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Sex-Specific Differences In Mediobasal Hypothalamus In Response To Nutritional States, Jonathan C Bean, Jinjing Jian, Tzu-Chiao Lu, Hailan Liu, Kristine Conde, Darah A Threat, Sanika V Jossy, Megan E Burt, Jingjing Cheng, Yue Deng, Xing Fang, Xiaoyu Geng, Junying Han, Yongxiang Li, Hesong Liu, Qingzhuo Liu, Yutian Liu, Yuhan Shi, Longlong Tu, Mengjie Wang, Xu Xu, Yuxue Yang, Meng Yu, Xinming Liu, Meixin Sun, Fuhui Wang, Olivia Z Ginnard, Yongjie Yang, Yang He, Chunmei Wang, Yanyan Qi, Hongjie Li, Yong Xu

Children’s Nutrition Research Center Staff Publications

The arcuate nucleus of the hypothalamus plays a central role in sensing and integrating nutritional, hormonal, and neural signals that regulate feeding, energy homeostasis, growth, and reproduction, all of which show pronounced sex differences. However, the cellular mechanisms underlying these responses remain poorly understood. We performed snRNA-seq of the mediobasal hypothalamus, focusing on the arcuate nucleus, in female and male mice under different nutritional states. Analysis of 42 cell types revealed that Agrp neurons were most sensitive to nutritional changes, dopaminergic neurons showed strong sex-specific differences, and KNDy neurons were highly responsive to both sex and nutrition. Pomc neurons displayed …

Anti-Apoptotic Bcl-2 Binds To All Three Ip3r Isoforms, Thereby Limiting The Ca2+-Flux Properties Of Ip3r Homo-Tetramers, Ian De Ridder, Claire Cauwelier, Larry E Wagner Ii, Jens Loncke, Vikas Arige, Irina I Serysheva, David I Yule, Geert Bultynck

Faculty, Staff and Student Publications

Anti-apoptotic B-cell lymphoma 2 (BCL-2) controls inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca²+ signalling. As cells typically express all three IP3R isoforms in variable abundances that assemble in hetero-tetrameric channels, the specific effects of BCL-2 on each isoform remain unclear. Here, we employed a reductionist approach using HEK293 cells triple-IP3R knockout reconstituted with a single IP3R isoform to elucidate the impact of BCL-2 on Ca2+ signalling by homo-tetrameric IP3R channels. Co-immunoprecipitation experiments demonstrated that BCL-2 interacts with each IP3R isoform. Live-cell Ca²+ imaging revealed that BCL-2 overexpression suppresses Ca²+ signals evoked by any of the three IP3R isoforms. Moreover, BCL-2 overexpression impaired …

Recent Advances In The Pharmacological Properties Of Scutellarin: Mechanistic Insights And Therapeutic Potential, Hind A. Satar, Emad Yousif, Ahmed Ahmed, Muna Bufaroosha

AUIQ Complementary Biological System

Scutellarin, a flavonoid glycoside primarily derived from Scutellaria baicalensis, has garnered increasing scientific interest for its multifaceted pharmacological properties. This review summarizes recent advances in our understanding of scutellarin's therapeutic effects, including its antioxidant, anti-inflammatory, neuroprotective, cardioprotective and anticancer activities. Emphasis is placed on elucidating its molecular mechanisms of action, such as modulation of the NF-κB, Nrf2, and PI3K/Akt pathways, and its role in regulating oxidative stress, inflammation, and apoptosis. Additionally, we discuss formulation innovations, including nanoparticle and liposomal delivery systems, aimed at overcoming scutellarin's poor oral bioavailability and enhancing therapeutic performance. Key limitations in current research …

International Society Of Sports Nutrition Position Stand: Effects Of Dietary Antioxidants On Exercise And Sports Performance, Drew E. Gonzalez, Broderick L. Dickerson, Brandon M. Roberts, Jennifer A. Kurtz, Adam M. Gonzalez, Matthew J. Mcallister, Jeffrey L. Heileson, Richard J. Bloomer, Shawn M. Arent, Darren G. Candow, Jeffrey R. Stout, Karen A. Hecht, Bill Campbell, Chad M. Kerksick, Douglas Kalman, Jose Antoino, Richard B. Kreider

Faculty Publications

Following a comprehensive review, the International Society of Sports Nutrition (ISSN) has developed an official position on the role of dietary antioxidants in exercise and sport. Antioxidants play a complex, context-dependent role in vivo; they can facilitate recovery from exercise but may also hinder training adaptations when consumed at supraphysiological doses. While endogenous antioxidant systems can effectively maintain redox balance, dietary sources, particularly whole foods, can help mitigate excessive oxidative stress following intense/heavy training or inadequate recovery. The influence of dietary antioxidants depend on timing, dosage, type, and individual factors. The ISSN’s official position encompasses the following: (1) Redox balance …

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …

Ns5-Targeting Nucleoside Analogs Inhibit Dengue Virus And Other Flaviviruses, Priyanka Bhakt, Swechha Pokharel, Yue Li, Tamanna Srivastava, Jesse Miller, Mark Dittmar, Yongqing Zhu, David Nguyen, Zachary Walter, Kasirajan Ayyanathan, Matthew Tudor, Chenguang Yu, Arnab Chatterjee, Holly Ramage, David Schultz, Sara Cherry

Department of Microbiology and Immunology Faculty Papers

Dengue virus (DENV) is a mosquito-transmitted flavivirus that circulates globally as four distinct serotypes and poses a substantial threat to public health. There are an estimated ~96 million symptomatic infections yearly, including severe cases of dengue fever, underscoring the urgency of identifying effective therapeutics targeting all four serotypes. Nucleoside analogs, which mimic endogenous nucleosides to inhibit viral RNA replication, offer a promising strategy for broad-spectrum antiviral development. Here, we conducted a high-throughput screen of 1,101 nucleoside analogs against DENV serotype 2 (DENV2) in a panel of human cell models, including human epithelial cells, hepatocytes, and fibroblasts. Candidates that were active …

Tumor Microenvironment Transcriptional Activity Enables Robust Stratification Of Chemotherapy Response In Triple-Negative Breast Cancer, Yaoyi Dai, Xiaoxi Pan, Shuai Guo, Shuangxi Ji, Shaolong Cao, Matthew D Montierth, Yujie Jiang, Jeffrey T Chang, Leming Shi, Shabnam Shalapour, Gloria V Echeverria, Lucy Yates, Johan Staaf, Bora Lim, Yinyin Yuan, Wenyi Wang

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) exhibits heterogeneous treatment responses, yet molecular subtypes based on predefined biological pathways show limited prognostic value. We introduce tumor-specific total mRNA expression (TmS), a pathway-agnostic deconvolution metric derived from matched RNA/DNA sequencing, as a robust stratification tool. Analyzing 575 TNBC patients across Western and East Asian populations, TmS outperforms established subtypes in predicting chemotherapy outcomes, stratifying patients into high TmS with favorable prognosis and low TmS with poor prognosis. Stromal enrichment with immune exclusion emerges as a universal feature of chemotherapy-resistant low-TmS tumors across all cohorts. Population-specific features distinguish Asian cohorts: high-TmS tumors exhibit cell cycle-driven …

On-Orbit Correction Of Ecostress Radiances By Comparison With Iasi Hyperspectral Sounders, David S. Wethey, Sarah A. Woodin, Jorge Vazquez-Cuervo

Faculty Publications

Radiance data from ECOSTRESS (ECOsystem Spaceborne Thermal Radiometer Experiment on Space Station), which is the first of a planned virtual constellation of wide-swath ultra-high-resolution thermal satellites, were used to test the concept of on-orbit cross-calibration based on the Global Space-based Inter-Calibration System (GSICS) with the Infrared Atmospheric Sounding Interferometer (IASI) as the reference. Validation of the results was performed using comparisons of corrected ECOSTRESS radiances with strictly independent data from IASI and the Cross-Track Infrared Sounder (CrIS) and with RTTOV radiative transfer simulations of clear-sky observations in iQuam (the NOAA in situ sea surface temperature quality monitor database). ECOSTRESS has …

Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger

Faculty, Staff and Student Publications

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect …

Mutant Kras In Brain Endothelial Cells Promotes Vascular Inflammation And Impairs Vascular Integrity In Brain Arteriovenous Malformation, Jung-Eun Park, Bridger H Freeman, Hyejin Park, Sehee Kim, Adrian E Bafor, Ohnmar Myint, Song Gao, Zhen Xu, Jakob Körbelin, Jaroslaw Aronowski, Peng Roc Chen, Eunhee Kim, Eun S Park

Faculty, Staff and Student Publications

Somatic KRAS (KRASG12V) mutation in endothelial cells (EC) induces brain arteriovenous malformation (bAVM) that could lead to vascular instability and ultimately bleeding. However, the causes of bAVM instability remain unclear. Here we demonstrate that KRASG12V expressing cultured ECs (KRAS-G12V-EC) have increased expression of pro-inflammatory mediators and reduced expression of blood-brain-barrier (BBB) junction constituents. The conditioned medium from KRAS-G12V-EC can activate BV2-microglia (BV2-MG) and conditioned media from this primed BV2-MG can compromise the expression of EC-junction constituents when added to wild-type ECs. In an in vitro BBB model, KRAS-G12V-EC form a dysfunctional EC barrier that is further disrupted, leading to lower …

Optimizing Electrode Placement And Information Capacity For Local Field Potentials In Cortex, Jace A Willis, Christopher E Wright, Ruoqian Zhu, Yilan Ruan, Joshua Stallings, Amada M Abrego, Takfarinas Medani, Promit Moitra, Arjun Ramakrishnan, Charles E Schroeder, Anand A Joshi, Nitin Tandon, Richard M Leahy, John C Mosher, John P Seymour

Faculty, Staff and Student Publications

Recent neurosurgery advancements include improved stereotactic targeting and increased density and specificity of electrophysiological evaluation. This study introduces a subject-specific, in silico modeling tool for optimizing electrode placement and maximizing coverage with a variety of devices. The basis for optimization is the Shannon-Hartley information capacity of field potentials derived from dipolar sources. The approach integrates subject-specific MRI data with finite element modeling (FEM) used to simulate the sensitivity of subdural and intracortical devices. Sensitivity maps, or lead fields, from these models enable the comparison of different electrode placements, contact sizes, contact configurations, and substrate properties, which are often overlooked factors. …

Mechanized Tube Well Installation, Robert M. Stwalley Iii, Grace L. Baldwin Kan-Uge, Roger Tormoehlen

Purdue University Press Books

Mechanized Tube Well Installation provides detailed information on the design development of a mechanized means to install shallow tube wells using a hydraulic driver attached to a small vehicle. This book explores the creation of this technique through the merging of available components, selection of the components, testing of the assembly, and the driving of wells. It also provides comprehensive coverage of state-of-the-art engineering, technology, and best practices as they relate to driving water wells for human consumption, animal care, and irrigation. Mechanized Tube Well Installation is well-aligned with collegiate humanitarian aid, environmental and natural resources engineering, and agricultural equipment …

Applied Research For Corn Production In Indiana, 2022, Daniel Quinn

Purdue University Press Books

The 2022 edition of Applied Research for Corn Production in Indiana offers accessible, research-based tips for farmers who want to improve corn production practices by using applied field-research trials. Daniel Quinn and the Purdue University Corn Agronomy team reveal practical ways to boost yields, reduce costs, and improve sustainability on the farm. Their findings are derived from applied research trials across the state and relate to important topics such as planting practices, fertilizer use, crop nutrition, cover crops, and new technologies. Applied Research for Corn Production in Indiana distills complex research into clear insights and supplies corn producers with effective …

Advanced Design Topics For The Engineering Of Agricultural And Mechanical Equipment, Robert M. Stwalley Iii, Roger Tormoehlen

Purdue University Press Books

Off-road equipment designs contend with some unusual challenges and environmental conditions that are not seen by standard on-road vehicles. Advanced Design Topics for the Engineering of Agricultural and Mechanical Equipment offers design topic reviews related to areas that need special consideration within off-road applications. CAN-BUS systems, soil compaction, composite bearings, field welding practices, and weld strength in bending applications are examined, among other subjects. Providing comprehensive coverage of these matters with the current state-of-the-art technologies and best practices as they relate to equipment design for the agricultural, construction, forestry, and mining industries, this book is well-aligned with collegiate advanced agricultural …

Protocols In Root-Microbe Interactions, Anjali S. Iyer-Pascuzzi

Purdue University Press Books

Protocols in Root-Microbe Interactions describes laboratory protocols that have been developed and optimized for scientists working in root-microbe interactions, specifically for those wanting to quantify immune responses in plant roots. The experiments are focused on cellular to whole-root scale and include molecular biology, biochemistry, and histology techniques. Written in an easy-to-understand fashion that is suitable for both early career and experienced scientists, the protocols were optimized for tomato roots but can easily be adapted to roots of other plant species, or if needed, to leaves. The book includes information on quantifying pattern-triggered immune (PTI) responses in plant roots and covers …

Horse Evaluation: A Multibreed Text For Competitive Youth Equine Judges, Colleen M. Brady

Purdue University Press Books

Horse judging is one of the most popular activities in 4-H, FFA, and other youth-development organizations. Judging teaches youth how to both critically analyze animals based on a specific set of criteria and justify their decisions through oral reasoning. This book includes information on examining a wide variety of breeds—from quarter horses and Arabians to Saddlebreds, Drafts, and Miniatures—and covers a range of disciplines. Both halter and performance classes are explored, and the rules and regulations used to govern contests at the national level are provided. Example sets of reasons are supplied for most classes, as are lists of potential …

Clinical, Genetic, And Familial Features Of Pot1 Tumor Predisposition Syndrome, Courtney D Dinardo, Jennifer Croden, Hiam M Abdel-Salam, Tapan Kadia, Matteo Molica, Alexandre Bazinet, Prithviraj Bose, Abhishek Maiti, Fadi Haddad, Jan Burger, Hagop Kantarjian, William Wierda, Nitin Jain, Alessandra Ferrajoli

Faculty, Staff and Student Publications

Background: Protection of telomere 1 (POT1) tumor predisposition syndrome (POT1-TPD) is a hereditary leukemia syndrome that is identified in ∼5% of patients with chronic lymphocytic leukemia (CLL) and is characterized by a predisposition to other cancers, including gliomas, melanomas, and angiosarcomas. This study reports clinical and genetic characteristics of a large cohort of individuals with POT1-TPD.

Materials and methods: Individuals with pathogenic/likely pathogenic germline POT1 variants referred to the Hereditary Hematologic Malignancy Clinic at The University of Texas MD Anderson Cancer Center were included. Individuals with variants of uncertain significance were included if found to have telomeres >90th percentile of …

Control Arm Overperformance In Phase 3 Oncology Clinical Trials, Ansel P Nalin, Pavlos Msaouel, Adam J Grippin, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Avital M Miller, Noah S Meimoun, Ethan B Ludmir, Alexander D Sherry

Faculty, Staff and Student Publications

Background: In randomized clinical trials (RCTs), anticipating control arm outcomes is important for power calculations and enrollment goals. Unexpected overperformance of the control arm can underpower RCTs. The objective of this study was to estimate the prevalence of control arm overperformance in phase 3 oncology RCTs.

Methods: The authors conducted a meta-epidemiological study of two-arm, superiority-design, phase 3 oncology RCTs. They reviewed articles/publications and protocols for power calculations, justification, and outcomes. Control arm performance was measured as the ratio of observed control arm outcomes relative to pretrial estimates, and overperformance was defined as a 10% improvement.

Results: In total, 385 …

Antidepressant Use In Older Age Bipolar Disorder (Oabd): Results From The Gage-Bd International Consortium, Christina Rigas, Paola Lavin, P J Chen, Susana G Torres-Platas, Chien-Lin Su, Lisa T Eyler, Andrew T Olagunju, Antonio L Teixeira, Annemieke Dols, Martin Alda, Osvaldo P Almeida, Kursat Altinbas, Vicent Balanzá-Martínez, Izabela G Barbosa, Hilary P Blumberg, Farren B S Briggs, Cynthia V Calkin, Brent P Forester, Orestes V Forlenza, Tomas Hajek, Barthomeus C M Haarman, Esther Jimenez, Beny Lafer, Benoit Mulsant, Stephen O Oluwaniyi, Regan Patrick, Joaquim Radua, Kaylee Sarna, Sigfried Schouws, Christian Simhandl, Jair C Soares, Ashley N Sutherland, Shang-Ying Tsai, Eduard Vieta, Luca M Villa, Nicole Fiorelli, Paula Villela Nunes, Joy M Yala, Martha Sajatovic, Soham Rej, All Gage-Bd Investigators

Faculty, Staff and Student Publications

Background: Antidepressants are still commonly prescribed in bipolar disorders, despite ongoing controversy of the potential risk of inducing hypomania/mania. There is limited knowledge about the characteristics of antidepressant use in older age bipolar disorder (OABD; age ≥50) in the current literature.

Aim: To describe antidepressant use, sociodemographic and clinical correlates of a global sample of OABD individuals.

Methods: The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) consortium provided cross-sectional international data on OABD individuals (n = 746) and younger-age bipolar disorder (YABD, age < 50 years; n = 692) regarding antidepressant use. Multivariate logistic regression was employed to assess the association between AD use with demographic and clinical variables.

Results: Of 1252 participants, 33.1 % of OABD individuals and 38.1 % of YABD individuals …

Neuproio: A Dual-Action Solid Drug Nanoparticle Topical Formulation For Simultaneous Intraocular Pressure Reduction And Neuroprotection For Glaucoma, Lei Xu, Mu Li, Lin Qi, Tzu Chen Wang, Dong Liu, Vimalin Jeyalatha Mani, Hsin Yin Chuang, Qingbo Yang, Ruipu Mu, Samira Mahdi, Da Huang, Honglan Shi, Yang Hu, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Glaucoma is a leading cause of irreversible blindness, primarily due to elevated intraocular pressure (IOP) that damages the retina and optic nerve. Most topical glaucoma treatments focus solely on IOP-lowering without direct neuroprotection, as drug delivery to the posterior eye is challenging. Here, we developed NeuProIO, a dual-action solid drug nanoparticle (NP) eye drop for simultaneous IOP reduction and neuroprotection. Using flash nanoprecipitation in a multi-inlet vortex mixer, we fabricated the first NeuProIO solid drug NPs incorporating the repurposed neuroprotective agent maprotiline (MAP) and the IOP-lowering agent betaxolol (BX), forming MAP/BX NPs for synergistic glaucoma treatment. The NeuProIO improved stability …

Charting A New Era To Modernize United States Infant Formula Regulation, Douglas G Burrin, Amy B Hair, Sharon M Donovan

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Primary Membranoproliferative Glomerulonephritis: Natural History, Pathogenesis, And Treatment, Edward J. Filippone, John L. Farber

Division of Nephrology Faculty Papers

Primary membranoproliferative glomerulonephritis (MPGN) is an ultrarare disease characterized by immunofluorescence microscopy as either immune-complex mediated (IC-MPGN) or C3 glomerulopathy (C3), the latter subdivided by electron microscopy to C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both IC-MPGN and C3G typically have obvious C3 staining differentiating them from other causes of MPGN histology. Secondary causes must be excluded, including infections, autoimmune disease, and neoplasia. Clinical presentations are variable, including urinary sediment abnormalities, nephrotic syndrome, or a rapidly progressive course. The prognosis is unfavorable with about 50% reaching kidney failure by 10 years. Recurrence following transplantation is frequent, and allograft survival …

Erythropoiesis-Inosine Metabolic Axis Failure Underlying Retinal Neurodegeneration In Glaucoma: Novel Diagnoses And Therapies, Yuyu Chou, Wuping Liu, Yanxiu Li, Changhan Chen, Cheng Luo, Shiping Shen, Piaoyu Dai, Lemeng Feng, Wenhao Xiao, Yiyan Wang, Juncheng Wang, Linlin Wan, Zhiyu Yang, Tingting Xie, Yujin Zhang, Rodney E Kellems, Weitao Song, Xiaobo Xia, Yang Xia

Faculty, Staff and Student Publications

Glaucoma, long considered an ocular-limited, age-dependent and hypoxia-driven neurodegeneration, is here reframed as a systemic erythroid-inosine axis failure that originates in the bone marrow yet culminates in retinal ganglion cell (RGC) death. By mining UK Biobank datasets (n = 127,028) and validating our findings in an independent clinical cohort (n = 178), we reveal that glaucoma is preceded by dyserythropoiesis and a compensatory, AMPK-driven metabolic rewiring of mature erythrocytes that hypercatabolizes inosine to enhance oxygen unloading. This adaptation collapses when accelerated erythrocyte inosine metabolism drains systemic pools, starving high-energy demand hematopoietic progenitors, driving retinal microenvironment hypoxia and accelerating RGC loss. …

Rmzyme: Regulations Of Rna-Modifying Enzymes In Humans, Ruihan Luo, Haixia Xu, Qingbo Zhou, Shanli Ding, Min Qiang, Jianguo Wen, Pora Kim, Xiaojuan Yang, Yunshi Cai, Kunlin Xie, Jiang Zhu, Yungang Xu, Tian Lan, Xiaobo Zhou, Hong Wu

Faculty, Staff and Student Publications

RNA modifications represent a dynamic layer of gene expression regulation, RNA stability, and translation with profound implications for cellular function and disease. However, the critical regulation and functions of RNA-modifying proteins (RMPs) remain poorly understood. Here, we present a large-scale characterization of RMPs through 378 multiomics datasets encompassing genomics, bulk and single-cell transcriptomics, epitranscriptomics, proteomics, and posttranslational modifications (PTMs) across 63 human tissues. Our analysis of experimental perturbations of RMPs revealed dynamic differential modification peaks and expressed genes. We applied nonnegative matrix factorization to annotate RMP-mediated cell types in single-cell transcriptomes. Functional annotations in acute myeloid leukemia (AML) revealed RMPs …

Targeting Oxalate Production By Combining Enzyme Inhibition And Proteolysis Activation: A Novel Therapeutic Approach For Primary Hyperoxaluria Type 1, Fabio Arias, Sumati Rohilla, Yudibeth Sixto-López, Koral S E Richard, Sandeep Das, Sumit K Anand, Pilar Maria Luque-Navarro, Guillermo Bañuelos-Sanchez, Juan Luis Pacheco-García, Reethika Gade, M Peyton Mckinney, Dhananjay Kumar, Jemiah Maxie, W Rylan Corr, Nilesh Pandey, Harpreet Kaur, Jibin Ding, Lin Tan, Elisha Scott, Hyung Nam, Eyal Gottlieb, A Wayne Orr, Nirav Dhanesha, Arif Yurdagul, Angel L Pey, Francisco Franco-Montalbán, José A Gómez Vidal, Oren Rom, Mónica Díaz-Gavilán

Faculty, Staff and Student Publications

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder caused by hepatic oxalate overproduction due to alanine-glyoxylate aminotransferase (AGXT) deficiency. Therapeutic strategies targeting glycolate oxidase (GO) and lactate dehydrogenase A (LDHA), key enzymes in glyoxylate metabolism, have shown promise in reducing oxalate burden. However, recently approved siRNA therapies remain limited by high cost, unfavorable pharmacokinetics, and limited global accessibility. We report the development of compound 2, a dual GO/LDHA inhibitor (K i = 390 and 40 nM, respectively) that also promotes hydrophobic tag-mediated autophagic degradation of LDHA. Its efficacy was evaluated in Agxt –/– mice, both in primary …

Primary Tumor Size And Tumor-Vessel Interface Following Capecitabine And Temozolomide For Pancreatic Neuroendocrine Tumor, Jin Guo, Kever A Lewis, Laura Prakash, Priya Bhosale, Ajaykumar Morani, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma, Rebecca Snyder, Michael P Kim, Chandrikha Chandrasekharan, Arvind Dasari, James C Yao, Jeffrey E Lee, Jessica E Maxwell, Daniel M Halperin

Faculty, Staff and Student Publications

Capecitabine/temozolomide (CAPTEM) is an established regimen for patients with metastatic pancreatic neuroendocrine tumors (PanNET) that is being increasingly used for tumor volume reduction in patients with borderline anatomically resectable disease. We sought to understand the response of the primary tumor, defined as changes in the tumor–vascular interface (TVI). This is a retrospective, single-institution study of patients with locally advanced or metastatic PanNET treated with CAPTEM between 2010 and 2020. RECISTv1.1 measurements and TVI assessments of the primary tumor were performed on pre- and post-therapy images. Patients with locally advanced or metastatic PanNET at presentation (n = 47) were included. …

Tumor-Immune-Neural Circuit Disrupts Energy Homeostasis In Cancer Cachexia, Xiuhui Shi, Alex X Arreola, Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yang Cai, Yu Ren, Hao Yuan, Qun Chen, Xinjie Chen, Xinyu Yang, Yimei Meng, Jingyi Wang, Wenyi Luo, Michael C Rudolph, Rohan Varshney, Kar-Ming Fung, Chao Xu, Wei R Chen, Michael S Bronze, Lei Zheng, Yi-Ping Li, Courtney W Houchen, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

Cancer-induced cachexia and anorexia are debilitating complications across many cancers, yet effective treatments remain limited due to a poor understanding of the underlying mechanisms. Here, we identify an uncharacterized tumor-immune-neural circuit driving these syndromes, centered on growth and differentiation factor 15 (GDF15). Using genetically engineered mouse models, we find that loss of GDF15 protects against appetite loss, muscle wasting, and fat loss in pancreatic, lung, and skin cancers. Single-cell RNA sequencing reveals macrophages as a major source of GDF15, induced by tumor-derived colony-stimulating factor 1 (CSF1). GDF15 acts via the central nervous system to enhance β-adrenergic signaling in the tumor …

Weight Loss Patterns And Clinical Outcomes Of Glp1 Receptor Agonists In Breast Cancer Survivors, Jasmine S Sukumar, Akshara Singareeka Raghavendra, Sarah Pasyar, Roland L Bassett, Debu Tripathy, Carlos H Barcenas, Karen M Basen-Engquist, Banu K Arun

Faculty, Staff and Student Publications

Use of glucagon-like peptide-1 receptor agonists (GLP1-RA) for weight loss is increasing; implications in breast cancer (BC) survivors remain unclear.This retrospective cohort study evaluated treatment patterns, weight loss, and outcomes in BC survivors at an academic institution receiving GLP1-RA. We evaluated patients with non-metastatic (ductal carcinoma in situ (DCIS), stage 1-3) BC who received GLP1-RA (2005 - 2024). Linear regression models estimated associations between weight change and clinical factors. After excluding DCIS, propensity score matching (1:2) was used to match patients who received GLP1-RA with patients who did not, based on confounding covariates. Kaplan-Meier estimates and log-rank tests compared disease-free …

Albumin-Binding Domains In Therapeutic Protein Engineering: A Structural And Computational Perspective On Rational Design, Matthew Argyle, Dallin M. Chipman, Anna Claire Woolley, Bradley C. Bundy, Dennis Della Corte

Faculty Publications

Therapeutic proteins face a critical pharmacokinetic challenge: rapid clearance from circulation limits their clinical efficacy. Albumin-binding domains (ABDs) offer an elegant solution by enabling therapeutic proteins to “hitchhike” on serum albumin’s favorable 19-day half-life through FcRn-mediated recycling. Clinical validation through approved therapeutics like ozoralizumab demonstrates the success of this approach, with preclinical studies showing fusion to an ABD extended half-life to 18 days. This review provides an analysis of ABD-fusion protein design, integrating structural biology, computational prediction, and rational engineering principles. We catalog the major classes of albumin-binding modalities, including bacterial three-helix bundle domains, engineered peptides, antibody-derived binders, and alternative …

Temporal Dynamics Of Irrigation Characteristics In South Carolina, Selvalakshmi Selvaraj, Jose O. Payero, Dana B. Turner

Journal of South Carolina Water Resources

Irrigation plays a vital role in stabilizing crop production under climatic variability in the southeastern United States. However, limited long-term empirical evidence exists on how irrigation practices, water sources, and energy demands have evolved in South Carolina. The aim of this study was to examine temporal changes in irrigation characteristics in South Carolina. The analysis utilized two decades (2003–2023) of data from the United States Department of Agriculture – National Agricultural Statistics Service, Irrigation and Water Management Surveys. Results showed a 65% increase in the number of irrigated farms and 260% expansion in irrigated acreage over the twenty-year period. Groundwater …