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The Global Water Crisis and Its Impact on Public Health
Get PDFThe author submitted this entry in the Creative Non-Fiction category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.Inspired by national water contamination events, I wrote this piece to explore the broader phenomenon of water-borne illness and its impact on public health
Metabolic Reprogramming in Response to Mitochondrial Electron Transport Chain Dysfunction
Get PDFMitochondrial electron transport chain (ETC) diseases are genetic disorders of energy production with an occurrence rate of approximately 1:4300 and no effective treatment options. Here we show in vitro models of mitochondrial ETC dysfunction display shunting of major carbon sources (glucose and glutamine) from the TCA cycle. Additionally, SLC7A11 (a plasma membrane glutamate/cystine antiporter) promotes pyruvate oxidation in the mitochondria via generation of an electron acceptor, a-ketobutyrate. Furthermore, in the liver, loss of ETC complex I results in no observable clinical or biochemical phenotype, while complex IV deficiency results in steatosis, liver damage, and significant biochemical alterations. The studies herein demonstrate metabolic reprogramming is important in mitochondrial dysfunction; however, the reprogramming is ETC complex and tissue specific
Don't Look at Me
Get PDFThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.Seeing into the mind of an Alzheimer's patient and wondering what those eyes have seen over the years and not having the ability to talk about their lives
What If
Get PDFThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.This work received a Second Place Award in the "Open Verse Poetry" category from all literary works submitted in the 2023 On My Own Time show.Many times, in life we reflect on things in the past, present or future. Sometimes we face situations that we believe outcomes would have been different if we had done something differently. Many times, as we think through life's ups and downs, create new ideas, or try something different, "what if" is phrase that may permeate our thoughts. This poem was a reflection of a time when many situations were in my head with the "what if" pre-text. However, we realize at the end of a long day or deep thought, the "what if" really is just a phrase. Sometimes we let the "what if's" have too much power and hold us back and we have to gently remind ourselves to keep moving
Letters in the Dark
Get PDFThe author submitted this entry in the Fictional Short Story category (Amateur division) for the 2023 On My Own Time (OMOT) Art Show.Written on Memorial Day, this poem is inspired by my contemplation on how I would feel losing a parent in war
Metabolic Outcomes of Aging and Obesity: A Longitudinal Study of the Dallas Heart Study Cohort
Get PDFThe 61st Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 31, 2023, 3-6 p.m., D1.600)Sequestration of body fat into subcutaneous and intra- abdominal (visceral) compartments influences metabolic outcomes. Visceral fat contains more proinflammatory cytokines, and is more metabolically active, with a greater propensity for lipolysis. It is associated with hypertriglyceridemia, increased VLDL synthesis, liver insulin resistance, and reduced HDL cholesterol, and more strongly predicts mortality (Tchernof et al., 2013; Browning et al., 2004; Chalasani et al., 2018; Ibrahim, 2009).
The purpose of this study is to examine adiposity in subjects of the Dallas Heart Study (DHS1 ran 1999-2000, DHS2 began shortly after) and extend the findings in the prospective, longitudinal Dallas Heart and Minds Study (2020- ), allowing the effects of changes in adiposity to be tracked over a nearly 20-year period. We hypothesize that visceral adiposity increases with age and predicts the development of cardiovascular disease and the metabolic syndrome.
Adiposity analysis was undertaken on DHS subjects who completed an abdominal MRI in DHS1 and unique subjects who had completed a whole-body MRI in DHS2. DHMS subjects were former DHS subjects who had an abdominal MRI in DHS and whole-body MRI in DHMS. DHS subjects were scanned using a 1.5T MRI from diaphragm to pelvis with contiguous 10mm slices. Fat contouring was performed on a single slice at L2-L3 using Medis Mass software; DHMS subjects were scanned similarly. Adiposity segmentations in DHMS were performed on the slice corresponding with each subject's DHS segmentation. A prospective method of fat mass prediction from a single MRI slice was used to convert fat volumes to mass (Abate et al., 1997; Neeland et al., 2016). Changes in subcutaneous and visceral fat between DHS and DHMS were calculated to determine the effects on metabolic health.
135 of 254 contoured DHMS subjects had contours in DHS1/2. DHMS subjects had an average weight gain of 1.245kg, BMI increase of 0.792kg/m2, increase in subcutaneous adipose cross-sectional area of 67cm2, and increase in visceral adipose cross-sectional area of 31.102cm2. The change in weight was significantly correlated with changes in subcutaneous (r=0.74, p=0) and visceral adiposity (r=0.59, p=0). Changes in subcutaneous and visceral adiposity were significantly correlated (r=0.23, p=0.006). Finally, DHMS subjects with HOMA IR >2.73 during DHS1/2 had significant percent decreases in weight (p=0.003), subcutaneous adiposity (p<0.001), and visceral adiposity (p<0.001), in contrast to the trends described above.Southwestern Medical Foundatio
The Role of KIBRA in Synaptic Plasticity Across Age
No full textPages 44-164 are misnumbered as pages 32-152.Over the last four decades, neurobiology has gained valuable insight into the cellular and molecular mechanisms of learning and memory. However, a complete understanding of how we learn and remember information remains at the frontier of neuroscience research. In particular, the molecular bases for age-dependent changes in our capacity to learn and remember are poorly understood. Identifying the neural basis of age-dependent changes in learning and memory will not only provide crucial insights into the pathological mechanisms underlying progressive neurological disorders but also guide neurodevelopmentally informed educational strategies and legal policies.
Synaptic plasticity, expressed as persistent increases (long-term potentiation, LTP) or decreases (long-term depression, LTD) in synaptic strength is thought to be a key cellular mechanism underlying cognitive functions such as learning and memory. AMPA-type glutamate receptors mediate the vast majority of fast-excitatory synaptic transmission in the central nervous system, and dynamic AMPA receptor trafficking is critical for many forms of synaptic plasticity. The coordinated movement of AMPA receptors into and out of a synapse is regulated by interactions with multiple proteins including the synaptic scaffold KIBRA (Kidney and Brain Protein). Previous evidence indicates that KIBRA and it's respective binding partners are associated with age-emergent neurological diseases such as Tourette, Schizophrenia, Alzheimer's, and Autism Spectrum Disorders. While there is a growing body of human literature implicating KIBRA in learning and memory, KIBRA's molecular function and contribution to cognitive maturation remains poorly understood. Therefore, this dissertation was designed to focus on the role of KIBRA in synaptic plasticity and AMPA receptor trafficking across the juvenile and adult brain. In Chapter 1, I review the pertinent literature to frame the overall trajectory of this dissertation. Next, in Chapter 2, using novel inducible and conditional KIBRA knock mice, I show that KIBRA acutely influences hippocampal LTP selectively in the adult brain, but not the juvenile brain. These adult-specific deficits in LTP were associated with a reduction in the basal and activity-dependent expression of AMPA receptors and AMPA receptor complex interactors. In Chapter 3, I examine KIBRA's role in LTD. Contrary to published results in conventional KIBRA KO mice on a hybrid C57Bl6N/FVB background, we show that acute manipulation of KIBRA on a C57Bl6N background does not influence hippocampal LTD. Lastly, I show that acute reduction of KIBRA influences GluA2 phosphorylation at S880, which might restrict the recycling of internalized AMPA receptors. Taken together, my data suggest that KIBRA preferentially influences LTP as opposed to LTD. KIBRA's role in LTP is selective to the adult hippocampus and loss of KIBRA reduces the expression and trafficking of AMPA receptors. In Chapter 4, I discuss the implication of this work and layout future directions
Inborn errors of immunity: clinical immunology at UT Southwestern
Get PDFDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin
Transplant as a Medical Trauma: Posttraumatic Stress Symptoms in Pediatric Solid Organ Transplant Patients, a Mixed Methods Approach
No full textPosttraumatic stress symptoms (PTSS) have been reported by pediatric solid organ transplant (SOT) patients well after transplantation. Despite the elevated levels of PTSS in this population, subjective factors associated with PTSS and patients' perception of transplant as traumatic and symptom manifestation of PTSS remains unclear. This study aimed to examine the prevalence of PTSS in pediatric SOT utilizing the DSM-5 PTSD criteria and compare the rate to existing rates in pediatric populations, assess variables associated with PTSS, and explore patients' perception of trauma in SOT and clinical presentation of PTSS.
Forty patients participated in the study with twenty-six completing qualitative interviews. One participant (2.5%) met criteria for PTSD with a slightly larger proportion (n=5;12.5%) being characterized as "partial PTSD likely." Clinical elevated symptoms of hyperarousal were most commonly endorsed. The majority of the sample endorsed functional impairment/distress associated with the PTSS. Patients with lifetime trauma exposure and a post-transplant psychiatric diagnosis reported significantly higher PTSS. Greater perceived life threat, treatment intensity, and maladaptive coping strategies were associated with higher PTSS. Post-transplant medical complications was associated with lower post-transplant PTSS. Lastly, patients described various aspects of SOT as traumatic with symptoms being pervasive across life domains.
Results indicate subclinical levels of PTSS are prevalent in pediatric SOT patients with some experiencing clinically elevated PTSS. Patients with a post-transplant comorbid psychiatric diagnosis are at-risk and would benefit from transdiagnostic assessment and intervention to address symptoms overlapping across disorders. Post-transplant subjective variables and maladaptive coping strategies appear to be an important component to assess, as it relates to PTSS. Objective variables, such as frequent hospitalizations, may be less suggestive of post-transplant PTSS. In-depth examination of the SOT experience and presentation of PTSS via qualitative methods provides insight into how disruption in adolescents' developmental trajectory due to medical trauma is experienced and manifested
Composition, Assembly, and Dynamics of PML Nuclear Bodies
No full textPages 1-130 are misnumbered as page 2-131.Biomolecular condensates concentrate biomolecules into two- or three-dimensional foci that lack surrounding membranes and can scale in diameter from tens of nanometers to several microns in cells. Promyelocytic leukemia nuclear bodies (PML NBs) are a biomolecular condensate conserved across mammalian, avian and reptilian species. They are primarily composed of the PML protein, and over two hundred additional proteins have reported associations with PML NBs. While the precise function of PML NBs has remained ambiguous, they have been implicated in diverse cellular pathways, from viral response to epigenetics. Previous studies surrounding PML NBs in cells have been largely qualitative, and the physical mechanisms underlying PML NB assembly, dynamics and composition remain largely unknown. In this thesis, I have used quantitative imaging methods in live cells to elucidate properties of PML NBs in their physiological environment. I identified the role of a PML post translational modification, addition of the small ubiquitin-like modifier (SUMO) at lysine 65, in balancing the composition with the dynamics of PML NBs. Additionally, I discuss PML NB behaviors throughout the cell cycle, investigate client recruitment into PML NBs, and evaluate the contribution of ordered domains in PML in PML NB formation. Finally, I analyzed different models for PML NB assembly and propose future lines of study that could uncover their assembly mechanism. Collectively, my work sheds light on a natural condensate and illustrates the complexity of condensate regulation in vivo