Digital Commons Network^™

Novel Genetic And Phenotypic Expansion In Gosr2-Related Progressive Myoclonus Epilepsy, Lea Hentrich, Mered Parnes, Timothy Edward Lotze, Rohini Coorg, Tom J De Koning, Kha M Nguyen, Calvin K Yip, Heinz Jungbluth, Anne Koy, Hormos Salimi Dafsari

Faculty, Staff and Students Publications

Biallelic variants in the Golgi SNAP receptor complex member 2 gene (GOSR2) have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we report two novel patients from unrelated families with a GOSR2-related disorder and novel genetic and clinical findings. The first patient, a male compound heterozygous for the GOSR2 splice site variant c.336+1G>A and the novel c.364G>A,p.Glu122Lys missense variant showed global developmental delay and seizures at the age of 2 years, followed by myoclonus at the age …

A Rare Cause Of Diarrhea: Intestinal Spirochetosis In An Hiv-Positive Patient., Lacey Falgout, Shilpa Kailas, Supraja Sridhar, Nisha Loganantharaj

School of Medicine Faculty Publications

Intestinal spirochetosis (IS) is a rare gastrointestinal infection with vague presenting symptoms. Diagnosis is confirmed histopathologically. Risk factors include homosexuality and HIV. Antibiotic treatment with metronidazole usually leads to resolution of symptoms. We present the case of a 56-year-old HIV-positive man with chronic, watery diarrhea who was diagnosed with IS. This case highlights the importance of considering IS in the differential in HIV-positive patients with nonspecific gastrointestinal symptoms after more common etiologies have been ruled out.

A Retrospective Review Of 30-Day Hospital Readmission Risk After Open Heart Surgery In Patients With Atrial Fibrillation, Varun Ashutosh Rao, Genaro Deleon, Aish Thamba, Mindy Flanagan, Kathleen Nickel, Douglas Gray Md

Medical Student Research

Introduction

Readmission rates after open heart surgery (OHS) remain an important clinical issue. The causes are varied, with identifying risk factors potentially providing valuable information to reduce healthcare costs and the rate of post-operative complications. This study aimed to characterize the reasons for 30-day hospital readmission rates of patients after open heart surgery.

Methods

All patients over 18 years of age undergoing OHS at a community hospital from January 2020 through December 2020 were identified. Demographic data, medical history, operative reports, post-operative complications, and telehealth interventions were obtained through chart review. Descriptive statistics and readmission rates were calculated, along with …

Comparative Genomics Analysis Of Three Conserved Plasmid Families In The Western Hemisphere Soft Tick-Borne Relapsing Fever Borreliae Provides Insight Into Variation In Genome Structure And Antigenic Variation Systems, Alexander R Kneubehl, Job E Lopez

Faculty, Staff and Students Publications

Borrelia spirochetes, causative agents of Lyme disease and relapsing fever (RF), have uniquely complex genomes, consisting of a linear chromosome and both circular and linear plasmids. The plasmids harbor genes important for the vector-host life cycle of these tick-borne bacteria. The role of plasmids from Lyme disease causing spirochetes is more refined compared to RF Borrelia because of limited plasmid-resolved genome assemblies for the latter. We recently addressed this limitation and found that three linear plasmid families (F6, F27, and F28) were syntenic across all the RF Borrelia species that we examined. Given this conservation, we further investigated the three …

Boosting Glycolysis To Combat Fragile Bone In Type 1 Diabetes, Zixue Jin, Brendan Lee

Faculty, Staff and Students Publications

Individuals with type 1 diabetes (T1D) have an increased risk of osteoporosis and fracture. In this issue of Cell Chemical Biology, Ji et al.1 show that impaired glucose metabolism in the bone-forming osteoblast drives diabetic osteoporosis in Akita mice, a mouse model of T1D.

Epichaperome Inhibition Targets Tp53-Mutant Aml And Aml Stem/Progenitor Cells, Bing Z Carter, Po Yee Mak, Muharrem Muftuoglu, Wenjing Tao, Baozhen Ke, Jingqi Pei, Andrea D Bedoy, Lauren B Ostermann, Yuki Nishida, Sevinj Isgandarova, Mary Sobieski, Nghi Nguyen, Reid T Powell, Margarita Martinez-Moczygemba, Clifford Stephan, Mahesh Basyal, Naveen Pemmaraju, Steffen Boettcher, Benjamin L Ebert, Elizabeth J Shpall, Barbara Wallner, Robert A Morgan, Georgios I Karras, Ute M Moll, Michael Andreeff

Faculty, Staff and Student Publications

TP 53-mutant acute myeloid leukemia (AML) remains the ultimate therapeutic challenge. Epichaperomes, formed in malignant cells, consist of heat shock protein 90 (HSP90) and associated proteins that support the maturation, activity, and stability of oncogenic kinases and transcription factors including mutant p53. High-throughput drug screening identified HSP90 inhibitors as top hits in isogenic TP53-wild-type (WT) and -mutant AML cells. We detected epichaperomes in AML cells and stem/progenitor cells with TP53 mutations but not in healthy bone marrow (BM) cells. Hence, we investigated the therapeutic potential of specifically targeting epichaperomes with PU-H71 in TP53-mutant AML based on its preferred binding to …

Evaluation Of Acceptability, Functionality, And Validity Of A Passive Image-Based Dietary Intake Assessment Method In Adults And Children Of Ghanaian And Kenyan Origin Living In London, Uk, Modou L Jobarteh, Megan A Mccrory, Benny Lo, Konstantinos K Triantafyllidis, Jianing Qiu, Jennifer P Griffin, Edward Sazonov, Mingui Sun, Wenyan Jia, Tom Baranowski, Alex K Anderson, Kathryn Maitland, Gary Frost

Children’s Nutrition Research Center Staff Publications

Background: Accurate estimation of dietary intake is challenging. However, whilst some progress has been made in high-income countries, low- and middle-income countries (LMICs) remain behind, contributing to critical nutritional data gaps. This study aimed to validate an objective, passive image-based dietary intake assessment method against weighed food records in London, UK, for onward deployment to LMICs.

Methods: Wearable camera devices were used to capture food intake on eating occasions in 18 adults and 17 children of Ghanaian and Kenyan origin living in London. Participants were provided pre-weighed meals of Ghanaian and Kenyan cuisine and camera devices to automatically capture images …

Nlrp3 Selectively Drives Il-1Β Secretion By Pseudomonas Aeruginosa Infected Neutrophils And Regulates Corneal Disease Severity, Martin S Minns, Karl Liboro, Tatiane S Lima, Serena Abbondante, Brandon A Miller, Michaela E Marshall, Jolynn Tran Chau, Alicia Roistacher, Arne Rietsch, George R Dubyak, Eric Pearlman

Faculty, Staff and Student Publications

Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1β secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1β secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1β secretion. While IL-1β release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity …

Chronic Cough Relief By Allosteric Modulation Of P2x3 Without Taste Disturbance, Chang-Run Guo, Zhong-Zhe Zhang, Xing Zhou, Meng-Yang Sun, Tian-Tian Li, Yun-Tao Lei, Yu-Hao Gao, Qing-Quan Li, Chen-Xi Yue, Yu Gao, Yi-Yu Lin, Cui-Yun Hao, Chang-Zhu Li, Peng Cao, Michael X Zhu, Ming-Qiang Rong, Wen-Hui Wang, Ye Yu

Faculty, Staff and Student Publications

P2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs …

Kcnq2/3 Gain-Of-Function Variants And Cell Excitability: Differential Effects In Ca1 Versus L2/3 Pyramidal Neurons, Nissi Varghese, Bruno Moscoso, Ana Chavez, Kristen Springer, Erika Ortiz, Heun Soh, Sabato Santaniello, Atul Maheshwari, Anastasios V Tzingounis

Faculty, Staff and Students Publications

Gain-of-function (GOF) pathogenic variants in the potassium channels KCNQ2 and KCNQ3 lead to hyperexcitability disorders such as epilepsy and autism spectrum disorders. However, the underlying cellular mechanisms of how these variants impair forebrain function are unclear. Here, we show that the R201C variant in KCNQ2 has opposite effects on the excitability of two types of mouse pyramidal neurons of either sex, causing hyperexcitability in layer 2/3 (L2/3) pyramidal neurons and hypoexcitability in CA1 pyramidal neurons. Similarly, the homologous R231C variant in KCNQ3 leads to hyperexcitability in L2/3 pyramidal neurons and hypoexcitability in CA1 pyramidal neurons. However, the effects of KCNQ3 …

Critical Functions Of Extracellular Matrix In Brain Metastasis Seeding, Arseniy E Yuzhalin, Dihua Yu

Faculty, Staff and Student Publications

Human brain is characterized by extremely sparse extracellular matrix (ECM). Despite its low abundance, the significance of brain ECM in both physiological and pathological conditions should not be underestimated. Brain metastasis is a serious complication of cancer, and recent findings highlighted the contribution of ECM in brain metastasis development. In this review, we provide a comprehensive outlook on how ECM proteins promote brain metastasis seeding. In particular, we discuss (1) disruption of the blood-brain barrier in brain metastasis; (2) role of ECM in modulating brain metastasis dormancy; (3) regulation of brain metastasis seeding by ECM-activated integrin signaling; (4) functions of …

Epigenetic Induction Of Smooth Muscle Cell Phenotypic Alterations In Aortic Aneurysms And Dissections, Abhijit Chakraborty, Yanming Li, Chen Zhang, Yang Li, Kimberly R Rebello, Shengyu Li, Samantha Xu, Hernan G Vasquez, Lin Zhang, Wei Luo, Guangyu Wang, Kaifu Chen, Joseph S Coselli, Scott A Lemaire, Ying H Shen

Faculty, Staff and Students Publications

BACKGROUND: Smooth muscle cell (SMC) phenotypic switching has been increasingly detected in aortic aneurysm and dissection (AAD) tissues. However, the diverse SMC phenotypes in AAD tissues and the mechanisms driving SMC phenotypic alterations remain to be identified.

METHODS: We examined the transcriptomic and epigenomic dynamics of aortic SMC phenotypic changes in mice with angiotensin II-induced AAD by using single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin. SMC phenotypic alteration in aortas from patients with ascending thoracic AAD was examined by using single-cell RNA sequencing analysis.

RESULTS: Single-cell RNA sequencing analysis revealed that aortic stress induced the transition of …

Mir-146a Inhibits Ovarian Tumor Growth In Vivo Via Targeting Immunosuppressive Neutrophils And Enhancing Cd8+ T Cell Infiltration, Rui Chen, Elaina Coleborn, Chintan Bhavsar, Yue Wang, Louisa Alim, Andrew N Wilkinson, Michelle A Tran, Gowri Irgam, Sharat Atluri, Kiefer Wong, Jae-Jun Shim, Siddharth Adityan, Ju-Seog Lee, Willem W Overwijk, Raymond Steptoe, Da Yang, Sherry Y Wu

Faculty, Staff and Student Publications

Immunotherapies have emerged as promising strategies for cancer treatment. However, existing immunotherapies have poor activity in high-grade serous ovarian cancer (HGSC) due to the immunosuppressive tumor microenvironment and the associated low tumoral CD8+ T cell (CTL) infiltration. Through multiple lines of evidence, including integrative analyses of human HGSC tumors, we have identified miR-146a as a master regulator of CTL infiltration in HGSC. Tumoral miR-146a expression is positively correlated with anti-cancer immune signatures in human HGSC tumors, and delivery of miR-146a to tumors resulted in significant reduction in tumor growth in both ID8-p53−/− and IG10 murine HGSC models. Increasing miR-146a expression …

Abcc1 And Glutathione Metabolism Limit The Efficacy Of Bcl-2 Inhibitors In Acute Myeloid Leukemia, Jessica Ebner, Johannes Schmoellerl, Martin Piontek, Gabriele Manhart, Selina Troester, Bing Z Carter, Heidi Neubauer, Richard Moriggl, Gergely Szakács, Johannes Zuber, Thomas Köcher, Michael Andreeff, Wolfgang R Sperr, Peter Valent, Florian Grebien

Faculty, Staff and Student Publications

The BCL-2 inhibitor Venetoclax is a promising agent for the treatment of acute myeloid leukemia (AML). However, many patients are refractory to Venetoclax, and resistance develops quickly. ATP-binding cassette (ABC) transporters mediate chemotherapy resistance but their role in modulating the activity of targeted small-molecule inhibitors is unclear. Using CRISPR/Cas9 screening, we find that loss of ABCC1 strongly increases the sensitivity of AML cells to Venetoclax. Genetic and pharmacologic ABCC1 inactivation potentiates the anti-leukemic effects of BCL-2 inhibitors and efficiently re-sensitizes Venetoclax-resistant leukemia cells. Conversely, ABCC1 overexpression induces resistance to BCL-2 inhibitors by reducing intracellular drug levels, and high ABCC1 levels …

Narrative Review Of The Role Of Technology In Pediatric Diabetes: From Testing Blood Glucose To Subcutaneous Automated Therapy And Hope For Cure, Michael Yafi, Avni Shah, Katherine Velez

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Type 1 diabetes, the most common cause of diabetes in pediatrics, is defined by the hyperglycemia that results from the permanent autoimmune damage to the pancreas. The Diabetes Control and Complications Trial (DCCT) demonstrated that strict glycemic control targeting lower HbA1c goals can both delay the onset and progression of its complications that include diabetic neuropathy, nephropathy, retinopathy, and increased cardiovascular events. Our primary objective is to review the literature available regarding the technology applied for the treatment of diabetes, not only aiding patients' quality of life but addressing its effects on hypoglycemia and reduced risk of …

Aspergillus Flavus And Fusarium Verticillioides And Their Main Mycotoxins: Global Distribution And Scenarios Of Interactions In Maize, Xiangrong Chen, Mohamed F Abdallah, Sofie Landschoot, Kris Audenaert, Sarah De Saeger, Xiangfeng Chen, Andreja Rajkovic

Faculty, Staff and Student Publications

Maize is frequently contaminated with multiple mycotoxins, especially those produced by Aspergillus flavus and Fusarium verticillioides. As mycotoxin contamination is a critical factor that destabilizes global food safety, the current review provides an updated overview of the (co-)occurrence of A. flavus and F. verticillioides and (co-)contamination of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) in maize. Furthermore, it summarizes their interactions in maize. The gathered data predict the (co-)occurrence and virulence of A. flavus and F. verticillioides would increase worldwide, especially in European cold climate countries. Studies on the interaction of both fungi regarding their growth mainly showed antagonistic …

Neuroimmune Support Of Neuronal Regeneration And Neuroplasticity Following Cerebral Ischemia In Juvenile Mice, Ricaurte A Marquez-Ortiz, Vesna Tesic, Daniel R Hernandez, Bilkis Akhter, Nibedita Aich, Porter M Boudreaux, Garrett A Clemons, Celeste Yin-Chieh Wu, Hung Wen Lin, Krista M Rodgers

Faculty, Staff and Student Publications

Ischemic damage to the brain and loss of neurons contribute to functional disabilities in many stroke survivors. Recovery of neuroplasticity is critical to restoration of function and improved quality of life. Stroke and neurological deficits occur in both adults and children, and yet it is well documented that the developing brain has remarkable plasticity which promotes increased post-ischemic functional recovery compared with adults. However, the mechanisms underlying post-stroke recovery in the young brain have not been fully explored. We observed opposing responses to experimental cerebral ischemia in juvenile and adult mice, with substantial neural regeneration and enhanced neuroplasticity detected in …

Classification Of Missense Variants In The N-Methyl-D-Aspartate Receptor Grin Gene Family As Gain- Or Loss-Of-Function, Scott J Myers, Hongjie Yuan, Riley E Perszyk, Jing Zhang, Sukhan Kim, Kelsey A Nocilla, James P Allen, Jennifer M Bain, Johannes R Lemke, Dennis Lal, Timothy A Benke, Stephen F Traynelis

Faculty, Staff and Student Publications

Advances in sequencing technology have generated a large amount of genetic data from patients with neurological conditions. These data have provided diagnosis of many rare diseases, including a number of pathogenic de novo missense variants in GRIN genes encoding N-methyl-d-aspartate receptors (NMDARs). To understand the ramifications for neurons and brain circuits affected by rare patient variants, functional analysis of the variant receptor is necessary in model systems. For NMDARs, this functional analysis needs to assess multiple properties in order to understand how variants could impact receptor function in neurons. One can then use these data to determine whether the …

Characterization Of An Mtbp Hypomorphic Allele In A Diethylnitrosamine-Induced Liver Carcinogenesis Model, Atul Ranjan, Elizabeth A. Thoenen, Atsushi Kaida, Stephanie Wood, Terry Van Dyke, Tomoo Iwakuma

Manuscripts, Articles, Book Chapters and Other Papers

MTBP is implicated in cell cycle progression, DNA replication, and cancer metastasis. However, the function of MTBP remains enigmatic and is dependent on cellular contexts and its cellular localization. To understand the in vivo physiological role of MTBP, it is important to generate Mtbp knockout mice. However, complete deletion of the Mtbp gene in mice results in early embryonic lethality, while its heterozygous deletion shows modest biological phenotypes, including enhanced cancer metastasis. To overcome this and better characterize the in vivo physiological function of MTBP, we, for the first time, generated mice that carry an Mtbp hypomorphic allele (MtbpH …

A Review Of The Role Of Tendon Stem Cells In Tendon-Bone Regeneration, Junjie Chen, Chuanfeng Jiang, Lu Yin, Yingqi Liu, Yue He, Sen Li, Huarui Shen

Faculty, Staff and Student Publications

Tendon-bone injuries are a prevalent health concern associated with sports and other physically demanding activities. These injuries have a limited innate healing ability, often leading to the formation of scar tissue rather than the regeneration of healthy tendon tissue. This scar tissue results from excessive fibrosis during the early healing process and often leads to reduced tendon function and an increased risk of reinjury. Traditionally, surgical reconstruction has been the primary treatment for tendon-bone injuries. However, restoring the natural structure and mechanical properties of tendons after surgical reconstruction presents a considerable challenge. Recently, the potential of stem cell therapy has …

Ciliochoroidal Melanoma Masquerading As A Conjunctival Nevus, Samantha Pastore, Konica Singla, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.

Hematopoietic Stem And Progenitor Cells Confer Cross-Protective Trained Immunity In Mouse Models, Bailee N Kain, Brandon T Tran, Pamela N Luna, Ruoqiong Cao, Duy T Le, Marcus A Florez, Laure Maneix, Jack D Toups, Daniel E Morales-Mantilla, Scott Koh, Hyojeong Han, Roman Jaksik, Yun Huang, Andre Catic, Chad A Shaw, Katherine Y King

Duncan NRI Faculty and Staff Publications

Recent studies suggest that infection reprograms hematopoietic stem and progenitor cells (HSPCs) to enhance innate immune responses upon secondary infectious challenge, a process called “trained immunity.” However, the specificity and cell types responsible for this response remain poorly defined. We established a model of trained immunity in mice in response to Mycobacterium avium infection. scRNA-seq analysis revealed that HSPCs activate interferon gamma-response genes heterogeneously upon primary challenge, while rare cell populations expand. Macrophages derived from trained HSPCs demonstrated enhanced bacterial killing and metabolism, and a single dose of recombinant interferon gamma exposure was sufficient to induce similar training. Mice transplanted …

Structure, Function, And Molecular Landscapes Of The Aging Retina, Jeffrey D Zhu, Sharma Pooja Tarachand, Qudrat Abdulwahab, Melanie A Samuel

Faculty, Staff and Students Publications

Because the central nervous system is largely nonrenewing, neurons and their synapses must be maintained over the lifetime of an individual to ensure circuit function. Age is a dominant risk factor for neural diseases, and declines in nervous system function are a common feature of aging even in the absence of disease. These alterations extend to the visual system and, in particular, to the retina. The retina is a site of clinically relevant age-related alterations but has also proven to be a uniquely approachable system for discovering principles that govern neural aging because it is well mapped, contains diverse neuron …

Decoding Depression Severity From Intracranial Neural Activity, Jiayang Xiao, Nicole R Provenza, Joseph Asfouri, John Myers, Raissa K Mathura, Brian Metzger, Joshua A Adkinson, Anusha B Allawala, Victoria Pirtle, Denise Oswalt, Ben Shofty, Meghan E Robinson, Sanjay J Mathew, Wayne K Goodman, Nader Pouratian, Paul R Schrater, Ankit B Patel, Andreas S Tolias, Kelly R Bijanki, Xaq Pitkow, Sameer A Sheth

Faculty, Staff and Students Publications

BACKGROUND: Disorders of mood and cognition are prevalent, disabling, and notoriously difficult to treat. Fueling this challenge in treatment is a significant gap in our understanding of their neurophysiological basis.

METHODS: We recorded high-density neural activity from intracranial electrodes implanted in depression-relevant prefrontal cortical regions in 3 human subjects with severe depression. Neural recordings were labeled with depression severity scores across a wide dynamic range using an adaptive assessment that allowed sampling with a temporal frequency greater than that possible with typical rating scales. We modeled these data using regularized regression techniques with region selection to decode depression severity from …

Neurocognitive Outcomes In Adult Survivors Of Neuroblastoma: A Report From The Childhood Cancer Survivor Study, Caroline Hesko, Wei Liu, Deo K Srivastava, Tara M Brinkman, Lisa Diller, Todd M Gibson, Kevin C Oeffinger, Wendy M Leisenring, Rebecca Howell, Gregory T Armstrong, Kevin R Krull, Tara O Henderson

Faculty, Staff and Student Publications

Background: Despite survival improvements, there is a paucity of data on neurocognitive outcomes in neuroblastoma survivors. This study addresses this literature gap.

Methods: Neurocognitive impairments in survivors were compared to sibling controls from the Childhood Cancer Survivor Study (CCSS) using the CCSS Neurocognitive Questionnaire. Impaired emotional regulation, organization, task efficiency, and memory defined as scores ≥90th percentile of sibling norms. Modified Poisson regression models evaluated associations with treatment exposures, era of diagnosis, and chronic conditions. Analyses were stratified by age at diagnosis (≤1 and >1 year) as proxy for lower versus higher risk disease.

Results: Survivors (N = 837; median …

N-Terminal Α-Amino Sumoylation Of Cofilin-1 Is Critical For Its Regulation Of Actin Depolymerization, Weiji Weng, Xiaokun Gu, Yang Yang, Qiao Zhang, Qi Deng, Jie Zhou, Jinke Cheng, Michael X Zhu, Junfeng Feng, Ou Huang, Yong Li

Faculty, Staff and Student Publications

Small ubiquitin-like modifier (SUMO) typically conjugates to target proteins through isopeptide linkage to the ε-amino group of lysine residues. This posttranslational modification (PTM) plays pivotal roles in modulating protein function. Cofilins are key regulators of actin cytoskeleton dynamics and are well-known to undergo several different PTMs. Here, we show that cofilin-1 is conjugated by SUMO1 both in vitro and in vivo. Using mass spectrometry and biochemical and genetic approaches, we identify the N-terminal α-amino group as the SUMO-conjugation site of cofilin-1. Common to conventional SUMOylation is that the N-α-SUMOylation of cofilin-1 is also mediated by SUMO activating (E1), conjugating (E2), …

Speg Interactions That Regulate The Stability Of Excitation-Contraction Coupling Protein Complexes In Triads And Dyads, Chang Seok Lee, Sung Yun Jung, Rachel Sue Zhen Yee, Nadia H Agha, Jin Hong, Ting Chang, Lyle W Babcock, Jorie D Fleischman, Benjamin Clayton, Amy D Hanna, Christopher S Ward, Denise Lanza, Ayrea E Hurley, Pumin Zhang, Xander H T Wehrens, William R Lagor, George G Rodney, Susan L Hamilton

Faculty, Staff and Students Publications

Here we show that striated muscle preferentially expressed protein kinase α (Spegα) maintains cardiac function in hearts with Spegβ deficiency. Speg is required for stability of excitation-contraction coupling (ECC) complexes and interacts with esterase D (Esd), Cardiomyopathy-Associated Protein 5 (Cmya5), and Fibronectin Type III and SPRY Domain Containing 2 (Fsd2) in cardiac and skeletal muscle. Mice with a sequence encoding a V5/HA tag inserted into the first exon of the Speg gene (HA-Speg mice) display a >90% decrease in Spegβ but Spegα is expressed at ~50% of normal levels. Mice deficient in both Spegα and Speg β (Speg KO mice) …

Anti-Inflammatory And Antioxidant Effects Of Sea Urchin Spine Extract, Dina Magdy El Gamal

The Undergraduate Research Journal

Diadema savignyi spine extract in an experimental setup using L929 cell line in vitro. The cell metabolic activity of L929 cells is tested through an MTT assay. The sea urchin spine extract is applied to the cells in two concentrations: 100 μg/ml (136% viability) and 200 μg/ml (95% viability). The bioactive components of the sea urchin spine are identified via GC-MS, and the antioxidant and anti-inflammatory activities are evaluated using catalase assay (CAT), glutathione (GSH), and nitric oxide (NO) tests. Results show that the GC-MS identified bioactive components including the anti-inflammatory and anti-irritant bisabolol oxide and the pro-inflammatory oleic acid. …

Identification Of Sentinel Lymph Nodes In Esophageal Cancer Patients Using Contrast-Enhanced Eus With Peritumoral Injections, Ji-Bin Liu, Priscilla Machado, John R. Eisenbrey, Sriharsha Gummadi, Flemming Forsberg, Corinne E. Wessner, Anand Raman Kumar, Austin Chiang, Anthony Infantolino, Alexander Schlachterman, Thomas Kowalski, Robert Coben, David Loren

Department of Medicine Faculty Papers

OBJECTIVES: The objective of this pilot study was to compare the performance of contrast-enhanced EUS (CE-EUS)-guided fine-needle aspiration (FNA) with EUS-FNA for lymph node (LN) staging in esophageal cancer.

METHODS: Thirty-seven subjects with esophageal cancer undergoing EUS staging were enrolled, and 30 completed this institutional review board-approved study. A Prosound F75 US system (Hitachi Medical Systems, Tokyo, Japan) with harmonic contrast imaging software and GF-UCT180 curvilinear endoscope (Olympus, Tokyo, Japan) was utilized. All LNs identified by standard EUS were first noted. Sonazoid (dose: 1 mL; GE Healthcare, Oslo, Norway) was administered peritumorally, and all enhanced LNs were recorded. Fine-needle aspiration …

Examining Pi3k-Signaling-Dependent Regulation Of Lens Organelle Free Zone Formation Via Immunolocalization And Immunoblotting In Chick Embryos, Rifah Gheyas, A. Sue Menko

Computational Medicine Center Faculty Papers

The elimination of lens organelles during development, required for mature lens function, is an autophagy-dependent mechanism induced through suppression of PI3K signaling. Here, we present a protocol for investigating the signaling pathways responsible for induction of the formation of this lens organelle free zone. We describe steps for preparation of lens organ culture and use of signaling pathway inhibitors. We then detail procedures for analyzing their impact using both confocal microscopy imaging of immunolabeled lens cryosections and immunoblot approaches. For complete details on the use and execution of this protocol, please refer to Gheyas et al. (2022).