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Weighing the Heart: A Case of Tuberculous Pericarditis
Get PDFhttps://digitalcommons.library.uab.edu/uabh-rd-all/1424/thumbnail.jp
Comparative Analysis of Lewy Body Dementia and Other Dementia Types
Get PDFhttps://digitalcommons.library.uab.edu/uabh-rd-all/1438/thumbnail.jp
Context-Dependent Functional Connectivity During Attention Orienting And Reorienting: Comparing Individuals With Schizophrenia And Controls
Get PDFAttentional deficits are a well-established feature of schizophrenia, impacting various functional domains. Previous research suggested altered connectivity within attention networks may underlie these deficits, but few studies have examined how these net-works dynamically interact during different types of attention processes. In this study, we investigated functional connectivity patterns during attentional orienting and reori-enting to social and nonsocial cues in 25 individuals with schizophrenia and 25 controls. Participants completed a modified Posner spatial cueing task with both social (eyes) and nonsocial (arrows) cues during fMRI scanning. Using generalized psychophysiological interaction analysis with the left lateral occipital cortex (LOC) as a seed region—selected based on its consistent activation across conditions—we examined task-specific changes in functional connectivity. Behaviorally, individuals with schizophre-nia showed overall slower reaction times but demonstrated higher accuracy specifically during social trials compared to controls. During nonsocial orienting, controls showed stronger connectivity between the LOC and insular cortex/precentral gyrus, along with weaker connectivity with precuneus cortex and paracingulate gyrus, while individuals with schizophrenia showed no significant connectivity patterns. During social reorient-ing, controls demonstrated stronger connectivity between the LOC and regions includ-ing the middle temporal gyrus, postcentral gyrus, and insular cortex, while individuals with schizophrenia showed no significant connectivity changes. Additionally, during nonsocial reorienting, individuals with schizophrenia showed weaker connectivity be-tween the LOC and fusiform gyrus. These findings suggest disrupted functional integra-tion of attention networks in schizophrenia across both orienting and reorienting pro-cesses, with particularly pronounced alterations in network connectivity during social attention conditions
Stimulation And Quantification Of Dopamine-Associated Behaviors
Get PDFDopamine (DA) is a neurotransmitter involved in the regulation of essential behaviors, including motor control and reward processing. Alterations in DA levels can significantly modulate these behaviors: increased DA release is associated with heightened locomotion and enhanced preference for rewarding stimuli. Therefore, measuring behavioral changes in vivo provides critical insight into DA release and function. In this study, we quantified DA-associated behaviors by radiolytic stimulation of the Drosophila A-isoform of the transient receptor potential ankyrin type-1 A (dTRPA1(A)) channel and investigated how the human-immunodeficiency virus (HIV) and its secreted protein, the trans-activator of transcription regulatory protein (Tat), alter drug-induced behaviors. In Drosophila, dTRPA1(A) is an evolutionary conserved detector of noxious chemicals, and it is highly sensitive to reactive oxygen species (ROS) and hydrogen peroxide (H2O2). In biological systems, UV light and X-rays rapidly generate ROS and H2O2, triggering dTRPA1(A) activation. Radiolytic stimulation of the heat insensitive dTRPA1(A)10b isoform may provide a new method of non-invasive, deep-tissue control of genetically defined cells in mammalian models. Since our findings demonstrated that X-rays stimulated DA release, we further investigated X-ray-induced changes in DA-associated behaviors. HIV and amphetamine (AMPH) use disorder (AUD) is a complex bidirectional relationship, where AMPH use facilitates HIV transmission, and HIV infection has been linked to increased AMPH use. Although the underlying mechanisms supporting this disorder are unknown, Tat, a protein secreted by HIV infected cells, has been implicated in enhancing escalation of AMPH use. Tat has been shown to interact with the anionic lipid phosphatidylinositol 4,5-bisphosphate (PIP2), the key regulator in DA uptake and release by the human dopamine transporter (hDAT). Tat’s interaction with PIP2 may ultimately impair hDAT-mediated, AMPH-induced DA release and potentially drive increases in AMPH intake (escalation) to compensate for the reduction in rewarding stimuli. Thus, we sought to investigate Tat’s role in the regulation of AMPH-associated behaviors. To quantify DA-associated behaviors, we utilized DeepLabCut, a neural-network-based pose estimation program, and custom analysis code. We also developed a novel behavior assay incorporating a 3D-printed chamber to measure AMPH escalation and preference. This approach provides a quick and accurate framework for analyzing complex behaviors
Mesenchymal Hippo Signaling in Lung Development and Disease
Get PDFDuring both lung development and regeneration, the proper coordination of different cellular populations working in concert are vital to proper development and wound repairs. Myofibroblasts, highly contractile mesenchymal cells, are vital the organization of cells during lung development and to the remodeling of the extra cellular matrix (ECM) during regeneration. As important as myofibroblasts are, their apoptosis or differentiation to a less contractile phenotype is equally important to normal development and regenerative processes. Excessive differentiation of myofibroblasts or the improper localization of myofibroblasts are associated with pulmonary fibrosis, which is characteristic of lung disease, such as bronchopulmonary dysplasia or idiopathic pulmonary fibrosis. Fibrosis permanently alters lung function and persistent fibrosis can ultimately result in death. The Hippo signaling pathway is believed to play a key role in the appropriate temporal-spatial expression of various mesenchymal cell populations, including myofibroblasts. The Hippo signaling pathway is better characterized in lung epithelial cells, while studies specifically within the mesenchyme are not as robust. In this study, we examine the interplay between mesenchymal and epithelial lung cells. We particularly focus on the Hippo pathway in the mesenchyme, while also considering how the mesenchymal Hippo signaling influences the differentiation and properties of mesenchymal cells as well as how it influences epithelial Hippo signaling. We examined how mesenchymal and epithelial cell signaling differ in part due to cell specific availability of transcriptional co-factors, such as Snail and Slug, which are found within mesenchymal cells and are lacking within epithelial
Endothelial Cell Cd36 In Alzheimer’S Disease And Breast Cancer Progression
Get PDFVascular endothelial cells (ECs) are increasingly recognized as a distinct class of innate immune cells, with CD36, an innate immunity receptor, playing a pivotal role in regulating immune function and its regulation, angiogenesis, cancer progression, brain related disorder as well as the exchange of nutrients and waste. To investigate this further, we developed EC-specific CD36 knockout mice using the translating ribosome affinity purification (TRAP) technique. By isolating ribosome-bound mRNA directly from vascular endothelial cells in vivo in these knockout and control mice, we conducted deep RNA sequencing and transcriptional profiling. Our findings revealed that CD36 deficiency in brain endothelia led to the downregulation of gene signatures associated with innate immune memory, alongside changes in the expression of genes related to innate immunity and immune responses, which were linked to fatty acid (FA) metabolism. Additionally, single-nuclear RNA-seq analysis of brain tissues from Alzheimer’s disease (AD) patients highlighted the critical involvement of a subset of CD36-positive brain ECs in disease progression. . Endothelial cells in blood vessels and lymph nodes play a crucial role in regulating the spread of breast cancer. They contribute to tumor growth and metastasis by secreting various factors that activate breast cancer cells, including cytokines and breast cancer stem cell-related signals. To further elucidate the significance of endothelial cells in breast cancer progression, we examined the viability, migration, proliferation, and apoptotic potential of ER+ breast cancer cells. Our findings demonstrate that the combination of Fc3TSR and Everolimus effectively inhibits the growth of ER-positive breast cancer cells
Investigating Potential Therapeutic Vulnerabilities And Elucidating Molecular Mechanisms For The Tumor Suppressors Nfkbia And Anxa7 In Diffuse Gliomas
Get PDFGliomas, and especially diffuse gliomas, can be a devastating disease when attempting treatment in the clinic. Diffuse gliomas are typically malignant and pose definitive problems with respect to patient care predominantly due to their ability to exist outside of the bulk tumor by invading into the surrounding brain parenchyma. Consequently, not every cancerous cell can be fully removed by surgical resection and therapeutic resistance, so the stem-like population left behind can repopulate a recurrent tumor from a single cell. There is a desperate need for pinpointing novel therapeutic vulnerabilities in diffuse gliomas, which could potentially involve the targeting of key genes essential for their survival. One avenue for augmenting the treatment efficacy for diffuse gliomas includes restoring or reintroducing tumor suppressors that are lost during gliomagenesis. Iκβa, encoded by the NFKBIA gene, is a well-known tumor suppressor that canonically sequesters NF-κB in the cytoplasm, preventing it from entering the nucleus to enact its transcription factor (TF) activity. However, we identified an arguably more prevalent mechanism for Iκβa entirely independent of NF-κB signaling that was further characterized via separation of function (SOF) mutants. We found demonstrated Iκβa capable of direct TF activity that could be the more catastrophic function of Iκβa being pruned during gliomagenesis to allow for diffuse glioma tumor growth. Another intriguing tumor suppressor gene for gliomas is ANXA7, which encodes for both isoforms of the Annexin A7 protein. As one of the members of the Annexin A family in humans, Annexin A7 has been understudied within the context of gliomas. This lapse in the literature should be filled when considering the alternative splicing of Annexin A7 can yield either full-length isoform 1 (I1) or isoform 2 (I2) that is generated through the skipping of cassette exon 6. We found I1 alone to facilitate the degradation of epidermal growth factor receptor (EGFR) following activation in clinically relevant glioma models. Determining which tumor suppressor genes are integral to gliomagenesis possesses unequivocal therapeutic potential for diffuse glioma patients, especially those of higher grade. We determined the significance of two distinct but uniquely prevalent tumor suppressors that are essential for glioma stem cell maintenance. Although there are more prevalent genes aside from just NFKBIA and ANXA7, our findings warrant the investigation into their clinical relevance. Developing therapies to target these tumor suppressors can potentially provide patients with better long-term survival. Furthermore, these tumor suppressors play a significant role in both low- and high-grade diffuse gliomas, including the most aggressive form known as glioblastoma. Successful rescuing of either of these tumor suppressors by any of the proposed therapeutic strategies could provide benefits for patients by significantly prolonging their overall survival
Understanding Submerged Plant Microbiome And Exploring Plant Microbe Interaction Through Plasma Optimization Studies
Get PDFThe master\u27s thesis presents research on enhancing plant resilience and growth through the study of the microbiome of submerged aquatic plants and the application of plasma technology in agriculture. We isolated 177 endophytic microbial strains from submerged plants collected from various locations. Screening revealed 50 strains producing ACC deaminase, an enzyme that mitigates plant stress by reducing ethylene levels. Predominant genera included Pseudomonas, Bacillus, and Acinetobacter. Metagenomic analysis characterized the diverse bacterial communities associated with these plants. Different plasma treatments were tested to optimize their effects on plant growth. Atmospheric jet and globe plasma treatments significantly improved root length and chlorophyll content. These treatments also maintained or enhanced the growth of beneficial microbes, including those with ACC deaminase activity. This study contributes to understanding plant-microbe interactions and demonstrates the potential of plasma technology for sustainable, climate-resilient agriculture. Findings suggest that ACC deaminase-producing microbes and optimized plasma treatments can promote plant health and resilience. Chapter 1 focused on understanding the microbiome of submerged plants like Hydrilla and Pondweed. We aimed to identify microbes producing ACC deaminase to mitigate plant stress by degrading ACC, a precursor to ethylene, and explored microbial diversity through metagenomic analysis. Sample collection from various sites yielded 177 endophytic microbial strains from 162 samples across 15 locations. Techniques included microbial isolation, DNA extraction, amplicon sequencing, and screening for ACC deaminase activity using Dworkin and Foster minimal medium with ACC as the sole nitrogen source. Results showed 50 strains with ACC deaminase activity, indicating potential as bioinoculants for sustainable agriculture, particularly for aquatic crops like rice and watercress. Key genera included Pseudomonas, Bacillus, and Acinetobacter, with metagenomic analysis revealing diverse communities dominated by Proteobacteria and Actinobacteria. Future directions included functional metagenomics to confirm gene expression, screening for indole-3-acetic acid production, and phenotypic screening of treated plants. Chapter 2 optimized plasma treatment for enhancing plant growth and exploring its effects on plant-microbe interactions, with applications in climate-smart agriculture. Different plasma types like glow discharge, atmospheric jet, and globe plasma were tested under varying conditions from 10 seconds to 5 minutes. Measurements included chlorophyll estimation, root length calculation, and microbial quantification assays focusing on ACC deaminase-positive strains like Pseudomonas fluorescens. Results showed significant effects on chlorophyll content and root length, particularly at 1-minute exposures with atmospheric jet and globe plasma, maintaining or enhancing beneficial microbial growth without promoting pathogens. Future directions included further exploration under stress conditions, understanding molecular mechanisms, and investigating plasma-induced nodule formation in non-leguminous plants
Combining Checkpoint Therapy and IL-6 Receptor Inhibition in Non-Small Cell Lung Cancer
Get PDF2025 Spring Expo Poster Presentation Biological & Life Scienceshttps://digitalcommons.library.uab.edu/sp-expo/1047/thumbnail.jp
Impact of Professional Organizations on Nursing Student Success
Get PDF2025 Spring Expo Poster Presentation Health Sciences & Health Professionshttps://digitalcommons.library.uab.edu/sp-expo/1048/thumbnail.jp