Digital Commons Network^™

Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We …

Leveraging Human Microbiomes For Disease Prediction And Treatment, Henok Ayalew Tegegne, Tor C Savidge

Faculty, Staff and Students Publications

The human microbiome consists of diverse microorganisms that inhabit various body sites. As these microbes are increasingly recognized as key determinants of health, there is significant interest in leveraging individual microbiome profiles for early disease detection, prevention, and drug efficacy prediction. However, the complexity of microbiome data, coupled with conflicting study outcomes, has hindered its integration into clinical practice. This challenge is partially due to demographic and technological biases that impede the development of reliable disease classifiers. Here, we examine recent advances in 16S rRNA and shotgun-metagenomics sequencing, along with bioinformatics tools designed to enhance microbiome data integration for precision …

Caveolin-Mediated Endocytosis: Bacterial Pathogen Exploitation And Host-Pathogen Interaction, Dibyasri Barman, Rishi Drolia

Biological Sciences Faculty Publications

Within mammalian cells, diverse endocytic mechanisms, including phagocytosis, pinocytosis, and receptor-mediated endocytosis, serve as gateways exploited by many bacterial pathogens and toxins. Among these, caveolae-mediated endocytosis is characterized by lipid-rich caveolae and dimeric caveolin proteins. Caveolae are specialized microdomains on cell surfaces that impact cell signaling. Caveolin proteins facilitate the creation of caveolae and have three members in vertebrates: caveolin-1, caveolin-2, and caveolin-3. Many bacterial pathogens hijack caveolin machinery to invade host cells. For example, the Gram-positive facultative model intracellular bacterial pathogen Listeria monocytogenes exploits caveolin-mediated endocytosis for efficient cellular entry, translocation across the intestinal barrier, and cell–cell spread. Caveolin …

Zika Virus Modulates Arthropod Histone Methylation For Its Survival In Mosquito Cells, Telvin Harrell

Biological Sciences Faculty Publications

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes mild febrile illness in adults and severe neurological complications and microcephaly in newborns. Studies have reported that ZIKV modulates methylation of human and viral RNA critical for its replication in vertebrate cells. In this study, we show that ZIKV modulates mosquito S-adenosyl methionine (SAMe)-synthase, an enzyme involved in the production of SAMe (methyl donor), and histone methylation for its survival in mosquito cells. Reverse transcription quantitative PCR followed by immunoblotting analysis showed increased amounts of SAMe synthase at both RNA and protein levels, respectively, in C6/36 mosquito cells infected with …

Mapping Of Rorγt+ Dendritic Cells In Human Tissues Establishes Their Preferential Niche In Adult Lymph Nodes, Silvia Lonardi, Shitong Wu, Alina Ulezko Antonova, Yizhou A Liu, Marina Cella, Marco Colonna, William Vermi, Et Al.

2020-Current year OA Pubs

BACKGROUND: The retinoic-acid-receptor-related orphan receptor gamma t (RORγt) isoform is required for the development of lymphoid organs, T-helper 17 cells (Th17), and innate lymphoid cells (ILC3s). Recent data in mouse and human have revealed non-T, non-ILC3 cell populations with antigen presenting features that express RORγt. This study maps the presence of RORγt cells with dendritic cell (DC) features in human adult and fetal lymphoid tissues.

METHODS: By combining multicolor flow cytometry, RNAseq of peripheral blood cells, analysis of lymph node scRNAseq datasets, and microscopic analysis on human tissue sections and single-cell suspensions, this study maps the presence of RORγt cells …

New Genetic Tools To Define The Pathophysiology Of Inborn Errors Of Cobalamin Metabolism Impacting Mammalian Development, Tiffany Chern, Xuefei Tong, William G Bauer, David J Quispe-Parra, Xia Gao, Kamryn N Gerner-Mauro, Ross A Poché

Children’s Nutrition Research Center Staff Publications

The congenital, autosomal recessive disorder combined methylmalonic acidemia and homocystinuria - cblC type, is the most common inborn error of cobalamin (vitamin B12) metabolism. In its early onset form, cblC profoundly impacts fetal development of the central nervous system, hematopoietic system, and other tissues. Previously, mutations in the MMACHC gene, which encodes a protein required for the intracellular trafficking and enzymatic processing of free cobalamin into active coenzyme forms, were found to cause cblC. These coenzymes are required in two metabolic pathways which produce either succinyl-CoA in the mitochondria or methionine in the cytosol. However, due to a lack of …

A Reflection-Spectroscopy Measured Skin Carotenoid Score Strongly Correlates With Plasma Concentrations Of All Major Dietary Carotenoid Species Except For Lycopene, Qiang Wu, Cheryl Webb Cherry, Stephanie Jilcott Pitts, Melissa N Laska, Neal Craft, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoids can be measured non-invasively using spectroscopy methods to provide a biomarker of total dietary carotenoid and carotenoid-rich fruit and vegetable intake. However, the degree to which skin carotenoid biomarkers reflect intakes of specific carotenoids must be determined for specific devices. Previously, findings were mixed regarding the correlation between reflection spectroscopy (RS)-assessed skin carotenoids and individual plasma carotenoid concentrations. The current study expands on prior analyses to examine the cross-sectional associations between adult RS-assessed skin carotenoids and individual carotenoid species intakes and plasma concentrations, controlling for potential covariates. We hypothesized that RS-assessed skin carotenoid scores would strongly correlate with …

Regulatory B Cells, The Key Regulator To Induce Immune Tolerance In Organ Transplantation, Jinfeng Liao, Yixin Yang, Jisong Li, Zheng Liu, Siyuan Song, Yu Zeng, Yi Wang

Children’s Nutrition Research Center Staff Publications

In solid organ transplantation, especially renal transplantation, for the induction of immune tolerance, accumulating evidence has revealed that Regulatory B cells (Breg) play a crucial role in stimulating immune tolerance, alleviating immune responses, and improving graft survival. We describe the heterogeneous nature of Bregs, focusing on their defining surface markers and regulatory functions. Meanwhile, the major cytokine secretion function and the correlation between Breg and Treg or other immune checkpoints to balance the immune responses are addressed. Furthermore, we summarized the intrinsic and extrinsic pathways or costimulatory stimuli for the differentiation from naïve B cells. More importantly, we summarized the …

Molecular Evidence Of Brucella Abortus Circulating In Cattle, Goats, And Humans In Central Equatoria State, South Sudan, Emmanuel Philip Lasuba Lita, Ernatus M. Mkupas, Erneo B. Och, Gerald Misinzo, Henriette Van Heerden, Robab Katani, Jacques Godfroid, Coletha Mathew

All Rsif Scholars' Publications

Brucellosis is a neglected zoonotic disease in most developing countries, including South Sudan. Precise identification of Brucella species is crucial for addressing public health and epidemiological concerns associated with brucellosis. The study aimed to identify Brucella species using real-time polymerase chain reaction (qPCR) from seropositive samples that were acquired from an earlier investigation. A total of 143 genomic DNA samples were extracted from brucellosis Rose Bengal plate test (RBPT) seropositive samples from humans (n=7), cattle (n=103) and goats (n=33). The samples were collected from Terekeka and Juba counties, Central Equatoria State (CES), South Sudan. The qPCR targeting the Brucella-specific IS711 …

Multisociety Guidance For Infection Prevention And Control In Nursing Homes, Lona Mody, Sonali D. Advani, Muhammad Salman Ashraf, Allison H. Bartlett, Suzanne F. Bradley, Deborah P. Burdsall, Jennifer A. Hanrahan, Susan S. Huang, Robert L.P. Jump, Lindsay Nicolle, Mary-Claire Roghmann, Patricia Stone, Rekha K. Murthy

Department of Medicine Faculty Publications

This multisociety guidance was endorsed by SHEA, APIC, IDSA, PALTmed, and AGS. It provides recommendations for infection prevention and control (IPC) in the context of the complexity of nursing home care in the United States: increased medical acuity of residents, the spread of multidrug-resistant organisms, and the threat of emerging pathogens. Recommendations and implementation suggestions address IPC leadership, staffing, and resources, healthcare personnel and residents‘ adherence to precautions and effective hand hygiene, outbreak preparedness, training, occupational health, cleaning and disinfection in the care environment, and the involvement of IPC in the facility. The guidance also addresses the challenges of maintaining …

Confidence In Elections Among U.S. Local Officials: Effects Of Social Trust, Partisanship And Political Ambition, Rebecca Sager, Eric Plutzer, Gary Adler, Jonathan S. Coley, Damon Maryl

Sociology Faculty Works

The U.S. public’s confidence in elections is intensively studied in the last decade but little is known about election confidence among locally elected officials, whose roles and community status may influence public opinion. Using a nationally representative survey of local election officials, we compare election confidence among local elected officials with that of the general public. Local elected officials are more likely to trust both local and national elections. We theorize factors that affect local officials’ trust in elections, including partisan context, state leadership election denial levels, and political ambition. We show how social trust, partisan identity, and ambition significantly …

Mechanisms And Environmental Factors Shaping The Ecosystem Of Brain Macrophages, Silvia Penati, Simone Brioschi, Zhangying Cai, Claudia Z Han, Marco Colonna

The Brown Foundation: Institute of Molecular Medicine

Brain macrophages encompass two major populations: microglia in the parenchyma and border-associated macrophages (BAMs) in the extra-parenchymal compartments. These cells play crucial roles in maintaining brain homeostasis and immune surveillance. Microglia and BAMs are phenotypically and epigenetically distinct and exhibit highly specialized functions tailored to their environmental niches. Intriguingly, recent studies have shown that both microglia and BAMs originate from the same myeloid progenitor during yolk sac hematopoiesis, but their developmental fates diverge within the brain. Several works have partially unveiled the mechanisms orchestrating the development of microglia and BAMs in both mice and humans; however, many questions remain unanswered. …

Intestinal Oxygen Utilisation And Cellular Adaptation During Intestinal Ischaemia-Reperfusion Injury, Paraschos Archontakis-Barakakis, Theodoros Mavridis, David-Dimitris Chlorogiannis, Georgios Barakakis, Eleni Laou, Daniel I Sessler, George Gkiokas, Athanasios Chalkias

Faculty, Staff and Student Publications

The gastrointestinal tract can be deranged by ailments including sepsis, trauma and haemorrhage. Ischaemic injury provokes a common constellation of microscopic and macroscopic changes that, together with the paradoxical exacerbation of cellular dysfunction and death following restoration of blood flow, are collectively known as ischaemia-reperfusion injury (IRI). Although much of the gastrointestinal tract is normally hypoxemic, intestinal IRI results when there is inadequate oxygen availability due to poor supply (pathological hypoxia) or abnormal tissue oxygen use and metabolism (dysoxia). Intestinal oxygen uptake usually remains constant over a wide range of blood flows and pressures, with cellular function being substantively compromised …

Reproducibility And Repeatability Of 18f-(2s, 4r)-4-Fluoroglutamine Pet Imaging In Preclinical Oncology Models, Gregory D Ayers, Allison S Cohen, Seong-Woo Bae, Xiaoxia Wen, Alyssa Pollard, Shilpa Sharma, Trey Claus, Adria Payne, Ling Geng, Ping Zhao, Mohammed Noor Tantawy, Seth T Gammon, H Charles Manning

Faculty, Staff and Student Publications

Introduction: Measurement of repeatability and reproducibility (R&R) is necessary to realize the full potential of positron emission tomography (PET). Several studies have evaluated the reproducibility of PET using 18F-FDG, the most common PET tracer used in oncology, but similar studies using other PET tracers are scarce. Even fewer assess agreement and R&R with statistical methods designed explicitly for the task. 18F-(2S, 4R)-4-fluoro-glutamine (18F-Gln) is a PET tracer designed for imaging glutamine uptake and metabolism. This study illustrates high reproducibility and repeatability with 18F-Gln for in vivo research.

Methods: Twenty mice bearing colorectal cancer cell line xenografts were injected with ~9 …

Selective Inhibition Of Canonical Stat3 Signaling Suppresses K-Ras Mutant Lung Tumorigenesis And Reinvigorates Anti-Tumor Immunity, Michael J Clowers, Zahraa Rahal, Sung-Nam Cho, Avantika Krishna, Bo Yuan, Leticia G Hamana Zorrilla, T Kris Eckols, Moses M Kasembeli, Samuel Liu, Stephen Peng, Marco Ramos-Castaneda, Annamarie L Thompson, Carlos Ignacio Rodriguez Reyna, Katherine E Larsen, Maria T Grimaldo, Shanshan Deng, Nastaran Karimi, Cody Chou, Walter V Velasco, Melody Zarghooni, Sayan Alekseev, Luisa M Solis Soto, Edwin J Ostrin, Humam Kadara, Suhendan Ekmekcioglu, David J Tweardy, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

Introduction: K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. One of the lynchpins of chronic inflammation in KM-LUAD is signal transducer and activator of transcription 3 (STAT3).

Methods: Here, we tested the anti-tumor and early immunotherapeutic efficacy of TTI-101, a selective small-molecule inhibitor of canonical STAT3 signaling, in a K-rasG12D mutant lung cancer mouse model (CC-LR).

Results: Treatment of CC-LR mice with TTI-101 resulted in reduced …

Inhibition Of Nitric Oxide Synthase Transforms Carotid Occlusion-Mediated Benign Oligemia Into De Novo Large Cerebral Infarction, Ha Kim, Jinyong Chung, Jeong Wook Kang, Dawid Schellingerhout, Soo Ji Lee, Hee Jeong Jang, Inyeong Park, Taesu Kim, Dong-Seok Gwak, Ji Sung Lee, Sung-Ha Hong, Kang-Hoon Je, Hee-Joon Bae, Joohon Sung, Eng H Lo, James Faber, Cenk Ayata, Dong-Eog Kim

Faculty, Staff and Student Publications

No abstract provided.

Psychometric Evaluation Of A Novel Measure Of Trauma-Related Cannabis Use To Cope, Sage E. Hawn, Terrell A. Hicks, Christopher Latourrette, Anita Thomas, Daniela Chaname, Sarah Ehlke, Abigail Powers Lott

Psychology Faculty Publications

Background: Posttraumatic stress disorder (PTSD) and cannabis use disorder (CUD) are commonly comorbid and are associated with many negative public health outcomes. One plausible explanation for this comorbidity comes from a self-medication framework, which suggests people use cannabis to cope with PTSD symptoms. Despite theoretical and empirical evidence for PTSD-related cannabis use to cope, no measure of this construct exists.

Objective: We sought to address this gap by developing and validating a novel measure of PTSD-specific cannabis self-medication, which we have termed the Trauma-Related Cannabis Use to Cope (TRCU) questionnaire.

Method: The psychometric properties of the TRCU and how it …

Neutrophils Unveiled In Chronic Lymphocytic Leukemia, Sheighlah Mcmanus, Priyanka Khare, Maria Teresa S Bertilaccio

Faculty, Staff and Student Publications

This review explores neutrophils' roles in chronic lymphocytic leukemia (CLL), highlighting their functions within the immune system. While neutrophils are known for fighting infections, their altered behavior in CLL significantly impacts disease progression. This review notes the reduced phagocytic abilities of neutrophils and the increased formation of neutrophil extracellular traps (NETs) in patients with CLL. It also examines the effects of CLL treatments, including chemotherapy, immunotherapy and targeted therapies, on neutrophils' count and function, stressing the need for improved strategies to manage therapy-induced immune dysfunction. This review also provides detailed information about the interactions between neutrophils and other immune elements …

Nutritional Management Of The Child With Chronic Kidney Disease And On Dialysis., Vanessa Shaw, Caroline Anderson, An Desloovere, Larry A. Greenbaum, Lyndsay Harshman, Christina L. Nelms, Pearl Pugh, Nonnie Polderman, José Renken-Terhaerdt, Evelien Snauwaert, Stella Stabouli, Jetta Tuokkola, Johan Vande Walle, Bradley A. Warady, Fabio Paglialonga, Rukshana Shroff

Manuscripts, Articles, Book Chapters and Other Papers

While it is widely accepted that the nutritional management of the infant with chronic kidney disease (CKD) is paramount to achieve normal growth and development, nutritional management is also of importance beyond 1 year of age, particularly in toddlers, to support the delayed infantile stage of growth that may extend to 2-3 years of age. Puberty is also a vulnerable period when nutritional needs are higher to support the expected growth spurt. Inadequate nutritional intake throughout childhood can result in failure to achieve full adult height potential, and there is an increased risk for abnormal neurodevelopment. Conversely, the rising prevalence …

Histopathologic Progression And Metastatic Relapse Outcomes In Small Cell Neuroendocrine Carcinomas Of The Urinary Tract, Mohammad Jad Moussa, Georges C Tabet, Arlene O Siefker-Radtke, Lianchun Xiao, Nathaniel R Wilson, Jianjun Gao, Christopher J Logothetis, Petros Grivas, Byron Lee, Amishi Y Shah, Pavlos Msaouel, Roger Li, Leticia Campos Clemente, Jianping Zhao, Nizar M Tannir, Ashish M Kamat, Donna E Hansel, Charles C Guo, Matthew T Campbell, Omar Alhalabi

Faculty, Staff and Student Publications

Introduction: Small cell neuroendocrine carcinoma of the urinary tract (SCNEC-URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery.

Materials and methods: We identified a definitive-surgery cohort (n = 224) from an institutional database of patients with cT1-T4NxM0 SCNEC-URO treated in 1985-2021. Histopathologic review was conducted by independent pathologists. Relapse event was the time-to-event outcome, and relapse probabilities were estimated using a competing risk method with cumulative incidence functions (CIFs). Fine-Gray distribution models assessed covariate associations.

Results: Most patients (161, 71.9%) received neoadjuvant chemotherapy (neoCTX). Ninety two (41%) …

Relationship Between Trpm4 Rs8104571 Genotype, Circulating Trpm4 And Sur1, And Clinical Outcome Following Traumatic Brain Injury, Joseph D Krocker, Madeline E Cotton, Janet R Ashley, Jacob B Schriner, Baron K Osborn, Yao-Wei Willa Wang, Charles S Cox, Charles E Wade

Faculty, Staff and Student Publications

The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients. Trauma patients with moderate to severe TBI were included in this retrospective study. rs8104571 genotyping and admission …

Mutation Of Conserved Mhc Class I Cytoplasmic Tyrosine Affects Cd8+ T Cell Priming, Effector Function, And Memory Response, Yimo Sun, Yitao Tang, Priscilla Ortiz, Barbara Nassif Rausseo, Barbara Pazdrak, Lama Elzohary, Arjun Katailiha, Amjad Talukder, Cassian Yee, Richard Eric Davis, Gregory Lizée

Faculty, Staff and Student Publications

The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2Kb had reduced capacity to generate Kb-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due at least in part to defects in endolysosomal trafficking of H-2Kb and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of MHC-I containing Y320F …

New Anhydramnios After 22 Weeks And Pulmonary Hypoplasia, Aaron W Roberts, Margaret Clement, Suzanne Marie Lopez, Rita Swinford, Percy Pacora Portella, Edgar Hernandez-Andrade, Matthew Rysavy, Anthony Johnson

Faculty, Staff and Student Publications

Introduction: Anhydramnios due to renal failure prior to 22 weeks of gestational age (WGA) is associated with lethal pulmonary hypoplasia but after 22 WGA outcomes are less clear. We evaluated whether these fetuses, with new anhydramnios after 22 WGA, incur significant risk of severe neonatal pulmonary morbidity.

Methods: This retrospective study of singleton pregnancies diagnosed with new-onset renal anhydramnios after 22 WGA following verifiable normal AFI on ultrasound before 22 WGA from 2021 to 2023. Cases with bilateral renal agenesis, premature rupture of membranes, and nonrenal malformations were excluded.

Results: During the study period 53,698 s trimester ultrasound examinations were …

Safety Of Indocyanine Green Microdosing For Clinical Imaging Of Csf Ventricular Dynamics And Extracranial Outflow, Miriam Zamorano, Banghe Zhu, Ahmed T Massoud, Jonathan Hendricks, H Alex Choi, Pedram Peesh, Brandon A Miller, Xinhai Robert Zhang, Manish N Shah, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Background and purpose: Intravenous administration of indocyanine green (ICG) has been approved in brain surgeries for decades, yet concerns about neurotoxicity prevent its direct administration into the cerebrospinal fluid (CSF). Armed with prior animal studies demonstrating the feasibility of using ICG microdosing into the CSF, we sought to evaluate its nonclinical safety profile and obtain surrogate measures in adults prior to its use in human neonates.

Methods: Evaluation of ICG toxicity was conducted in mixed primary CNS cell cultures and in an extended safety study of juvenile rat pups deploying intraventricular injections of saline (as control) or ICG. Analysis of …

Correlation Of Pancreatic Laminin Alpha 5 Expression With Clinical Outcomes In Total Pancreatectomy With Islet Autotransplantation, Jayachandra Kuncha, Carly M Darden, Yang Liu, Michael Lawrence, J Sebastian Danobeitia, Bashoo Naziruddin

Faculty, Staff and Student Publications

This study examines extracellular matrix (ECM) protein (ECM) expression in chronic pancreatitis (CP) patients and its correlation with graft function after total pancreatectomy with islet autologous transplantation (TPIAT). Pancreatic sections from 29 CP patients undergoing TPIAT were analyzed for ECM including pan-laminin, laminin alpha 5 (LAMA5), collagen IV, and Perlecan by immunohistochemistry and scored by the percentage positive staining area within the whole tissue area. Graft function was monitored by blood glucose and C-peptide levels. Laminin alpha 5 levels in blood plasma were greater in CP. Laminin alpha 5 expression was significantly higher in all CP patient etiological categories including …

Stim1 And Lipid Interactions At Er-Pm Contact Sites, Yuepeng Ke, Ritchel Gannaban, Junchen Liu, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated calcium (Ca2+) entry (SOCE) represents a major route of Ca2+ permeation across the plasma membrane (PM) in non-excitable cells, which plays an indispensable role in maintaining intracellular Ca2+ homeostasis. This process is orchestrated through the dynamic coupling between the endoplasmic reticulum (ER)-localized Ca2+ sensor stromal interaction molecule 1 (STIM1) and the PM-resident ORAI1 channel. Upon depletion of ER Ca2+ stores, STIM1 undergoes conformational rearrangements and oligomerization, leading to translocation of STIM1-containing ER membrane towards the PM. This movement is facilitated by the physical interaction between positively charged cytosolic domains within STIM1 and negatively charged phospholipids embedded in the PM, …

Limitations Of The Radiotheranostic Concept In Neuroendocrine Tumors Due To Lineage-Dependent Somatostatin Receptor Expression On Hematopoietic Stem And Progenitor Cells, Nghia Nguyen, Yu Min, Jennifer Rivière, Mark Van Der Garde, Sukhen Ghosh, Laura M Bartos, Matthias Brendel, Florian Bassermann, Ali Azhdarinia, Wolfgang A Weber, Katharina S Götze, Susanne Kossatz

Faculty, Staff and Student Publications

Rationale: Radiopharmaceutical therapy (RPT) has become an effective treatment option for neuroendocrine tumors (NETs) and castration-resistant prostate cancer and is in clinical development for many indications. One of the major advantages of theranostic RPT is that the distribution of radiopharmaceuticals in the human body can be imaged, and radiation doses to the patient's organs can be calculated. However, accurate dosimetry may be fundamentally limited by microscopic heterogeneity of radiopharmaceutical distribution.

Methods: We developed fluorescent analogs of somatostatin-receptor-subtype 2 (SSTR2) targeting Lutetium-177 labeled radiopharmaceuticals that are clinically used in patients with NETs and studied their uptake by hematopoietic stem and progenitor …

Peripheral Administration Of Blood From Tau Transgenic Animals Exacerbates Brain Tau-Associated Pathology, Laura Vegas-Gomez, Matias Pizarro, Jesus Garcia-Martin, Maria Angeles Arredondo-Alcala, Bianca Bustamante, Carolina Gonzalez-Silva, Soledad Matus, Rodrigo Diaz-Espinoza, Antonia Gutierrez, Rodrigo Morales, Claudia Duran-Aniotz, Ines Moreno-Gonzalez

Faculty, Staff and Student Publications

The accumulation of amyloid plaques and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD). While amyloid-beta propagation through prion-like mechanisms has been extensively studied in both central and peripheral pathways, the potential spreading of tau aggregates in the periphery remains largely unexplored. Emerging evidence suggests that hyperphosphorylated tau (ptau) aggregates may propagate beyond the central nervous system, as they have been detected in peripheral tissues and biological fluids from humans and mouse models of tauopathies. However, whether peripheral ptau aggregates or other factors associated to its accumulation contribute to brain pathology remains unclear. In this study, we investigate the …

Nrg Oncology White Paper On The Relative Biological Effectiveness In Proton Therapy, Harald Paganetti, Charles B Simone, Walter R Bosch, Daphne Haas-Kogan, David G Kirsch, Heng Li, Xiaoying Liang, Wei Liu, Anita Mahajan, Michael D Story, Paige A Taylor, Henning Willers, Ying Xiao, Jeffrey C Buchsbaum

Faculty, Staff and Student Publications

This position paper, led by the NRG Oncology Particle Therapy Work Group, focuses on the concept of relative biologic effect (RBE) in clinical proton therapy (PT), with the goal of providing recommendations for the next-generation clinical trials with PT on the best practice of investigating and using RBE, which could deviate from the current standard proton RBE value of 1.1 relative to photons. In part 1, current clinical utilization and practice are reviewed, giving the context and history of RBE. Evidence for variation in RBE is presented along with the concept of linear energy transfer (LET). The intertwined nature of …

Optimization Of Proximity Labeling In Endothelial Cells: Overcoming Endogenous Biotin Interference And Cost Barriers, Ying Jiang, Kuizhi Qu, Mengjun Dai, Yan-Ning Rui, Zhen Xu

Faculty, Staff and Student Publications

Proximity labeling has become a powerful technique for mapping protein-protein interactions under physiologically relevant conditions, with TurboID offering high enzymatic activity and rapid labeling. However, its application in endothelial systems has been limited, partly due to the presence of endogenous biotin in specialized media, which reduces labeling specificity. Here, we optimized TurboID-mediated proximity labeling in brain microvascular endothelial cells by addressing two key challenges: endogenous biotin interference and cost-effective depletion. We discovered that endothelial cell medium contains substantial biotin levels, which saturate TurboID labeling and obscure the effects of exogenous biotin. Using High Capacity NeutrAvidin