Digital Commons Network^™

Outersphere Approach To Increasing The Persistance Of Oxygen-Sensitive Europium(Ii)-Containing Contrast Agents For Magnetic Resonance Imaging With Perfluorocarbon Nanoemulsions Toward Imaging Of Hypoxia, Jacob C Lutter, Andrea L Batchev, Caitlyn J Ortiz, Alexander G Sertage, Jonathan Romero, S A Amali S Subasinghe, Steen E Pedersen, Md Abul Hassan Samee, Robia G Pautler, Matthew J Allen

Faculty, Staff and Students Publications

Radiographic mapping of hypoxia is needed to study a wide range of diseases. Complexes of EuII are a promising class of molecules to fit this need, but they are generally limited by their rapid oxidation rates in vivo. Here, a perfluorocarbon-nanoemulsion perfused with N2, forms an interface with aqueous layers to hinder oxidation of a new perfluorocarbon-soluble complex of EuII. Conversion of the perfluorocarbon solution of EuII into nanoemulsions results in observable differences between reduced and oxidized forms by MRI both in vitro and in vivo. Oxidation in vivo occurrs over a period of ~30 min compared to <5 min for a comparable EuII-containing complex without nanoparticle interfaces. These results represent a critical step toward delivery of EuII-containing complexes in vivo for the study of hypoxia.

A Crispr/Cas9-Engineered Mouse Carrying A Conditional Knockout Allele For The Early Growth Response-1 Transcription Factor, Vineet K Maurya, Yan Ying, Denise G Lanza, Jason D Heaney, John P Lydon

Faculty, Staff and Students Publications

Early growth response 1 (EGR1) mediates transcriptional programs that are indispensable for cell division, differentiation and apoptosis in numerous physiologies and pathophysiologies. Whole-body EGR1 knockouts in mice (Egr1KO) have advanced our understanding of EGR1 function in an in vivo context. To extend the utility of the mouse to investigate EGR1 responses in a tissue- and/or cell-type-specific manner, we generated a mouse model in which exon 2 of the mouse Egr1 gene is floxed by CRISPR/Cas9 engineering. The floxed Egr1 alleles (Egr1f/f) are designed to enable spatiotemporal control of Cre-mediated EGR1 ablation in the …

Exploring The Role Of Vitamin D And The Gut Microbiome: A Cross-Sectional Study Of Individuals With Irritable Bowel Syndrome And Healthy Controls, Sarah W Matthews, Anna Plantinga, Robert Burr, Kevin C Cain, Tor Savidge, Kendra Kamp, Margaret M Heitkemper

Faculty, Staff and Students Publications

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with multifaceted pathophysiology. Prior studies have demonstrated higher rates of vitamin D deficiency in individuals with IBS compared to healthy controls (HC), as well as associations of vitamin D concentration with IBS symptoms. A systematic review of 10 mouse and 14 human studies reported a positive association between vitamin D (serum levels and supplementation) and beta diversity of gut microbiome in a variety of conditions. The present retrospective case-control study aimed to compare vitamin D (25(OH)D) plasma concentrations and gut microbiome composition in adult women with IBS (n=99) and …

Achieving Equity In Emergency Medicine Quality Measures Requires A Sex And Gender Lens, Ynhi T Thomas, Angela F Jarman, Nina G Faynshtayn, Greg B Buehler, Sara Andrabi, Alyson J Mcgregor

Faculty, Staff and Students Publications

BACKGROUND: Quality measures within Emergency Medicine (EM) were developed to standardize and improve care. Their development has been limited by lack of consideration of sex- and gender-based differences. Research has suggested that sex and gender can impact clinical care and treatment. Inclusion of sex and gender differences is needed to create EM quality measures that are equitable to all.

OBJECTIVE: The aim of the review is to provide a brief history of EM quality measures and the value of considering sex- and gender-based evidence in their development to ensure equity, using acute myocardial infarction (AMI) as an example.

DISCUSSION: Current …

The Effect Of Genetic Taste Status On Swallowing: A Literature Review, Theresa S. Lee, Angela M. Dietsch, Rana H. Damra, Rachel W. Mulheren

Department of Special Education and Communication Disorders: Faculty Publications

Purpose

Swallowing and taste share innervation pathways and are crucial to nutritive intake. Individuals vary in their perception of taste due to factors such as genetics; however, it is unclear to what extent genetic taste status influences swallowing physiology and function. The purpose of this review article is to provide background on genetic taste status, review the evidence on the association between genetic taste status and swallowing, and discuss research and clinical implications.

Method

A comprehensive literature review was conducted using search terms related to swallowing and genetic taste status. Studies were included if they investigated the main effect of …

Creativity In Energy Balance, Obesity And Feeding Behavior Research, Some Thoughts, Stephen J French, David B Allison

Children’s Nutrition Research Center Staff Publications

This review provides an overview of examples of especially creative work related to the fields of ingestive behavior, energetics (defined as the study of the acquisition, storage, and use of metabolizable energy by biological organisms and the causes and consequences of such acquisition, storage, and use), and nutrition, focusing on both individual works and discoveries, as well as bodies of works and in some cases the working styles of particular scientists. The paper then discusses some principles extracted from our observations as well as from the literature on creativity pointing out some factors that seem to make for more creative …

Towards A Model Of Biliary Atresia – Pilot Feasibility Study In Newborn Piglets, Thora Wesenberg Helt, Lene Buelund, Lise Borgwardt, Thomas Eriksen, Lars Johansen, Robin De Nijs, Soren Holm, Douglas G Burrin, Thomas Thymann, Vibeke Brix Christensen

Children’s Nutrition Research Center Staff Publications

Biliary atresia (BA) is a rare congenital liver disease with unknown etiology, and it is the most common indication for liver transplantation in children. As BA infants suffer from intestinal malabsorption and neurodevelopmental deficits, it is necessary to identify optimal medical and nutritional strategies using appropriate neonatal animal models. We aim to determine the feasibility of using newborn piglets with surgically induced cholestasis (bile duct ligation (BDL)) to mimic clinical features of BA. Six piglets were subjected to abdominal surgery on day 4 after birth. The bile ducts were ligated, and the piglet were followed for up to 12 days. …

Orchestration Of Mirna Patterns By Testosterone And Dietary Tomato Carotenoids During Early Prostate Carcinogenesis In Tramp Mice, Lei Wan, Jennifer M Thomas-Ahner, Dennis K Pearl, John W Erdman, Nancy E Moran, Steven K Clinton

Children’s Nutrition Research Center Staff Publications

Background: The integrative effects of prostate cancer risk factors, such as diet and endocrine status, on cancer-associated miRNA expression are poorly defined.

Objectives: This study aimed to define the influence of androgens and diet (tomato and lycopene) on prostatic miRNA expression during early carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model.

Methods: Wild type (WT) and TRAMP mice were fed control, tomato-containing, or lycopene-containing diets from 4 to 10 weeks of age. Mice underwent either sham (intact) or castration surgery at 8 wk, and half of the castrated mice received testosterone (2.5 mg/kg body weight/d) at 9 …

Co-Operative Roles Of Il-4rα And Il-13rα1 In The Progression Of Ovarian Carcinomas And The Survival Of Ovarian Carcinoma Patients, Won Ku Choi, Usama Khamis Hussein, Asmaa Gamal Ahmed, Junyue Zhang, Kyoung Min Kim, Ae Ri Ahn, Ho Sung Park, See-Hyoung Park, Dong Hyu Cho, Kyu Yun Jang

The Brown Foundation: Institute of Molecular Medicine

No abstract provided.

A Cre Driver Line For Genetic Targeting Of Kappa Opioid Receptor Expressing Cells, Franciely Paliarin, Chelsea Duplantis, Andrea F Jones, Jessica Cucinello-Ragland, Samhita Basavanhalli, Emily Blaze, Evan Doré, Anna Isabella Neel, Haiguo Sun, Rong Chen, Scott Edwards, Nicholas W Gilpin, Robert O Messing, Rajani Maiya

Faculty, Staff and Student Publications

Here we describe the generation and characterization of a Cre knock-in mouse line that harbors a Cre insertion in the 3′UTR of the κ opioid receptor gene (Oprk1) locus and provides genetic access to populations of κ opioid receptor (KOR)-expressing neurons throughout the brain. Using a combination of techniques including RNA in situ hybridization and immunohistochemistry, we report that Cre is expressed with high fidelity in KOR-expressing cells throughout the brain in this mouse line. We also provide evidence that Cre insertion does not alter basal KOR function. Baseline anxiety-like behaviors and nociceptive thresholds are unaltered in Oprk1-Cre …

Interferon Signaling Promotes Tolerance To Chromosomal Instability During Metastatic Evolution In Renal Cancer, Luigi Perelli, Federica Carbone, Li Zhang, Justin K Huang, Courtney Le, Hania Khan, Francesca Citron, Edoardo Del Poggetto, Tony Gutschner, Hideo Tomihara, Melinda Soeung, Rosalba Minelli, Sanjana Srinivasan, Michael Peoples, Truong Nguyen Anh Lam, Sebastian Lundgren, Ruohan Xia, Cihui Zhu, Alaa M T Mohamed, Jianhua Zhang, Kanishka Sircar, Alessandro Sgambato, Jianjun Gao, Eric Jonasch, Giulio F Draetta, Andrew Futreal, Ziad Bakouny, Eliezer M Van Allen, Toni Choueiri, Sabina Signoretti, Pavlos Msaouel, Kevin Litchfield, Samra Turajlic, Linghua Wang, Ying Bei Chen, Renzo G Di Natale, A Ari Hakimi, Virginia Giuliani, Timothy P Heffernan, Andrea Viale, Christopher A Bristow, Nizar M Tannir, Alessandro Carugo, Giannicola Genovese

Faculty, Staff and Student Publications

Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR-Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition of complex karyotypes in cancer cells. Cross-species analysis revealed that recurrent patterns of copy number variations, including 21q loss and dysregulation of the interferon pathway, are major drivers of metastatic potential. In vitro and in vivo genomic engineering, leveraging loss-of-function studies, along with a model of partial trisomy of chromosome 21q, demonstrated a dosage-dependent effect …

Examining Mechanisms For Voltage-Sensitive Calcium Channel-Mediated Secretion Events In Bone Cells, Perla C Reyes Fernandez, Christian S Wright, Mary C Farach-Carson, William R Thompson

Faculty, Staff and Student Publications

In addition to their well-described functions in cell excitability, voltage-sensitive calcium channels (VSCCs) serve a critical role in calcium (Ca2+)-mediated secretion of pleiotropic paracrine and endocrine factors, including those produced in bone. Influx of Ca2+ through VSCCs activates intracellular signaling pathways to modulate a variety of cellular processes that include cell proliferation, differentiation, and bone adaptation in response to mechanical stimuli. Less well understood is the role of VSCCs in the control of bone and calcium homeostasis mediated through secreted factors. In this review, we discuss the various functions of VSCCs in skeletal cells as regulators of Ca2+ dynamics and …

Ai In Drug Discovery And Its Clinical Relevance, Rizwan Qureshi, Muhammad Irfan, Taimoor Muzaffar Gondal, Sheheryar Khan, Jia Wu, Muhammad Usman Hadi, John Heymach, Xiuning Le, Hong Yan, Tanvir Alam

Faculty, Staff and Student Publications

The COVID-19 pandemic has emphasized the need for novel drug discovery process. However, the journey from conceptualizing a drug to its eventual implementation in clinical settings is a long, complex, and expensive process, with many potential points of failure. Over the past decade, a vast growth in medical information has coincided with advances in computational hardware (cloud computing, GPUs, and TPUs) and the rise of deep learning. Medical data generated from large molecular screening profiles, personal health or pathology records, and public health organizations could benefit from analysis by Artificial Intelligence (AI) approaches to speed up and prevent failures in …

Snakes And Ladders: A Potential Therapy Of Hepatocyte Growth Factor And Pigment Epithelium-Derived Factor In Pulmonary Hypertension, Joseph M Zambelas, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

No abstract provided.

Neoadjuvant Immunotherapy For Advanced, Resectable Non-Small Cell Lung Cancer: A Systematic Review And Meta-Analysis, Yajing Wu, Vivek Verma, Carl M Gay, Yujia Chen, Fei Liang, Qiang Lin, Jianing Wang, Wei Zhang, Zhouguang Hui, Min Zhao, Jun Wang, Joe Y Chang

Faculty, Staff and Student Publications

Background: Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes.

Methods: Eligibility was resectable stage I-III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For …

Three-Dimensional Printing Bioceramic Scaffolds Using Direct-Ink-Writing For Craniomaxillofacial Bone Regeneration, Vasudev Vivekanand Nayak, Blaire V Slavin, Edmara T P Bergamo, Andrea Torroni, Christopher M Runyan, Roberto L Flores, F Kurtis Kasper, Simon Young, Paulo G Coelho, Lukasz Witek

Faculty, Staff and Student Publications

Defects characterized as large osseous voids in bone, in certain circumstances, are difficult to treat, requiring extensive treatments which lead to an increased financial burden, pain, and prolonged hospital stays. Grafts exist to aid in bone tissue regeneration (BTR), among which ceramic-based grafts have become increasingly popular due to their biocompatibility and resorbability. BTR using bioceramic materials such as β-tricalcium phosphate has seen tremendous progress and has been extensively used in the fabrication of biomimetic scaffolds through the three-dimensional printing (3DP) workflow. 3DP has hence revolutionized BTR by offering unparalleled potential for the creation of complex, patient, and anatomic location-specific …

Stroke-Induced Respiratory Dysfunction Is Associated With Cognitive Decline, Anthony Patrizz, Ahmad El Hamamy, Michael Maniskas, Yashasvee Munshi, Louise Atadja, Hilda Ahnstedt, Matthew Howe, Fan Bu, Daniel K Mulkey, Louise D Mccullough, Jun Li

Faculty, Staff and Student Publications

BACKGROUND: Respiratory dysfunction is a common complication of stroke, with an incidence of over 60%. Despite the high prevalence of stroke-induced respiratory dysfunction, how disordered breathing influences recovery and cognitive outcomes after ischemic stroke is unknown. We hypothesized that stroke induces chronic respiratory dysfunction, breathing instability, and apnea in mice, which would contribute to higher mortality and greater poststroke cognitive deficits.

METHODS: Mice were subjected to a 60-minute transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion. Whole body plethysmography was performed on C57BL/6 young (2-3 months) and aged (20 months) male and female mice. Animals were …

Screening Hydrogels For Antifibrotic Properties By Implanting Cellularly Barcoded Alginates In Mice And A Non-Human Primate, Sudip Mukherjee, Boram Kim, Lauren Y Cheng, Michael David Doerfert, Jiaming Li, Andrea Hernandez, Lily Liang, Maria I Jarvis, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Trisha Ray, Tanguy Terlier, Cody Fell, Ping Song, Roberto N Miranda, Jose Oberholzer, David Yu Zhang, Omid Veiseh

Faculty, Staff and Student Publications

Screening implantable biomaterials for antifibrotic properties is constrained by the need for in vivo testing. Here we show that the throughput of in vivo screening can be increased by cellularly barcoding a chemically modified combinatorial library of hydrogel formulations. The method involves the implantation of a mixture of alginate formulations, each barcoded with human umbilical vein endothelial cells from different donors, and the association of the identity and performance of each formulation by genotyping single nucleotide polymorphisms of the cells via next-generation sequencing. We used the method to screen 20 alginate formulations in a single mouse and 100 alginate formulations …

Endoscopic Mucosal Resection: Tips And Tricks For Gastrointestinal Trainees, Tessa Herman, Bryant Megna, Kumar Pallav, Mohammad Bilal

Faculty, Staff and Student Publications

Endoscopic mucosal resection (EMR) is a minimally invasive, specialized endoscopic technique that is useful in resecting superficial gastrointestinal lesions that are unable to be removed by standard polypectomy. This is typically accomplished using a submucosal injection that lifts the lesion away from the muscularis propria to allow for safe resection of the polyp, either via piecemeal or en bloc resection. Over the years, several techniques exist to perform EMR including conventional EMR or hot EMR, cold EMR and underwater EMR. Despite its established advantages and safety over conventional techniques such as surgery, the adoption of endoscopic resection (and thus the …

Are Orthopedic Hand Surgeons Undercompensated For Time Spent In The Operating Room? A Study Of Relative Value Units, Trevor Simcox, Sakib Safi, Jacob Becker, Jason Kreinces, Adam Wilson

Faculty, Staff and Student Publications

Background: This study aims to investigate whether compensation is equitable among the most commonly performed orthopedic hand surgeries and when compared with general orthopedic procedures.

Methods: The National Surgical Quality Improvement Program database was queried for all orthopedic procedures, from 2016 to 2018, performed more than 150 times using Current Procedural Terminology (CPT) codes. Physician work relative value unit (wRVU) data were obtained from the 2020 US Centers for Medicare and Medicaid Services fee schedule. Linear regressions were used to determine whether there was an association among wRVU, operative time, and wRVU per hour (wRVU/h). Reimbursement for hand surgery CPT …

Satisfaction Of Older Patients With Emergency Department Care: Psychometric Properties And Construct Validity Of The Consumer Emergency Care Satisfaction Scale, Peter L T Hoonakker, Pascale Carayon, Roger L Brown, Rebecca Schwei, Rebecca K Green, Mackenzie Rabas, Ly Hoang, Kathryn L Wust, Rachel Rutkowski, Megan E Salwei, Hanna J Barton, Manish N Shah, Michael S Pulia, Brian W Patterson, Paula V W Dail, Sheryl Krause, Denise Buckley, Jennifer Hankwitz, Nicole E Werner

Faculty, Staff and Student Publications

BACKGROUND: Patient satisfaction is an important indicator of quality of care, but its measurement remains challenging. The Consumer Emergency Care Satisfaction Scale (CECSS) was developed to measure patient satisfaction in the emergency department (ED). Although this is a valid and reliable tool, several aspects of the CECSS need to be improved, including the definition, dimension, and scoring of scales.

PURPOSE: The purpose of this study was to examine the construct validity of the CECSS and make suggestions on how to improve the tool to measure overall satisfaction with ED care.

METHODS: We administered 2 surveys to older adults who presented …

Bystanders Or Not? Microglia And Lymphocytes In Aging And Stroke, Justin N Nguyen, Anjali Chauhan

Faculty, Staff and Student Publications

As the average age of the world population increases, more people will face debilitating aging-associated conditions, including dementia and stroke. Not only does the incidence of these conditions increase with age, but the recovery afterward is often worse in older patients. Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients. Aging causes profound changes in the immune system including the activation of microglia in the brain. Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation, white matter damage, and cognitive impairment in both older humans and …

Therapeutic Potential Of Salicylamide Derivatives For Combating Viral Infections, Jimin Xu, Yu Xue, Andrew A Bolinger, Jun Li, Mingxiang Zhou, Haiying Chen, Hongmin Li, Jia Zhou

Faculty, Staff and Student Publications

Since time immemorial human beings have constantly been fighting against viral infections. The ongoing and devastating coronavirus disease 2019 pandemic represents one of the most severe and most significant public health emergencies in human history, highlighting an urgent need to develop broad-spectrum antiviral agents. Salicylamide (2-hydroxybenzamide) derivatives, represented by niclosamide and nitazoxanide, inhibit the replication of a broad range of RNA and DNA viruses such as flavivirus, influenza A virus, and coronavirus. Moreover, nitazoxanide was effective in clinical trials against different viral infections including diarrhea caused by rotavirus and norovirus, uncomplicated influenza A and B, hepatitis B, and hepatitis C. …

Cisplatin Decreases Voluntary Wheel-Running Activity But Does Not Impair Food-Motivated Behavior In Mice, Kiersten S Scott, Brandon Chelette, Chinenye Chidomere, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Cisplatin is a chemotherapeutic agent that is still commonly used to treat solid tumors. However, it has several toxic side effects due in large part to the mitochondrial damage that it induces. As this mitochondrial damage is likely to result in a decrease in the amount of metabolic energy that is available for behavioral activities, it is not surprising that fatigue develops in cancer patients treated with cisplatin. The present preclinical study was initiated to determine whether the detrimental effects of cisplatin were more pronounced on physical effort requiring a lot of energy versus effort that not only requires less …

Addressing The Global Expertise Gap In Radiation Oncology: The Radiation Planning Assistant, Laurence Court, Ajay Aggarwal, Hester Burger, Carlos Cardenas, Christine Chung, Raphael Douglas, Monique Du Toit, David Jaffray, Anuja Jhingran, Michael Mejia, Raymond Mumme, Sikudhani Muya, Komeela Naidoo, Jerry Ndumbalo, Kelly Nealon, Tucker Netherton, Callistus Nguyen, Niki Olanrewaju, Jeannette Parkes, Willie Shaw, Christoph Trauernicht, Melody Xu, Jinzhong Yang, Lifei Zhang, Hannah Simonds, Beth M Beadle

Faculty, Staff and Student Publications

PURPOSE: Automation, including the use of artificial intelligence, has been identified as a possible opportunity to help reduce the gap in access and quality for radiotherapy and other aspects of cancer care. The Radiation Planning Assistant (RPA) project was conceived in 2015 (and funded in 2016) to use automated contouring and treatment planning algorithms to support the efforts of oncologists in low- and middle-income countries, allowing them to scale their efforts and treat more patients safely and efficiently (to increase access).

DESIGN: In this review, we discuss the development of the RPA, with a particular focus on clinical acceptability and …

Emerging Signaling Regulation Of Sinoatrial Node Dysfunction, Mingjie Zheng, Shannon Erhardt, Yuhan Cao, Jun Wang

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: The sinoatrial node (SAN), the natural pacemaker of the heart, is responsible for generating electrical impulses and initiating each heartbeat. Sinoatrial node dysfunction (SND) causes various arrhythmias such as sinus arrest, SAN block, and tachycardia/bradycardia syndrome. Unraveling the underlying mechanisms of SND is of paramount importance in the pursuit of developing effective therapeutic strategies for patients with SND. This review provides a concise summary of the most recent progress in the signaling regulation of SND.

RECENT FINDINGS: Recent studies indicate that SND can be caused by abnormal intercellular and intracellular signaling, various forms of heart failure (HF), …

Ceramide Compensation By Ceramide Synthases Preserves Retinal Function And Structure In A Retinal Dystrophy Mouse Model, Xinye Qian, Tanmay Srinivasan, Jessica He, Jiaxiong Lu, Yan Jin, Haiwei Gu, Rui Chen

Faculty, Staff and Students Publications

Increasing evidence has supported the role of ceramide as a mediator of photoreceptor dysfunction or cell death in ceramide accumulation and deficiency contexts. TLCD3B, a non-canonical ceramide synthase, was previously identified in addition to the six canonical ceramide synthases (CerSs), and the Tlcd3b-/- mouse model exhibited both retinal dysfunction and degeneration. As previous canonical CerS-deficient mouse models failed to display retinal degeneration, the mechanisms of how TLCD3B interacts with CerSs have not been investigated. Additionally, as the ceramide profile of each CerS is distinct, it is unclear whether the overall level or the homeostasis of different ceramide species plays a …

Nanoparticle Contrast-Enhanced Mri For Visualization Of Retroplacental Clear Space Disruption In A Mouse Model Of Placental Accreta Spectrum (Pas), Andrew A Badachhape, Prajwal Bhandari, Laxman Devkota, Mayank Srivastava, Eric A Tanifum, Verghese George, Karin A Fox, Chandrasekhar Yallampalli, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

Introduction:

Prior preclinical studies established the utility of liposomal nanoparticle blood-pool contrast agents in visualizing the retroplacental clear space (RPCS), a marker of normal placentation, while sparing fetuses from exposure because the agent does not cross the placental barrier. In this work, we characterized RPCS disruption in a mouse model of placenta accreta spectrum (PAS) using these agents.

Methods:

Contrast-enhanced MRI (CE-MRI) and computed tomography (CE-CT) using liposomal nanoparticles bearing gadolinium (liposomal-Gd) and iodine were performed in pregnant Gab3^−/− and wild type (WT) mice at day 16 of gestation. CE-MRI was performed on a 1T scanner using a 2D …

Advancing Asms With Lc-Ms/Ms For The Discovery Of Novel Pdcl2 Ligands From Dna-Encoded Chemical Library Selections, Qiuji Ye, Hassane Belabed, Yong Wang, Zhifeng Yu, Murugesan Palaniappan, Jian-Yuan Li, Stacey A Kalovidouris, Kevin R Mackenzie, Mingxing Teng, Damian W Young, Yoshitaka Fujihara, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: A safe, effective, and reversible nonhormonal male contraceptive drug is greatly needed for male contraception as well as for circumventing the side effects of female hormonal contraceptives. Phosducin-like 2 (PDCL2) is a testis-specific phosphoprotein in mice and humans. We recently found that male PDCL2 knockout mice are sterile due to globozoospermia caused by impaired sperm head formation, indicating that PDCL2 is a potential target for male contraception. Herein, our study for the first time developed a biophysical assay for PDCL2 allowing us to screen a series of small molecules, to study structure-activity relationships, and to discover two PDCL2 binders …

Targeting Aav Vectors To The Central Nervous System By Engineering Capsid-Receptor Interactions That Enable Crossing Of The Blood-Brain Barrier, Qin Huang, Albert T Chen, Ken Y Chan, Hikari Sorensen, Andrew J Barry, Bahar Azari, Qingxia Zheng, Thomas Beddow, Binhui Zhao, Isabelle G Tobey, Cynthia Moncada-Reid, Fatma-Elzahraa Eid, Christopher J Walkey, M Cecilia Ljungberg, William R Lagor, Jason D Heaney, Yujia A Chan, Benjamin E Deverman

Faculty, Staff and Students Publications

Viruses have evolved the ability to bind and enter cells through interactions with a wide variety of cell macromolecules. We engineered peptide-modified adeno-associated virus (AAV) capsids that transduce the brain through the introduction of de novo interactions with 2 proteins expressed on the mouse blood-brain barrier (BBB), LY6A or LY6C1. The in vivo tropisms of these capsids are predictable as they are dependent on the cell- and strain-specific expression of their target protein. This approach generated hundreds of capsids with dramatically enhanced central nervous system (CNS) tropisms within a single round of screening in vitro and secondary validation in vivo …