Tools To Study Atpase Mechanoenzymes, Natalie Jones

Student Theses and Dissertations

The dysregulation of AAA (ATPases associated with diverse cellular activities) mechanoenzymes has been linked to diseases, and chemical inhibitors and activators can be powerful tools to probe mechanisms and test therapeutic hypotheses. However,the structural conservation across the AAA protein family makes designing selective chemical inhibitors challenging. Additionally, unlike chemical inhibitors that can stabilizea single conformational state of an enzyme, activator binding must be permissive to different conformational states needed for enzyme function, and we do not know how AAA proteins can be activated by small molecules. My thesis work covers the development of a chemical genetics approach to inhibit AAA …

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Structual Visualization Of Cytoskeletal Force Tranduction, Ayala Carl Jan 2024

Structual Visualization Of Cytoskeletal Force Tranduction, Ayala Carl

Student Theses and Dissertations

Cells adhere to their surroundings, mechanically interfacing their intracellular actin cytoskeletons with their local extracellular environments. This enables contractile forces generated by myosin motors to mediate transduction of mechanical cues into biochemical signaling pathways by unclear mechanisms. In this thesis, I show that myosin forces elicit conformational transitions in actin filaments (F-actin) that modulate interactions between F-actin and the force-activated cell adhesion protein α-catenin.In vitro reconstitution and cryo-electron microscopy reveal myosin force-evoked superhelical F-actin spirals. Three-dimensional reconstruction and variability analysis uncover extensive asymmetric remodeling of F-actin's helical lattice. This is recognized by α-catenin, which cooperatively binds along individual strands, preferentially …

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A Platform For Analyzing Force Sensitivity And Multivalency In Actin Networks, Joseph Theo Levin Jan 2024

A Platform For Analyzing Force Sensitivity And Multivalency In Actin Networks, Joseph Theo Levin

Student Theses and Dissertations

The physical structure and dynamics of cells are supported by micron-scale actin networks with diverse geometries, protein compositions, and mechanical properties. These networks are composed of actin filaments and numerous actin binding proteins (ABPs), many of which engage multiple filaments simultaneously to crosslink them into specific functional architectures. Mechanical force has been shown to modulate the interactions between several ABPs and individual actin filaments, but it is unclear how this phenomenon contributes to the emergent force-responsive functional dynamics of actin networks. In this thesis, I first present our work engineering filament linker complexes and combining them with photo-micropatterning of myosin …

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Elucidating The Role Of Phospholipid Scramblase 1 In Antiviral Innate Immunity, Gabrielle Paniccia Jan 2024

Elucidating The Role Of Phospholipid Scramblase 1 In Antiviral Innate Immunity, Gabrielle Paniccia

Student Theses and Dissertations

Hosts possess an array of defenses against pathogens, some of which form a baseline protective barrier against infection. This baseline resistance, or intrinsic immunity, is the first layer of cellular defense that a virus must evade or antagonize in order to infect a cell. Intrinsic immunity also forms an important barrier against zoonosis—the transmission of a virus to new species outside its normal host range. Understanding these intrinsic restriction factors and their mechanisms of action can help us understand how pathogens evolve to circumvent or oppose these factors, and identify those pathogens that might be poised to infect new species.In …

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Revealing Smc5/6'S Dynamic Behavior On Diverse Dna Topologies Through Single-Molecule Methods, Jeremy Tzu-Huai Chang Jan 2024

Revealing Smc5/6'S Dynamic Behavior On Diverse Dna Topologies Through Single-Molecule Methods, Jeremy Tzu-Huai Chang

Student Theses and Dissertations

The structural maintenance of chromosomes (SMC) protein complexes serve as critical molecular motors for maintaining genome stability and ensuring faithful genome propagation. As one of the three eukaryotic SMC complexes, the Smc5/6 complex maintains chromosomal stability by coordinating DNA repair processes, promoting successful genome duplication, and silencing viral extrachromosomal DNA. Although these main functionalities have been identified, there is little understanding of how Smc5/6 operates as a versatile molecular machine capable of undertaking different functionalities. And despite being intimately involved with DNA processing reactions, little is known about Smc5/6's dynamic behavior on various DNA substrates, including double-stranded DNA (dsDNA), stretches …

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Pioneer Factors Compete For Epigenetic Factors In Switching Stem Cell Fates, Yihao Yang Jan 2024

Pioneer Factors Compete For Epigenetic Factors In Switching Stem Cell Fates, Yihao Yang

Student Theses and Dissertations

During development, progenitor cells can activate one cell fate while simultaneously silencing another, a process that is tightly regulated in adult tissues. However, this process is often derailed in diseases such as cancers, leading to uncontrolled growth and malignancy. At the crossroads of fate-switching, pioneer factors are a class of transcription factors equipped to bind cognate motifs in closed chromatin. Once they access the closed chromatin, pioneer factors can either act as transcriptional activators or repressors of cell fates by recruiting co-activators or co-repressors. Nevertheless, whether and how a single factor can simultaneously silence the old fate while activating the …

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Developing Easysci, A High-Throughput And Low-Cost Single-Cell Genomic Technique, To Study Aging And Alzheimer's Disease In Human And Mouse Brain, Andras Sziraki Jan 2024

Developing Easysci, A High-Throughput And Low-Cost Single-Cell Genomic Technique, To Study Aging And Alzheimer's Disease In Human And Mouse Brain, Andras Sziraki

Student Theses and Dissertations

Previous single-cell methods are limited by their relatively low throughput and high costs. This prevents most laboratories from performing large-scale cell profiling, complicating the understanding of rare cell type contributions to aging and disease. Moreover, these methods often focus on the 3' end of genes. Without capturing the complete gene body coverage, these technologies have limited detection of specific isoforms. To address these limitations, we extensively optimized a combinatorial indexing-based framework to develop EasySci. We used EasySci to study cell population dynamics associated with aging and Alzheimer's disease in the mammalian brain. This dataset recovered approximately 1.5 million single-cell transcriptomes …

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Cells That Kill: The Chemosensory Cell Types Of Aedes Aegypti Mosquitoes, Olivia Victoria Goldman Jan 2024

Cells That Kill: The Chemosensory Cell Types Of Aedes Aegypti Mosquitoes, Olivia Victoria Goldman

Student Theses and Dissertations

The ability to detect and respond to environmental cues is the fundamental start of any brain function, computation, or behavior. For my doctoral work, I studied chemosensation in the Aedes aegypti mosquito, which can detect cues including human odor, carbon dioxide, and insect repellents. Mosquitoes are human's deadliest predator, causing 700,000 deaths every year through the transmission of malaria parasites and arboviruses including dengue. My research has focused on the molecular underpinnings of mosquito chemosensory cell types. In olfaction, research following the cloning of the first odorant receptors in1991 has shown that each mouse olfactory sensory neuron (OSN) expresses a …

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Discovery And Optimization Of A Family Of Naturally Encoded Antibiotic Compounds That Evade Antibiotic, Adam Rosenzweig Jan 2024

Discovery And Optimization Of A Family Of Naturally Encoded Antibiotic Compounds That Evade Antibiotic, Adam Rosenzweig

Student Theses and Dissertations

Antibacterial resistant infections are an ongoing global health emergency. To combat this,novel potent antibiotics with unique modes of action are required. The classic arsenal of antibiotics used in clinical settings are largely natural products discovered by bulk fermentation of bacterial species isolates that are then extracted and purified to yield a bioactive compound.Unfortunately, this discovery pipeline no longer produces novel molecules, thus new discovery methodologies are essential to continue to identify antibiotic clinical candidate molecules. In the modern era, coupling natural product discovery with sequencing technologies has proven to bean efficient and fruitful method of identifying secondary metabolite natural products …

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Cellular And Circuit Consequences Of A Genetic Locus For Attention, Zachary Gershon Jan 2024

Cellular And Circuit Consequences Of A Genetic Locus For Attention, Zachary Gershon

Student Theses and Dissertations

Animals are constantly bombarded by any number of sensory inputs but have a limited capacity with which to process them. A mechanism for filtering, prioritizing, and directing mental assets is required to prevent sensory overload, enable meaningful comprehension, and allow for further action. Attention is the process of directing cognitive resources toward specific stimuli, which can be dispensed in a top-down manner to carry out higher-order cognitive functions. However, despite extensive and careful study at the molecular, cellular, and, circuit scales, unifying principles have been challenging to elicit. In this thesis, I aimed to provide a new perspective by taking …

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Single-Molecule Studies Of Cftr Gating And Pharmacology, Jesper Bøegh Levring Jan 2024

Single-Molecule Studies Of Cftr Gating And Pharmacology, Jesper Bøegh Levring

Student Theses and Dissertations

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel expressed in the apical membrane of epithelial tissues. Alterations in CFTR that disrupt activity cause cystic fibrosis, a fatal disease which is characterized by systemic salt and fluid dysregulation. By contrast, hyperactivation of CFTR is central to pathogenesis in secretory diarrhea and autosomal dominant polycystic kidney disease. Electrophysiological properties of CFTR have been analyzed for decades. The structure of CFTR, determined in two globally distinct conformations, underscores its evolutionary relationship with other ATP-binding cassette transporters. However, direct correlations between the essential functions of CFTR and extant structures are lacking …

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Proteomic Analysis Of Wnt Signaling And Metabolism Of Fibrolamellar Hepatocellular Carcinoma, James Knox Jan 2024

Proteomic Analysis Of Wnt Signaling And Metabolism Of Fibrolamellar Hepatocellular Carcinoma, James Knox

Student Theses and Dissertations

Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of liver cancer that primarily affects young adults and adolescents.Although characterized as a subvariant of hepatocellular carcinoma (HCC), we have shown it is distinct based on its pathogenesis, patient population and drug response. Our lab has identified a fusion gene DNAJB1::PRKACA that is found in almost all FLC tumor samples sequenced to date. The fusion gene when expressed in mouse liver is sufficient to generate FLC, and elimination of the fusion transcript kills human tumors. The fusion results from a ~400kb deletion on chromosome 19, beginning after the first exon ofDNAJB1, which …

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Anterior Cingulate Function Across Multiple-Time Scales Shapes Learning And Memory, Josue Manuel Regalado Jan 2024

Anterior Cingulate Function Across Multiple-Time Scales Shapes Learning And Memory, Josue Manuel Regalado

Student Theses and Dissertations

We are constantly learning from our everyday experiences about the people we are with, the things we do,where we are, and how we feel. If deemed significant enough,we may choose to remember what we learn for the rest of our lives.For my doctoral work, I studied how a part of the neocortex, the anterior cingulate cortex (ACC),has critical functions across multiple time-scales,from minutes to days-long learning,to weeks-long memory consolidation.The prefrontal cortex, and particularly the ACC portion, is known to be important for goal-directed learning, especially as the relationship between our actions (including effort) and their outcomes (including value) has to …

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Dissecting The Roles Of Cancer Cell Lipid Metabolism In Tumor Progression And Immune Evasion, Mariluz Soula Jan 2024

Dissecting The Roles Of Cancer Cell Lipid Metabolism In Tumor Progression And Immune Evasion, Mariluz Soula

Student Theses and Dissertations

Lipids, along with nucleic acids, carbohydrates, and proteins, are essential biomolecules.These diverse hydrophobic metabolites are composed of fatty acids and include sterols, phospholipids, and glycerides. Lipids can be broken down to fuel energy demands, form the structural basis of all membranes, and can both act as signaling molecules themselves and regulate signaling by impacting membrane fluidity and receptor stability. Given the diverse and essential functions of lipids for normal cell function, it is no surprise that cancer cells leverage lipid metabolic pathways to fuel uncontrolled growth and proliferation and evade cell death. Indeed, enhanced lipid availability has been implicated in …

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Recall Germinal Center And Antibody Responses, Ariën Schiepers Jan 2024

Recall Germinal Center And Antibody Responses, Ariën Schiepers

Student Theses and Dissertations

Repeated exposure to viruses or their antigens elicits anamnestic antibody responses that produce antibodies that are of greater magnitude and affinity compared to those induced after primary exposure to antigen.The anamnestic nature of the response is a result of the recall of memory B cells (MBCs) that have undergone clonal expansion and affinity maturation in germinal centers(GCs) during the primary response. Upon antigen re-encounter ("boosting"), MBCs, aided by enhanced help from memory T cells, efficiently differentiate into antibody-secreting plasma cells. At the same time, boosting induces recall GCs that could in principle either further affinity mature primary-derived MBCs or engage …

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Strain Variation As A Window Into The Neural Logic Of Drosophila Mate Choice, Anna Ryba Jan 2024

Strain Variation As A Window Into The Neural Logic Of Drosophila Mate Choice, Anna Ryba

Student Theses and Dissertations

Drosophila males perform robust, stereo typed courtship routines which have been studied for over a century to understand the genetic and neural underpinnings of flexible, hard-wired behavior. Courtship–particularly on the crowded wild food patches where flies congregate to mate–is a dynamic interaction between a male and surrounding potential partners that requires he integrate multiple sensory cues to direct his efforts efficiently and appropriately. While the behavior follows a similar basic pattern across Drosophila, it can contain elements that are higly species-specific. Here, we described marked variation in one aspect of male courtship preference among inbred lines of the widely studied …

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Transcriptomic Signatures Of Projection Class Neurons For Vocal Control, Stephanie Joy Marcus Jan 2024

Transcriptomic Signatures Of Projection Class Neurons For Vocal Control, Stephanie Joy Marcus

Student Theses and Dissertations

Vocal learning is the ability to modify acoustic structure and syntax of vocalizations. This rare trait is thought to have independently evolved three times in birds and five times in mammals. Vocal learning species exhibit an underlying convergence in brain circuitry, including a direct, forebrain-to-brainstem projection critical for the motor production of learned vocalizations. The remarkable convergence in fore brain vocal circuitry is associated with convergent molecular specializations. In characterizing specializations for vocal motor control across species, we can expand our knowledge of vocal learning and the evolution of this trait. In the first section of this thesis, I generated …

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Neural Mechanisms Of Homeostatic Need And Reward, Bowen Tan Jan 2024

Neural Mechanisms Of Homeostatic Need And Reward, Bowen Tan

Student Theses and Dissertations

Feeding, drinking, sleep, mating, fighting, and parenting are instinct behaviors essential for animal survival. Brain has evolved sophisticated cell types and circuits that encode or fulfill the need states for food, water, sleep, sex, aggression and parenting. These need-sensing neurons monitor both environmental cues and interoceptive conditions to elicit appropriate and specific behavioral programs towards restoration of these needs. The homeostatic control of these need states further enables animals to maintain their survival strength and adapt to the environment. In contrast,dysregulation of these need-sensing neurons causes diseases such as obesity and sleep disorders,both of which are key risk factors for …

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Use Of Genetically Encoded Tools To Interrogate Mechanisms Of Glutathione Homeostasis From Mitochondria To Mice, Rebecca Timson Jan 2024

Use Of Genetically Encoded Tools To Interrogate Mechanisms Of Glutathione Homeostasis From Mitochondria To Mice, Rebecca Timson

Student Theses and Dissertations

Glutathione is an evolutionarily ancient molecule that underlies many critical biological processes across all categories of life. It acts as a cofactor in some metabolic reactions, modifies proteins to modulate their activity, and participates in detoxification of xenobiotic compounds. Despite these wide-ranging functions, glutathione is best known as an antioxidant. Some consider it akin to the fountain of youth because it decreases throughout the course of aging while oxidative damage accumulates.In addition to aging, glutathione dysregulation occurs in a plethora of diseases, including neurodegenerative diseases like Alzheimer's and Parkinson's Disease, liver disease, and metabolic disease, among others. However, the specific …

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Structural Mechanisms Of F-Actin Mechanochemical Regulation And Flexible Network Assembly, Matthew J. Reynolds Jan 2024

Structural Mechanisms Of F-Actin Mechanochemical Regulation And Flexible Network Assembly, Matthew J. Reynolds

Student Theses and Dissertations

The actin cytoskeleton integrates physical and chemical cues from a cell's environment to instruct its behavior, coordinating processes including cell migration, organelle dynamics, and endocytosis. Actin-binding proteins (ABPs) specify actin filament (F-actin) organization to build micron-scale networks which power these cell dynamics. Interactions between ABPs and F-actin are regulated by both biochemical processes and mechanical forces. The mechanisms mediating this interplay remain unclear at the protein structural level. Newly polymerized F-actin hydrolyzes bound ATP to produce metastable ADP-Pi–F-actin, which persists for minutes before phosphate release to yield long-lived ADP–F-actin. I determined cryo-EM structures of both ADP–F-actin and ADP-Pi–F-actin with sufficient …

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Fate, Phases, And Form In Vertebrate Organ Morphogenesis-Uncovering A Role Of Morphogenesis At The Supracellular Scale, Sichen Yang Jan 2024

Fate, Phases, And Form In Vertebrate Organ Morphogenesis-Uncovering A Role Of Morphogenesis At The Supracellular Scale, Sichen Yang

Student Theses and Dissertations

How morphology unfolds from fertilization to birth is one of the most fundamental questions in the life sciences. Self-organization in embryonic development, whereby organs robustly adopt forms through intrinsic processes, is a central feature that remains enigmatic. To achieve greater clarity of such processes, new conceptual and experimental approaches may be needed. Much of work in developmental biology in the past three to four decades has focused on cell and subcellular levels of organization. In line with work of some key conceptual thinkers, we revisit the notions of epigenetics. Rather than confining it to the molecular mechanisms of chromatin remodeling, …

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Towards A Better Understanding Of Facial Movements: Computational Models For Perception, Characterization, And Neural Production, Yanis Tazi Jan 2024

Towards A Better Understanding Of Facial Movements: Computational Models For Perception, Characterization, And Neural Production, Yanis Tazi

Student Theses and Dissertations

Facial movements are the primary medium for non-verbal communication and involve a complex orchestration of muscles controlled by the brain. The ability to interpret and produce these movements enables the expression of a wide range of emotions and social cues, all essential for social interactions. Despite their significance, the neural mechanisms governing facial movements remain poorly understood, hindered by the complexity of muscle coordination and the limitations of traditional, subjective, and labor-intensive analysis methods. To objectively understand facial motor control, this research adopts a three-pronged approach: 1) Developing and interpreting computational models within a novel multi-task training framework to simultaneously …

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The Role Of Gram - Negative Anaerobes In Hidradenitis Suppurativa, Samuel Clay Williams Jan 2024

The Role Of Gram - Negative Anaerobes In Hidradenitis Suppurativa, Samuel Clay Williams

Student Theses and Dissertations

Hidradenitis Suppurativa is a chronic autoinflammatory disease with unknown triggers.New evidence in the last five years has begun to clarify two parts of the pathogenesis of the disease. These two parts are the fundamental role of keratinocyte inflammation from early through late-stage disease and the role of the microbiome as an antigenic and infectious trigger of pathogenesis. Gram-negative anaerobic bacteria (GNA) such as Prevotella, Porphyromonas, and Fusobacterium are commonly identified in HS lesions, and their prevalence in lesions is associated with HS disease severity. Additionally, newly epithelialized structures called "dermal tunnels" are found in severe disease and are associated with …

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