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City Whisper
Full text linkThe author submitted this entry in the 10-Word Story category (Amateur division) for the 2025 On My Own Time™ (OMOT) Art Show.This story is inspired by the transient, anonymous intimacies of urban life. It captures the atmosphere of a city at night--the cool glow of neon, the reflections on wet surfaces--creating a backdrop for fleeting human connections and the subtle exchange of hidden thoughts. It's about the moments of quiet drama and unspoken narratives that unfold constantly amidst the bustling indifference of a metropolitan environment
Kidney stone disease in 2025: something old, something new, something borrowed, something bluetooth
Full text linkDetailed 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
Worth
Full text linkThe author submitted this entry in the 10-Word Story category (Amateur division) for the 2025 On My Own Time™ (OMOT) Art Show.Men's mental health and self-worth are often times overlooked. Men are as deserving to allow themselves to receive the love that they give. It is acceptable to move on. Self-love can be that simple--displayed in 10 words
Understanding the Language of Measles: A Historical and Medical Perspective
Full text linkThe author submitted this entry in the Creative Non-Fiction category (Amateur division) for the 2025 On My Own Time™ (OMOT) Art Show.Recent outbreaks of Measles inspired me to explore the etymology of the disease and its symptoms
He Heard You
Full text linkThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2025 On My Own Time™ (OMOT) Art Show.Written in challenging times, when God's word speaks to us and provides comfort
Beautiful Torture
Full text linkThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2025 On My Own Time™ (OMOT) Art Show.Personal growt
Circadian Timekeeping of Body Temperature by the Mammalian Suprachiasmatic Nucleus
Full text linkThe circadian rhythm of body temperature (CRT) is a universal cue for entraining the peripheral clocks in mammals. The hypothalamic suprachiasmatic nucleus (SCN) is required for generating the ~24-hour rhythms of body temperature (Tb); however, the neural mechanism underlying this regulation remains poorly understood. Here, we searched for circadian clocks in the SCN that are necessary for maintaining CRT in mice using a stepwise loss-of-function genetic approach and radiotelemetry recordings. We show that genetic deletion of Bmal1, a non-redundant clock gene for driving the cell-autonomous circadian clock, broadly in the forebrain inclusive of the SCN sufficiently abolished the circadian rhythmicity of Tb. In contrast, genetic deletion of Bmal1 specifically from the neuromedin s (Nms)-expressing neurons in the SCN progressively impaired CRT over the course of a month in constant darkness. Interestingly, synaptic inhibition of a subpopulation of these Nms neurons co-expressing arginine vasopressin lengthened the circadian period of CRT. Finally, local chemogenetic inhibition of the SCN Nms neurons prevented hypothermia specifically during the late subjective night and sustained until subjective dawn, but not at other circadian times of a day. Together, our findings unveiled a role of the SCN Nms neurons in the circadian modulation of Tb with a hypothermic role manifested at late night, possibly to prepare the nocturnal mice for rest in the day
Glucose-6-Phosphatase in Metabolic Disease and Cancer
No full textInborn errors of metabolism (IEMs), which are caused by germline mutations in metabolic enzymes and nutrient transporters, provide an opportunity to observe how discrete metabolic defects cause human disease. Glycogen Storage Disease Type 1a (GSD1a), or von Gierke's disease, is an autosomal recessive IEM caused by defects in Glucose-6-Phosphatase, Catalytic Subunit (G6PC), the terminal enzyme in both glycogenolysis and gluconeogenesis. Fasting hypoglycemia, a prominent symptom of GSD1a, is understandable because of G6PC's role in hepatic glucose output. Other metabolic anomalies in GSD1a, including debilitating lactic acidosis and hyperuricemia, are assumed to be consequences of glucose-6-phosphate accumulation, although the mechanism has not been explored in detail. Late sequela of GSD1a includes the formation of liver adenomas and carcinomas without obvious signs of liver injury or cirrhosis. Here we show that the oncogenic transcription factor c-Myc potentiates metabolic rewiring and drives lactic acidosis and hyperuricemia in a mouse model of GSD1a. Using metabolic profiling and isotope labeling strategies in both in vivo and cultured cell models of GSD1a, we found enhanced use of both glycolysis and the pentose phosphate pathway, which produce precursors to lactate and urate, respectively.
Transcriptomic analysis revealed that these metabolic changes were accompanied by increased transcription of genes in both pathways. In addition to stimulating these metabolic pathways, we observed that G6PC deletion stimulates hepatocyte proliferation in culture and in the liver. Overall, the transcriptomic profile of G6PC-deficient livers indicated enhanced expression of c-Myc-responsive genes, and c-Myc itself was markedly induced within two weeks of G6PC deletion. c-Myc regulates many aspects of glucose metabolism in cancer, and 75% of GSD1a patients eventually develop hepatic adenomas (HCAs) and hepatocellular carcinomas (HCCs). However, c-Myc activation occurred long before the appearance of malignancy in these mice. We tested if c-Myc potentiates the metabolic anomalies initiated by G6PC deletion. We found modest genetic silencing of c-Myc normalized genes and metabolites related to glycolysis and the pentose phosphate pathway.
In both the liver and a hepatocyte cell line, suppressing c-Myc attenuated the accumulation of lactate and urate, despite persistent G6PC deficiency and glycogen accumulation. We found that G6PC deficiency induces a hyperproliferative state in a hepatocyte cell line and premalignant livers, and c-Myc silencing reduced these effects. Finally, we characterized tumors that form in GSD1a as having a strong c-Myc gene signature as well as a low mutational burden relative to sporadic liver cancers, without signs of liver injury or cirrhosis. Overall, our results demonstrate that a monogenic metabolic defect in a human IEM induces a localized oncogenic response in the liver that drives systemic metabolic dysfunction and may contribute to carcinogenesis
Characterization of Mitochondrially Targeted T3SS2 Effectors in Vibrio parahaemolyticus
No full textVibrio parahaemolyticus (V. parahaemolyticus) is a Gram-negative bacterial pathogen that is the leading cause of bacterial seafood-borne acute gastroenteritis. All strains of V. parahaemolyticus harbor the type III secretion system 1 (T3SS1), which is dispensable for virulence in humans. Pathogenic strains harbor an additional type III secretion system (T3SS2) that mediates host cell invasion to form a protective replicative niche and is responsible for the enterotoxic effects. To date, only nine T3SS2 effectors have been identified within the T3SS2 pathogenicity island that contains 30-50 additional uncharacterized proteins.
In the first part of this study, we performed a proteomics screen to identify T3SS2 effectors and found VPA1328, a novel T3SS2 effector recently identified as a member of the VopG family of predicted kinases. Coupling structural modeling and remote homology prediction with biochemistry, we determined that residue D205 in VPA1328 was critical for its catalytic activity. Using cell biology, we found VPA1328 localizes to the mitochondrial matrix of eukaryotic cells. Interestingly, while expression of VPA1328 did not affect cell death or mitochondrial membrane potential in HeLa cells, it decreased mitochondrial oxygen consumption rates and inhibited yeast growth. This growth phenotype was exacerbated by forcing the cells to use mitochondrial respiration for energy production. Metabolic analysis of the yeast expressing VPA1328 showed increases in fumarate, dihydroorotate, N-acetylputrescine, N,N-dimethylarginine, and glycerophosphocholine, suggesting changes in the available metabolic intermediates in the invaded host cell.
In the second part of this study, we characterized known T3SS2 effector VPA1380 and discovered that VPA1380 localized to the host mitochondria by its N-terminal domain. By expressing untagged VPA1380 in yeast, we found that VPA1380 causes mitochondrial fragmentation in an activity-dependent manner. Tools were developed for use in future studies to elucidate host targets for VPA1380.
Collectively, we report the first demonstration of kinase activity for any VopG-like effector. We provide evidence for the mitochondrial localization of VPA1328 and VPA1380. Our findings support a role for VPA1328 in altering eukaryotic mitochondrial respiration and metabolism and a possible role for VPA1380 in altering mitochondrial morphology. The results of this study will aid future work to define how Vibrio parahaemolyticus exploits the host mitochondria in invaded human cells
Altered Vulvar Microbiomes in Vulvar Lichen Sclerosus
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.BACKGROUND: Vulvar lichen sclerosus (VLS) is a chronic and progressive dermatosis that most commonly affects the anogenital region of postmenopausal women. VLS etiology is incompletely understood, though a role for immune system dysregulation has been suggested given associations with autoimmune disease. The skin microbiome plays an important role in cutaneous immune function and may contribute to VLS pathogenesis or expression.
OBJECTIVE: In this prospective, longitudinal study, we investigated the association between bacterial and fungal microbiomes at the vulva and vagina in patients with VLS.
METHODS: First, we recruited postmenopausal women with a clinical diagnosis of VLS and healthy postmenopausal controls from the same general population. Experimental samples were obtained from the clitoral hood, interlabial sulcus, labia minora, perineum, and vagina. Additionally, patients with VLS were re-sampled 10-14 weeks after once-daily treatment with ultrapotent topical corticosteroid. Negative control samples of the clinical sampling environment were obtained with each encounter. Microbial DNA was extracted from samples. Bacterial and fungal libraries were prepared with primer sets targeting the 16S V1-V3 and ITS1 regions respectively. These libraries were sequenced at the UT Southwestern Genomics Core. QIIME2 with a divisive amplicon denoising algorithm 2 (DADA2) pipeline was used to process and analyze sequences. Shannon index was used to quantify alpha diversity. Unweighted UniFrac (bacteria) and Bray-Curtis dissimilarity (fungi) were used to quantify beta diversity. Relative abundance testing was performed at sites with significant community structural alterations using Linear discriminant analysis Effect Size (LEFSE) based on disease status. Pairwise difference and distance comparisons were used to evaluate changes in bacterial alpha and beta diversity with treatment. A supervised learning classifier was used to determine whether disease status could be predicted as a function of baseline vulvar bacterial microbiome composition.
RESULTS: A total of six subjects with VLS and twelve healthy postmenopausal controls were enrolled. Bacterial analysis at the community level revealed a loss of alpha diversity at each site analyzed; this loss was significant at the interlabial sulcus (p = 0.030, Kruskal-Wallis). Commensal bacteria including Staphylococcus epidermidis, Lactobacillus gasseri, and Lactobacillus jensenii were of significantly higher relative abundance in the control group (LEFSE) at this site. Longitudinal analysis of bacterial community diversity after treatment revealed the greatest recovery of alpha diversity at the interlabial sulcus. Supervised learning with a random forest classifier on bacterial vulvar data revealed an accuracy of 0.923 to predict disease status and redemonstrated several amplicon sequence variants including Staphylococcus epidermidis to be important in this prediction.
CONCLUSIONS: Taken together, we identified significant alterations in the diversity and composition of skin bacterial communities in VLS that are dependent on anatomic location. We also demonstrated indicators of disease status using machine learning techniques. Altogether, findings support a relationship between the skin microbiome and VLS and underscore the potential for the skin microbiome to serve as a non-invasive biomarker of disease