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Beyond the Hills
Get PDFThe author submitted this entry in the Fictional Short Story category (Amateur division) for the 2024 On My Own Time (OMOT) Art Show.This work received a First Place Award in the "Fictional Short Story" category in the 2024 On My Own Time show.This piece was inspired by a recent patient of mine. It is the first story I have written that was directly motivated by a patient encounter
Investigating the Mechanism and Mode of Action of Golgi Toxins
Get PDFAuxin-inducible forward genetics uncovered point mutations within Golgi Brefeldin A Resistant Guanine Nucleotide Exchange Factor 1 or GBF1 following lethal dose selection with a synthetic disubstituted pyrimidine toxin called Golgitox (GTOX). Resistant clones were also cross-resistant to the fungal toxin, Brefeldin A (BFA), and synthetic GBF1 inhibitor, Golgicide A (GCA). Like BFA and GCA, GTOX triggered Golgi disassembly via GBF1. Given that BFA is a reported molecular glue, we profiled Gbf1-Arf interactions in 293T cell lysates pre-treated with Golgi toxin. Both GTOX and GCA promoted GBF1-dependent interactions with Arfs 4 and 5, whereas BFA also interacted with Arf1. GBF1 domain mapping revealed that the HUS-SEC7-HDS1 domains were sufficient for promoting GTOX-dependent engagement with Arfs 4 and 5. Meanwhile, structural activity relationship studies showed that modifying the methyl group on the benzimidazole ring preserved GTOX activity and interactions between Gbf1 and Arfs 4 and 5. To assess which Arfs regulate BFA and GTOX cytotoxicities, genome-wide CRISPR/Cas9 compound enrichment screens were carried out, which identified ARF4 as being the most enriched hit. Next, we validated that ARF4 loss-of-function partially confers resistance to BFA and GTOX. Next, we asked whether GTOX preferentially interacts with ARF4-GDP versus ARF4-GTP. We found that exogenous ARF4 T31N (GDP-locked mutant) sensitized HCT116 scramble control cells 4-fold to GTOX, interacted with Gbf1 just as well as WT Arf4, but failed to rescue Arf4-mediated BiP retrieval. Collectively, these results suggest that the Gbf1-GTOX-Arf4-GDP complex is functionally inactive but deleterious to cell viability. Taken together, GTOX may act as a molecular glue to suppress GBF1 functions through downstream effector substrates like Arfs 4 and 5
Branched Chain Amino Acid Metabolism in Development and Cancer
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.Dysregulation of branched chain amino acids (BCAAs) and/or the enzymes catalyzing the first step in their catabolism, branched chain amino acid transaminase (BCAT) 1 or 2, are associated with a multitude of diseases. Despite their importance in physiology and pathobiology, in vivo studies examining the roles of BCAT1 and BCAT2 in normal development and cancer are critically lacking. We generated new BCAT1 and/or BCAT2 constitutive or conditional knockout (KO) mice, as well as BCAT1 constitutive or conditional knockin overexpression (OE) mice, and systematically examined the impacts of BCAT1 and/or BCAT2 KO or BCAT1 OE on normal development, hematopoiesis, and leukemia initiation and maintenance in vivo.
First, we discovered that loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and BCKAs, causing morbidity and mortality that can be ameliorated by dietary BCAA restriction. Through proximity labeling proteomics, enzymatic and isotope tracing assays, we provide evidence for the formation of a mitochondrial BCAA metabolon involving BCAT2 and BCKDH, the second enzyme catalyzing the rate-limiting step of BCAA catabolism. Disabling the metabolon contributes to BCAT2-deficiency-induced phenotypes, which can be reversed by BCAT1-mediated BCKA reamination. These findings establish a role for metabolon formation in BCAA metabolism in vivo, and suggest a new strategy to modulate this pathway in diseases involving dysfunctional BCAA metabolism.
Next, we determined that BCAT1 is dispensable for normal hematopoiesis and development, but BCAT1 OE increases hematopoietic stem cell frequency and function. BCAT1 expression is significantly increased in human primary AML samples containing FLT3 and AML1-ETO mutations but decreased in AML with MLL abnormalities, raising a fundamental question about how distinct oncogenic drivers create selective metabolic dependencies. Using retroviral and genetic murine leukemia models, we discovered that BCAT1 is required for FLT3-ITD- and AE9a-induced leukemia development and FLT3-ITD leukemia maintenance, whereas BCAT1 OE accelerated FLT3-ITD leukemia progression. In contrast, modulating BCAT1 expression in MLL-AF9 had no effect on leukemia development or maintenance. Our findings establish BCAT1 and BCAA as a metabolic dependency of AML-initiating cells in vivo and uncover new insights into onco-genotype-specific metabolic rewiring as a selective and targetable vulnerability
Portal hypertension: evolving paradigms in diagnosis and care
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
Narrative Humility in Medical Education, Research, & Healthcare Delivery
No full textThis talk underscores the pivotal role of storytelling and active listening in fostering compassionate care for both patients and healthcare providers. This approach encourages individuals to cultivate essential skills such as self-awareness, reflection, imagination, empathy, curiosity, and emotional self-regulation. By drawing parallels with activities like reading, theater, music, and art, this approach prompts a deeper appreciation for the diverse narratives and perspectives encountered in healthcare. Additionally, emphasizing justice, equity, diversity and inclusion (JEDI) within this framework underscores the importance of recognizing and valuing the richness of human experiences. Medical librarians and other healthcare researchers might be inspired to enhance their search, analysis, and provision of critical information for patient care and physician well-being by incorporating such humanities-based approaches
Assessing Medical Student Information-Seeking Skills During a Residency Readiness Stimulation
Get PDFOBJECTIVE: This study aimed to assess the information-seeking skills of medical students participating in a Night-onCall simulation program, which evaluates students' preparedness for common clinical conditions and medical emergencies. METHODS: The Night-onCall experience exposes students to real-world clinical cases and takes place over several days. Librarians collaborated to evaluate the students' search strategies in real time for clinical scenarios, focusing on their use of evidence-based practice (EBP) principles and point-of-care tools. RESULTS: Students' searching behavior was recorded. Librarians observed and evaluated the students' search competency and provided feedback. Students were expected to employ EBP skills to solve clinical problems and make informed patient care decisions. The assessment included evaluating students' proficiency in using point-of-care resources for relevant information retrieval. CONCLUSION: The Night-onCall program's popularity has increased, allowing more students to participate. However, lack of clarity regarding how Night-onCall had been integrated with the medical school's curriculum made it challenging for librarians to assess students' preparedness. Future collaboration between librarians and Night-onCall administrators is recommended, as this would ensure students receive appropriate guidance and resources before the simulation and allow librarians to tailor their feedback to align evaluation methods with intended objectives
Engage and Include: Universal Design Meets Active Learning in Library Instruction
Get PDFOBJECTIVE: To prepare librarians to incorporate universal design and active learning strategies into one-shot library instruction sessions to enhance participant engagement and learning. METHODS: A team of librarians with backgrounds in K-12 education and academic librarianship designed a 1.5-hour professional development workshop for medical librarian colleagues on universal design and active learning. Various active learning techniques were introduced and demonstrated during the workshop, such as Tug of War, Jig Saw, and Muddiest Point. Instructional technology tools to facilitate active learning were also introduced. RESULTS: Attendees activated background knowledge, made deep connections, and collaborated more with peers. Librarians reported that they intended to utilize the strategies and tools introduced in subsequent library instruction sessions. CONCLUSIONS: An effective method for preparing librarians to incorporate universal design and active learning into their teaching is to demonstrate it and provide participants more than one way to learn. The use of active learning techniques in lessons significantly enhanced participant engagement, collaboration, and knowledge activation by creating a more positive, inclusive, and interactive learning environment
Current Issues in Evidence Synthesis
Get PDFThis will be a conversation on current topics in systematic reviews, such as databases to consider searching that are outside of the United States and western Europe, our responsibilities towards mitigating language bias in evidence synthesis and ways to do that, and possible current and future uses of artificial intelligence in systematic reviews, as well as ethical considerations and concerns regarding the technology
Exploring Evidence Synthesis Output
Get PDFOBJECTIVE: The library at a regional public R1 without a medical or veterinary school had provided informal and ad hoc support to evidence synthesis (ES). A clear understanding of the ES work being done would provide a basis for decision making. METHODS: We determined to use a mapping review framework to identify the scope of and trends in ES output of the institution. We conducted a comprehensive search for ES work published by affiliated researchers, screened in COVIDENCE and then extracted, analyzed, and visualized the data. RESULTS: We identified 382 published studies by affiliated researchers and charted them by type of ES, college or department affiliation, methodology, tools used, librarian involvement, and other factors. Our data shows an increase in the volume and type of ES work after 2012 and a greater diversity of discipline and ES type than predicted. Every college in the university was represented in our dataset. Librarians were not involved in most reviews. Most reviews at our university were not in the health sciences even though nursing is our largest college and a heavy user of ES resources. Additional analysis is forthcoming. CONCLUSIONS: Our understanding of ES work at out institution was incomplete. What we learned in this process will help us allocate resources better. Our previous understanding of need was based on requests that made it to a librarian for assistance and excluded the majority of ES work at our institution
Open Access Week Outreach and Collaboration Events
Get PDFBACKGROUND: LSU Health Sciences Center - New Orleans Libraries hosted outreach events during International Open Access Week in October 2023. We partnered with colleagues at Tulane School of Medicine Library to build and strengthen working relationships and expand the expert content offered to our institution. It was also an opportunity to raise the profile of the LSU Health Sciences Center - New Orleans Libraries within the institution and allow newly hired librarians and staff members to collaborate on a group project. Events were held throughout the week at both campuses of LSU Health- New Orleans. The events included open houses, an Open-Access themed Escape Room, hybrid presentations on Open Science themed topics, and a documentary viewing. A NNLM Exhibit Grant was used to fund the materials and activities. DESCRIPTION: The broad nature of International Open Access Week topics opened the possibility for partnering with health science librarians at a nearby medical school. The highlight of the collaboration was presentations on Open Science topics in a hybrid format to reach both institutions. The highlight of the outreach activities was a themed Escape Room for a hands-on in-person learning experience about Open Access publishing. CONCLUSION: The effort was successful in both the collaboration among new faculty and staff at LSU Health Sciences Center - New Orleans as well as strengthening the connection with Tulane School of Medicine librarians. Future events will focus on specific audiences and holding the events over a longer period of time. Opportunities to offer outreach events at both institutions will be explored