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2025

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Promotion Of Hiv Clearance By Sensitization Of Hiv Reservoirs To Cell Death, Min Li, Baichao Sun, Jing Dong, Jian-Rong Li, Laurie J Minze, Min Chen, Chao Cheng, Jin Wang Jan 2025

Promotion Of Hiv Clearance By Sensitization Of Hiv Reservoirs To Cell Death, Min Li, Baichao Sun, Jing Dong, Jian-Rong Li, Laurie J Minze, Min Chen, Chao Cheng, Jin Wang

Faculty, Staff and Students Publications

Introduction: HIV integrates its proviral DNA into the host genome to establish persistent infection. To promote HIV clearance, we have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. SECH approach can clear HIV-infected cells in approximately 50% humanized mice. However, the mechanisms for the resistance of reservoirs to depletion in mice with failure in HIV clearance are unclear.

Methods: We have performed single cell transcriptome analyses of HIV-infected T cells that escaped the treatments, in order to identify cellular pathways that could be targeted to …


Inhibition Of Ribosome Biogenesis In Vivo Causes P53-Dependent Death And P53-Independent Dysfunction, Charles J Cho, Thanh Nguyen, Amala K Rougeau, Yang-Zhe Huang, Sarah To, Xiaobo Lin, Supuni Thalalla Gamage, Jordan L Meier, Jason C Mills Jan 2025

Inhibition Of Ribosome Biogenesis In Vivo Causes P53-Dependent Death And P53-Independent Dysfunction, Charles J Cho, Thanh Nguyen, Amala K Rougeau, Yang-Zhe Huang, Sarah To, Xiaobo Lin, Supuni Thalalla Gamage, Jordan L Meier, Jason C Mills

Faculty, Staff and Students Publications

Background & aims: Although it is well-known that ribosomes are critical for cell function, and their synthesis (known as ribosome biogenesis [RiBi]) is energy-intensive, surprisingly little is known about RiBi in vivo in adult tissue.

Methods: Using a mouse model with conditional deletion of Nat10, an essential gene for RiBi and subsequent translation of mRNA, we investigated the effects of RiBi blockade in vivo, with a focus on pancreatic acinar cells during homeostasis and tumorigenesis.

Results: We observed an unexpected latency of several weeks between Nat10 deletion and onset of structural and functional abnormalities and p53-dependent acinar cell death. Although …


Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici Jan 2025

Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici

Faculty, Staff and Students Publications

Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …


Dual Inhibitor Of Mdm2 And Nfat1 For Experimental Therapy Of Breast Cancer: In Vitro And In Vivo Anticancer Activities And Newly Discovered Effects On Cancer Metabolic Pathways, Wei Wang, Marlene Aguilar, Sayantap Datta, Abigail Alley, Meheret Tadesse, Xinshi Wang, Xia Gao, Ruiwen Zhang Jan 2025

Dual Inhibitor Of Mdm2 And Nfat1 For Experimental Therapy Of Breast Cancer: In Vitro And In Vivo Anticancer Activities And Newly Discovered Effects On Cancer Metabolic Pathways, Wei Wang, Marlene Aguilar, Sayantap Datta, Abigail Alley, Meheret Tadesse, Xinshi Wang, Xia Gao, Ruiwen Zhang

Faculty, Staff and Students Publications

INTRODUCTION: The oncogene MDM2 has garnered attention not only for its role in cancer as a negative regulator of the tumor suppressor p53 but also for its p53-independent oncogenic activities. MDM2 also involves metabolic reprogramming, such as serine metabolism, respiration, mitochondrial functions, the folate cycle, and redox balance. Traditional MDM2 inhibitors blocking the protein-protein binding between MDM2 and p53 have shown limited clinical success in various stages of clinical trials, most likely due to low efficacy, drug toxicity, and drug resistance, highlighting the need for a novel, p53-independent strategy to inhibit MDM2. The present study investigated the antitumor effects of …


Proteomic Characterization And Comparison Of The Infective And Adult Life Stage Secretomes From Necator Americanus And Ancylostoma Ceylanicum, Yide Wong, Bruce A Rosa, Luke Becker, Mali Camberis, Graham Legros, Bin Zhan, Maria Elena Bottazzi, Ricardo T Fujiwara, Edita Ritmejeryte, Thewarach Laha, Sujittra Chaiyadet, Piyanan Taweethavonsawat, Paul J Brindley, Bethany K Bracken, Paul R Giacomin, Makedonka Mitreva, Alex Loukas Jan 2025

Proteomic Characterization And Comparison Of The Infective And Adult Life Stage Secretomes From Necator Americanus And Ancylostoma Ceylanicum, Yide Wong, Bruce A Rosa, Luke Becker, Mali Camberis, Graham Legros, Bin Zhan, Maria Elena Bottazzi, Ricardo T Fujiwara, Edita Ritmejeryte, Thewarach Laha, Sujittra Chaiyadet, Piyanan Taweethavonsawat, Paul J Brindley, Bethany K Bracken, Paul R Giacomin, Makedonka Mitreva, Alex Loukas

Faculty, Staff and Students Publications

More than 470 million people globally are infected with the hookworms Ancylostoma ceylanicum and Necator americanus, resulting in an annual loss of 2.1 to 4 million disability-adjusted-life-years. Current infection management approaches are limited by modest drug efficacy, the costs associated with frequent mass drug administration campaigns, and the risk of reinfection and burgeoning drug resistance. Subunit vaccines based on proteins excreted and secreted (ES) by hookworms that reduce worm numbers and associated disease burden are a promising management strategy to overcome these limitations. However, studies on the ES proteomes of hookworms have mainly described proteins from the adult life stage …


Use Of A Mouse Model For The Isolation Of Borrelia Puertoricensis From Soft Ticks, Edwin Vázquez-Guerrero, Alexander R Kneubehl, Guadalupe C Reyes-Solís, Carlos Machain-Williams, Aparna Krishnavajhala, Paulina Estrada-De Los Santos, Job E Lopez, José Antonio Ibarra Jan 2025

Use Of A Mouse Model For The Isolation Of Borrelia Puertoricensis From Soft Ticks, Edwin Vázquez-Guerrero, Alexander R Kneubehl, Guadalupe C Reyes-Solís, Carlos Machain-Williams, Aparna Krishnavajhala, Paulina Estrada-De Los Santos, Job E Lopez, José Antonio Ibarra

Faculty, Staff and Students Publications

The isolation of tick-borne relapsing fever (TBRF) spirochetes has proven to be a useful tool to understand their distribution in geographic areas where the tick vectors inhabit. However, their isolation and culture are not easy and in general an animal model is needed to achieve this task. Here, argasid ticks were collected from a neighborhood in Ciudad Caucel, and they were identified as Ornithodoros (Alectorobius) puertoricensis. To determine whether these were infected with TBRF bacteria they were fed with healthy mice but only a low burden of spirochetes was observed. An immunosuppressed mouse model was used to feed the ticks …


A Multifunctional Theranostic Ultrasound Platform For Remote Magnetogenetics And Expanded Blood-Brain Barrier Opening, Alec J Batts, Fotios N Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha L Gorman, Deny Tsakri, Rebecca L Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T Robinson, Elisa E Konofagou Jan 2025

A Multifunctional Theranostic Ultrasound Platform For Remote Magnetogenetics And Expanded Blood-Brain Barrier Opening, Alec J Batts, Fotios N Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha L Gorman, Deny Tsakri, Rebecca L Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T Robinson, Elisa E Konofagou

Faculty, Staff and Students Publications

Introduction: Brain stimulation techniques are critical for unraveling the innerworkings of complex neuronal pathways governing both normal physiological function and pathologic states in neurological disorders. Focused ultrasound (FUS) is an emerging technique poised to significantly alter central nervous system (CNS) drug delivery and neuroscience research through non-invasive means. Magnetogenetics is a brain stimulation technique which may benefit from FUS technology in that alternating magnetic fields (AMF), like FUS, can pass through the skull without requiring surgery.

Methodology: Magnetogenetics involves the deposition of superparamagnetic iron-oxide nanoparticles (SPIONs) and overexpression of thermoreceptor transmembrane proteins (e.g. TRPV1 and TRPA1) in the brain. When …


Establishing Standardized Transthoracic Echocardiography Reference Ranges For Mouse Models: Insights Into The Impact Of Anesthesia, Sex, And Age, Manuela A Oestereicher, Christopher S Ward, Elida Schneltzer, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Ghina Bou About, Mohammed Selloum, Hamid Meziane, Michelle Stewart, Lydia Teboul, Clare Norris, Dale Pimm, Marina Kan, Federico López Gómez, Robert Wilson, Mayra Monroy, Sheraz Pasha, Eva Zabrodska, Jan Prochazka, David Pajuelo Reguera, Zuzana Nichtova, Yann Herault, Sara Wells, Helen Parkinson, Jason D Heaney, Radislav Sedlacek, Xiang Gao, Martin Hrabe De Angelis, Nadine Spielmann Jan 2025

Establishing Standardized Transthoracic Echocardiography Reference Ranges For Mouse Models: Insights Into The Impact Of Anesthesia, Sex, And Age, Manuela A Oestereicher, Christopher S Ward, Elida Schneltzer, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Ghina Bou About, Mohammed Selloum, Hamid Meziane, Michelle Stewart, Lydia Teboul, Clare Norris, Dale Pimm, Marina Kan, Federico López Gómez, Robert Wilson, Mayra Monroy, Sheraz Pasha, Eva Zabrodska, Jan Prochazka, David Pajuelo Reguera, Zuzana Nichtova, Yann Herault, Sara Wells, Helen Parkinson, Jason D Heaney, Radislav Sedlacek, Xiang Gao, Martin Hrabe De Angelis, Nadine Spielmann

Faculty, Staff and Students Publications

Introduction: Mouse models play a critical role in cardiology research, offering valuable insights into the molecular mechanisms, genetics, and potential treatments for cardiovascular diseases. However, the ability to transfer findings in mice between studies is limited by the absence of standardized protocols and valid reference values for the assessment of normal cardiac function in mice. This study aims to establish comprehensive transthoracic echocardiography (TTE) reference ranges for mice, particularly focusing on C57BL/6N wild-type controls.

Methods: The study, which includes data from over 15,000 mice through the International Mouse Phenotyping Consortium (IMPC), highlights how variables such as sex, age, body weight, …


Exercise Mitigates High-Fat Diet-Induced Cardiac Dysfunction Via Apoe Genotype- And Immune-Dependent Mechanisms: A Photon-Counting Ct Study In Adult Mice, Rohan Nadkarni, Alex J Allphin, Darin P Clark, Yi Qi, Zay Yar Han, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea Jan 2025

Exercise Mitigates High-Fat Diet-Induced Cardiac Dysfunction Via Apoe Genotype- And Immune-Dependent Mechanisms: A Photon-Counting Ct Study In Adult Mice, Rohan Nadkarni, Alex J Allphin, Darin P Clark, Yi Qi, Zay Yar Han, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular dysfunction frequently accompanies aging and is often worsened by adverse lifestyle factors and genetic susceptibility. The apolipoprotein E (APOE) gene modulates susceptibility to cardiovascular disease, but how exercise and diet interact with APOE genotype remains insufficiently understood. We investigate the cardioprotective potential of exercise in humanized APOE-targeted replacement mice on control and high-fat diet, using photon-counting computed tomography (PCCT) and deep learning-based image segmentation.

Methods: This study included 251 male and female mice in mid-to-late life of APOE2, APOE3, and APOE4 genotypes with variation in humanized NOS2 (HN) mediated innate immune response, exercise status (exercised vs. sedentary) and …


Structural Dynamics And Binding Of Caenorhabditis Elegans Lifespan-Extending Lipid Binding Protein-3 To Polyunsaturated Fatty Acids, André R Cuevas, Matthew C Tillman, Meng C Wang, Eric A Ortlund Jan 2025

Structural Dynamics And Binding Of Caenorhabditis Elegans Lifespan-Extending Lipid Binding Protein-3 To Polyunsaturated Fatty Acids, André R Cuevas, Matthew C Tillman, Meng C Wang, Eric A Ortlund

Faculty, Staff and Students Publications

Intracellular lipid binding proteins (iLBPs) play crucial roles in lipid transport and cellular metabolism across the animal kingdom. Recently, a fat‐to‐neuron axis was described in Caenorhabditis elegans, in which lysosomal activity in the fat liberates polyunsaturated fatty acids (PUFAs) that signal to neurons and extend lifespan with durable fecundity. In this study, we investigate the structure and binding mechanisms of a lifespan‐extending lipid chaperone, lipid binding protein‐3 (LBP‐3), which shuttles dihomo‐γ‐linolenic (DGLA) acid from intestinal fat to neurons. We present the first high‐resolution crystal structure of LBP‐3, which reveals a classic iLBP fold with an unexpected and unique homodimeric …


Ai-Based Detection Of Coronary Artery Occlusion Using Acoustic Biomarkers Before And After Stent Placement, David Anderson Lloyd, Andrei Dragomir, Bulent Ozpolat, Biykem Bozkurt, Yasemin Akay, Metin Akay Jan 2025

Ai-Based Detection Of Coronary Artery Occlusion Using Acoustic Biomarkers Before And After Stent Placement, David Anderson Lloyd, Andrei Dragomir, Bulent Ozpolat, Biykem Bozkurt, Yasemin Akay, Metin Akay

Faculty, Staff and Students Publications

No abstract provided.


Revisiting Icd Therapy For Primary Prevention In Patients With Heart Failure And Reduced Ejection Fraction., Amin Yehya, Jose L Batista, Andrew J Sauer, Jonathan D Davis, Nasrien E Ibrahim, Roderick Tung, Biykem Bozkurt, Gregg C Fonarow, Sana M Al-Khatib Jan 2025

Revisiting Icd Therapy For Primary Prevention In Patients With Heart Failure And Reduced Ejection Fraction., Amin Yehya, Jose L Batista, Andrew J Sauer, Jonathan D Davis, Nasrien E Ibrahim, Roderick Tung, Biykem Bozkurt, Gregg C Fonarow, Sana M Al-Khatib

Faculty, Staff and Students Publications

Implantable cardioverter-defibrillators (ICDs) are recommended to reduce the risk of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF). The landmark studies leading to the current guideline recommendations preceded the 4 pillars of guideline-directed medical therapies (GDMTs). Therefore, some have questioned the role of ICDs for primary prevention in current clinical practice. In this paper, the authors provide an overview of the current ICD recommendations, including the instrumental clinical trials, the risk of SCD as observed in clinical trials vs real-world scenarios, disparities in ICD use among different patient populations, the impact of contemporary GDMT …


Stent Thrombosis: A Contemporary Guide To Definitions, Risk Factors, And Management, Ambre Flowers, Bernard Evenhuis, Benjamin Gabanic, Allison Weiss, Scott Eisenberg, Riyan Siddiqui, Affan Rizwan, Iqra Riaz, Hafeez Ul Hassan Virk, Mahboob Alam, Muzamil Khawaja, Markus Strauss, Chayakrit Krittanawong Jan 2025

Stent Thrombosis: A Contemporary Guide To Definitions, Risk Factors, And Management, Ambre Flowers, Bernard Evenhuis, Benjamin Gabanic, Allison Weiss, Scott Eisenberg, Riyan Siddiqui, Affan Rizwan, Iqra Riaz, Hafeez Ul Hassan Virk, Mahboob Alam, Muzamil Khawaja, Markus Strauss, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Stent thrombosis remains a major complication following percutaneous coronary intervention, with significant morbidity and mortality implications. Despite advancements in drug-eluting stents and optimized pharmacotherapy, real-world registry data indicate that definite or probable stent thrombosis occurs in approximately 0.5% of percutaneous coronary intervention cases, with a 30-day mortality rate approaching 25% and a long-term risk exceeding 30% at 10 years. Stent thrombosis is classified based on timing into acute, subacute, late, and very late thrombosis, with subacute and very late stent thrombosis being the most prevalent. Clinical consequences include myocardial infarction, emergent revascularization, and heightened cardiovascular risk, necessitating timely recognition and …


Finite Element Modeling In Obstetrics And Gynecology: Advances, Applications, And Challenges, Taylor Moseley, Ashley J Hicks, Elizabeth M Cosgriff-Hernandez, Manuel Karl Rausch, Julie Hakim Jan 2025

Finite Element Modeling In Obstetrics And Gynecology: Advances, Applications, And Challenges, Taylor Moseley, Ashley J Hicks, Elizabeth M Cosgriff-Hernandez, Manuel Karl Rausch, Julie Hakim

Faculty, Staff and Students Publications

Finite element modeling (FEM) is a critical tool in biomechanics and biomedical engineering, offering valuable insights where in vivo or ex vivo investigations are not possible. This review specifically highlights the diverse applications of FEM within obstetrics and gynecology through a comprehensive analysis of the literature. We explore the past use of FEM in analyzing complications affecting pelvic floor structures, urinary continence, and reproduction. The potential contributions of FEM in addressing these challenges are summarized and future directions for its application in obstetrics and gynecology are highlighted.


Recovery Of Iron And Aluminum From Acid Mine Drainage For Beneficial Uses, Katelyn Renee Pepe Jan 2025

Recovery Of Iron And Aluminum From Acid Mine Drainage For Beneficial Uses, Katelyn Renee Pepe

Graduate Theses, Dissertations, and Problem Reports (ETD)

Acid mine drainage (AMD) is a widespread issue across the globe, in which some of the most critical cases are created by the mining industry. Researchers have investigated ways to derive benefits from AMD, such as precipitating rare earth elements (REEs) to generate potential revenue from AMD treatment and supplement market demand. However, the bulk of precipitated sludge is composed of iron and aluminum, which also have market value but are discarded in current practice.

Using the Omega site in West Virginia (WV) as a representative AMD source, the objectives of this study are (1) to determine a replicable precipitation …


Screening Herbicides For Use In Newly Established Short Rotation Coppice Shrub Willow Plantations, Alex Thomas Smith Jan 2025

Screening Herbicides For Use In Newly Established Short Rotation Coppice Shrub Willow Plantations, Alex Thomas Smith

Graduate Theses, Dissertations, and Problem Reports (ETD)

A major setback for the establishment of short rotation coppice willow plantations is the control of competition from weeds. Weed competition has been found to cause increased mortality which lowers biomass yields when left uncontrolled. Mechanical weed control methods are the most used method of weed control, but their use can be complicated by cost, labor availability and site topography. Chemical weed control is also complicated by the fact that willow species are particularly sensitive to herbicides. Across three trials, we screen 11 herbicides for their potential to control weeds without significantly decreasing the vertical growth of willow trees. This …


A Comprehensive Uhplc-Ms/Ms And Extraction Method Reveals Flavonoid Profile And Concentration Are Diverse In Spinach (Spinacia Oleracea L), Michael P Dzakovich, Elaine A Le, Alvin L Tak, Shaji K Chacko Jan 2025

A Comprehensive Uhplc-Ms/Ms And Extraction Method Reveals Flavonoid Profile And Concentration Are Diverse In Spinach (Spinacia Oleracea L), Michael P Dzakovich, Elaine A Le, Alvin L Tak, Shaji K Chacko

Children’s Nutrition Research Center Staff Publications

INTRODUCTION: Spinach produces an array of unique flavonoids not commonly found in other fruits and vegetables. These molecules likely serve as defense agents against biotic and abiotic stress and may have health beneficial properties for humans. Current methods to analyze spinach flavonoids are incomplete and only capture a portion of this uncharacterized pathway. A comprehensive analysis method is needed to determine how genetics, environmental conditions, and other factors influence spinach flavonoid biosynthesis.

METHODS: We developed and validated a high-throughput extraction and ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method to separate and quantify 39 spinach flavonoid species in 11.5 …


Igf-1 Impacts Neocortical Interneuron Connectivity In Epileptic Spasm Generation And Resolution, Carlos J Ballester-Rosado, John T Le, Trang T Lam, Anne E Anderson, James D Frost, John W Swann Jan 2025

Igf-1 Impacts Neocortical Interneuron Connectivity In Epileptic Spasm Generation And Resolution, Carlos J Ballester-Rosado, John T Le, Trang T Lam, Anne E Anderson, James D Frost, John W Swann

Faculty, Staff and Students Publications

Little is known about the mechanisms that generate epileptic spasms following perinatal brain injury. Recent studies have implicated reduced levels of Insulin-like Growth Factor 1 (IGF-1) in these patients' brains. Other studies have reported low levels of the inhibitory neurotransmitter, GABA. In the TTX brain injury model of epileptic spasms, we undertook experiments to evaluate the impact of IGF-1 deficiencies on neocortical interneurons and their role in spasms. Quantitative immunohistochemical analyses revealed that neocortical interneurons that express glutamic acid decarboxylase, parvalbumin, or synaptotagmin 2 co-express IGF-1. In epileptic rats, expression of these three interneuron markers were reduced in the neocortex. …


Survey And Improvement Strategies For Gene Prioritization With Large Language Models, Matthew B Neeley, Guantong Qi, Guanchu Wang, Ruixiang Tang, Dongxue Mao, Chaozhong Liu, Sasidhar Pasupuleti, Bo Yuan, Fan Xia, Pengfei Liu, Zhandong Liu, Xia Hu Jan 2025

Survey And Improvement Strategies For Gene Prioritization With Large Language Models, Matthew B Neeley, Guantong Qi, Guanchu Wang, Ruixiang Tang, Dongxue Mao, Chaozhong Liu, Sasidhar Pasupuleti, Bo Yuan, Fan Xia, Pengfei Liu, Zhandong Liu, Xia Hu

Duncan NRI Faculty and Staff Publications

Motivation: Rare diseases remain difficult to diagnose due to limited patient data and genetic diversity, with many cases remaining undiagnosed despite advances in variant prioritization tools. While large language models have shown promise in medical applications, their optimal application for trustworthy and accurate gene prioritization downstream of modern prioritization tools has not been systematically evaluated.

Results: We benchmarked various language models for gene prioritization using multi-agent and Human Phenotype Ontology classification approaches to categorize patient cases by phenotype-based solvability levels. To address language model limitations in ranking large gene sets, we implemented a divide-and-conquer strategy with mini-batching and token limiting …


Zic1 Is A Context-Dependent Medulloblastoma Driver In The Rhombic Lip, John J Y Lee, Ran Tao, Zhen You, Parthiv Haldipur, Anders W Erickson, Hamza Farooq, Liam D Hendriske, Namal Abeysundara, Cory M Richman, Evan Y Wang, Neha Das Gupta, Jennifer Hadley, Melissa Batts, Christopher W Mount, Xiaochong Wu, Alex Rasnitsyn, Swneke Bailey, Florence M G Cavalli, Sorana Morrissy, Livia Garzia, Kulandaimanuvel Antony Michealraj, Abhi Visvanathan, Vernon Fong, Jonelle Palotta, Raul Suarez, Bryn G Livingston, Miao Liu, Betty Luu, Craig Daniels, James Loukides, Anne Bendel, Pim J French, Johan M Kros, Andrey Korshunov, Marcel Kool, Fernando Chico Ponce De León, Mario Perezpeña-Diazconti, Boleslaw Lach, Sheila K Singh, Sarah E S Leary, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji-Yeoun Lee, Teiji Tominaga, William A Weiss, Joanna J Phillips, Shizhong Dai, Gelareh Zadeh, Ali G Saad, László Bognár, Almos Klekner, Ian F Pollack, Ronald L Hamilton, Young-Shin Ra, Wieslawa A Grajkowska, Marta Perek-Polnik, Reid C Thompson, Anna M Kenney, Michael K Cooper, Stephen C Mack, Nada Jabado, Mathieu Lupien, Marco Gallo, Vijay Ramaswamy, Mario L Suva, Hiromichi Suzuki, Kathleen J Millen, L Frank Huang, Paul A Northcott, Michael D Taylor Jan 2025

Zic1 Is A Context-Dependent Medulloblastoma Driver In The Rhombic Lip, John J Y Lee, Ran Tao, Zhen You, Parthiv Haldipur, Anders W Erickson, Hamza Farooq, Liam D Hendriske, Namal Abeysundara, Cory M Richman, Evan Y Wang, Neha Das Gupta, Jennifer Hadley, Melissa Batts, Christopher W Mount, Xiaochong Wu, Alex Rasnitsyn, Swneke Bailey, Florence M G Cavalli, Sorana Morrissy, Livia Garzia, Kulandaimanuvel Antony Michealraj, Abhi Visvanathan, Vernon Fong, Jonelle Palotta, Raul Suarez, Bryn G Livingston, Miao Liu, Betty Luu, Craig Daniels, James Loukides, Anne Bendel, Pim J French, Johan M Kros, Andrey Korshunov, Marcel Kool, Fernando Chico Ponce De León, Mario Perezpeña-Diazconti, Boleslaw Lach, Sheila K Singh, Sarah E S Leary, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji-Yeoun Lee, Teiji Tominaga, William A Weiss, Joanna J Phillips, Shizhong Dai, Gelareh Zadeh, Ali G Saad, László Bognár, Almos Klekner, Ian F Pollack, Ronald L Hamilton, Young-Shin Ra, Wieslawa A Grajkowska, Marta Perek-Polnik, Reid C Thompson, Anna M Kenney, Michael K Cooper, Stephen C Mack, Nada Jabado, Mathieu Lupien, Marco Gallo, Vijay Ramaswamy, Mario L Suva, Hiromichi Suzuki, Kathleen J Millen, L Frank Huang, Paul A Northcott, Michael D Taylor

Faculty, Staff and Students Publications

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma). Overexpression of ZIC1 suppresses the growth of group 3 medulloblastoma models, whereas it promotes the proliferation of SHH medulloblastoma precursor cells. SHH medulloblastoma ZIC1 mutants show increased activity versus wild-type ZIC1, whereas G4 medulloblastoma …


Natural Capital Credit Risk Assessment In Agricultural Lending: An Approach Based On The Natural Capital Protocol, Francisco Ascui, Theodor Florian Cojoianu Jan 2025

Natural Capital Credit Risk Assessment In Agricultural Lending: An Approach Based On The Natural Capital Protocol, Francisco Ascui, Theodor Florian Cojoianu

Research Collection College of Integrative Studies

It is increasingly recognised that financial institutions have significant impacts and dependencies on natural capital – defined as the stock of the world’s renewable and non-renewable natural resources and ecosystems that yield flows of environmental goods and services, which directly and indirectly underpin the global economy and human wellbeing. Historically, many of these impacts and dependencies have been overlooked. The value of goods and services that nature provides ‘for free’ has often been ignored, and resources have typically been priced at their cost of extraction, rather than the cost of their replacement or substitution, which would promote more sustainable long-term …


The Climate-Biodiversity-Pollution Nexus: The Pricing Of Environmental Credit Risks For European Industrial Polluters, Dominik Hirschbühl, Andrej Ceglar, Theodor Cojoianu, Tina Emambakhsh, Yifan Qi, Caterina Rho, Elsie Hu, Marco Petracco, Fabrizio Biganzoli, Alfred De Jager, Laura Garcia Herrero, Andrea Mandrici, Carlo Pasqua Jan 2025

The Climate-Biodiversity-Pollution Nexus: The Pricing Of Environmental Credit Risks For European Industrial Polluters, Dominik Hirschbühl, Andrej Ceglar, Theodor Cojoianu, Tina Emambakhsh, Yifan Qi, Caterina Rho, Elsie Hu, Marco Petracco, Fabrizio Biganzoli, Alfred De Jager, Laura Garcia Herrero, Andrea Mandrici, Carlo Pasqua

Research Collection College of Integrative Studies

This study examines how euro area banks factor pollution-induced biodiversity risks into lending decisions, using data from 832 banks and 5,000 major polluters. Our results show that banks are increasingly pricing these risks by adjusting loan-to-value ratios and interest rates. Banks adjust lending conditions in line with EU pollution and biodiversity protection legislation, particularly for companies with large pollution footprints near biodiversity-protected areas or those contributing to Environmental Quality Standards failures of downstream surface waters. The former is driven primarily by banks’ adoption of biodiversity policies and public commitments to the Equator Principles, while the latter is a result of …


Landscapes Of State Capitalism: Reconciling The Vernacular, National Development Imaginaries, And Green Capital Accumulation, Sol Andrew Stokols Jan 2025

Landscapes Of State Capitalism: Reconciling The Vernacular, National Development Imaginaries, And Green Capital Accumulation, Sol Andrew Stokols

Research Collection College of Integrative Studies

This article theorizes ‘state capitalist landscapes’ as a unique spatial form shaped by state-owned developers that reconcile economic goals with national development imperatives and symbolic national imaginaries. State capitalist landscapes, I argue, integrate economically productive spaces with natural spaces to symbolize imaginaries of the nation. Through an inductive case study methodology, this article surveys three industrial zones developed and/or under development by state owned developers: Singapore's Jurong, China's Xiong’an New Area, and Thailand's Wangchan Valley. In each of these cases, natural landscapes are integrated into new economic zones in order to construct specific symbolic and/or political imaginaries of the nation: …


Rubber Wars: Rubber At The End Of Empire In Colonial Malaya, C. 1945–57, Fiona Williamson Jan 2025

Rubber Wars: Rubber At The End Of Empire In Colonial Malaya, C. 1945–57, Fiona Williamson

Research Collection College of Integrative Studies

This article argues the Malayan rubber industry’s fortunes both reflected and coloured the relationship between Britain and the USA during the early Cold War era. British Malaya had developed a world leading rubber industry within a few short decades. The importance of rubber to burgeoning manufacturing and transport industries however – especially in the United States – meant that the commodity became caught up in the geopolitics of a changing world order. During the 1920s and 1930s, Britain had dictated international market rules due to their largely unrivalled position but the Second World War had changed the global balance of …


Mombyry Guive. Desde Muy Lejos (2025), María Camila Solalinde Melgarejo Jan 2025

Mombyry Guive. Desde Muy Lejos (2025), María Camila Solalinde Melgarejo

Grado en Diseño de Moda

Este proyecto de final de grado se centra en la creación de una marca personal basada en la comparación de la influencia española en la vestimenta paraguaya en el siglo XVIII. La investigación se enfoca en como la moda de la época llega a trascender lo estética, reflejando historia, valores e identidad incorporando aspectos tantos paraguayos como europeos, en este caso de España.

El proyecto pretende crear una colección en donde se reinterprete piezas tradicionales paraguayas femeninas fusionándolas con piezas de origen español, incluyendo figuras e influencias históricas de la época. Así también, se busca honrar la herencia compartida destacando …


Science, Physiology, And Nutrition For The Nonscientist, Judi S. Morrill Jan 2025

Science, Physiology, And Nutrition For The Nonscientist, Judi S. Morrill

Open Educational Resources

A wonderful blend of physiology, nutrition, biochemistry, genetics, biology, evolution, chemistry--what we all need to know as informed citizens. A basic knowledge of the life sciences and how our bodies work--to promote our own good health, especially as we're bombarded with misleading advertisements, soundbites, and the like. DNA fingerprinting, calorie requirements, dietary advice, genetic engineering (including gene editing with CRISPR cas9)--all in an easy-to understand book.


Realities Of Nutrition, Judi S. Morrill Jan 2025

Realities Of Nutrition, Judi S. Morrill

Open Educational Resources

What Is Nutrition Reality? Is it in the advertising claims that a food is natural or supplies instant energy? Is it in the myriad of dietary supplements? Is it in the diet plans for instant weight loss and glowing health? The only way to find out is to learn the basic principles of nutrition science, so you can be your own nutrition expert. Here is the true introduction to nutrition that you will read with pleasure and real understanding. It will free you from dependence on popular sources of information - often misinformation - so you can distinguish illusion from …


Words And Stardom: Modernist Poetic Responses To Asta Nielsen, Karl E. Toepfer Jan 2025

Words And Stardom: Modernist Poetic Responses To Asta Nielsen, Karl E. Toepfer

Open Educational Resources

This essay discusses how four modernist poets portrayed the Danish movie star Asta Nilesen (1881-1972). German Hans Schiebelhuth (1895-1944) describes the "demonic" power of Nielsen's image to awaken dark aspects of his adolscent personality. For the Flemish poet Paul van Ostaijen (1896-1928), Nielsen's cinematic image provokes a radical shattering of language into extravagant "word-images." Danish writer Rudolf Broby-Johansen (1900-1987) linked Nielsen's image to a radical (Marxist) critique of oppressive sexual politics within a capitalist society. German Franz Behrens (1895-1977) composed a lengthy, expressionist ode to Nielsen from the perspective of one who actually worked as a screenwriter in the German …


Dfcp1 Is A Regulator Of Starvation-Driven Atgl-Mediated Lipid Droplet Lipolysis, Victoria A Ismail, Meg Schuetz, Zak N Baker, Jean A Castillo-Badillo, Teri V Naismith, David J Pagliarini, David J Kast Jan 2025

Dfcp1 Is A Regulator Of Starvation-Driven Atgl-Mediated Lipid Droplet Lipolysis, Victoria A Ismail, Meg Schuetz, Zak N Baker, Jean A Castillo-Badillo, Teri V Naismith, David J Pagliarini, David J Kast

2020-Current year OA Pubs

Lipid droplets (LDs) are transient lipid storage organelles that can be readily tapped to resupply cells with energy or lipid building blocks, and therefore play a central role in cellular metabolism. Double FYVE Domain Containing Protein 1 (DFCP1/ZFYVE1) has emerged as a key regulator of LD metabolism, where the nucleotide-dependent accumulation of DFCP1 on LDs influences their size, number, and dynamics. Here we show that DFCP1 regulates lipid metabolism by directly modulating the activity of Adipose Triglyceride Lipase (ATGL/PNPLA2), the rate-limiting lipase driving the catabolism of LDs. We show through pharmacological inhibition of key enzymes associated with LD metabolism that …


Multisensory Naturalistic Decoding With High-Density Diffuse Optical Tomography, Kalyan Tripathy, Zachary E Markow, Morgan Fogarty, Mariel L Schroeder, Alexa M Svoboda, Adam T Eggebrecht, Bradley L Schlaggar, Jason W Trobaugh, Joseph P Culver Jan 2025

Multisensory Naturalistic Decoding With High-Density Diffuse Optical Tomography, Kalyan Tripathy, Zachary E Markow, Morgan Fogarty, Mariel L Schroeder, Alexa M Svoboda, Adam T Eggebrecht, Bradley L Schlaggar, Jason W Trobaugh, Joseph P Culver

2020-Current year OA Pubs

SIGNIFICANCE: Decoding naturalistic content from brain activity has important neuroscience and clinical implications. Information about visual scenes and intelligible speech has been decoded from cortical activity using functional magnetic resonance imaging (fMRI) and electrocorticography, but widespread applications are limited by the logistics of these technologies.

AIM: High-density diffuse optical tomography (HD-DOT) offers image quality approaching that of fMRI but with the silent, open scanning environment afforded by optical methods, thus opening the door to more naturalistic research and applications. Although early visual decoding studies with HD-DOT have been promising, decoding of naturalistic auditory and multisensory stimulus information from HD-DOT data …