Digital Commons Network^™

Tp53-Pten-Nf1 Depletion In Human Brain Organoids Produces A Glioma Phenotype In Vitro, Sanjay K Singh, Yan Wang, Ahmed Habib, Mamindla Priyadarshini, Chowdari V Kodavali, Apeng Chen, Wencai Ma, Jing Wang, N U Farrukh Hameed, Baoli Hu, Gregory N Fuller, Scott M Kulich, Nduka Amankulor, Rivka R Colen, Lincoln A Edwards, Pascal O Zinn

Faculty, Staff and Student Publications

Glioblastoma (GBM) is fatal and the study of therapeutic resistance, disease progression, and drug discovery in GBM or glioma stem cells is often hindered by limited resources. This limitation slows down progress in both drug discovery and patient survival. Here we present a genetically engineered human cerebral organoid model with a cancer-like phenotype that could provide a basis for GBM-like models. Specifically, we engineered a doxycycline-inducible vector encoding shRNAs enabling depletion of the TP53, PTEN, and NF1 tumor suppressors in human cerebral organoids. Designated as inducible short hairpin-TP53-PTEN-NF1 (ish-TPN), doxycycline treatment resulted in human cancer-like cerebral organoids that effaced the …

Association Of Cyclooxygenase-2 Expression With Endoplasmic Reticulum Stress And Autophagy In Triple-Negative Breast Cancer, Haechan Lee, Sungwook Jung, Gyungyub Gong, Bora Lim, Hee Jin Lee

Faculty, Staff and Student Publications

Cyclooxygenase-2 plays a role in oncogenesis and its overexpression is associated with triple-negative breast cancer. However, the mechanisms whereby cyclooxygenase-2 contribute to breast cancer are complex and not well understood. Cyclooxygenase-2 overexpression causes hypoxia, oxidative stress, and endoplasmic reticulum stress. The aim of this study is to investigate the correlations among cyclooxygenase-2 expression, endoplasmic reticulum stress-associated molecules, and autophagy-associated molecules in triple-negative breast cancer. Surgical specimens from two cohorts of triple-negative breast cancer patients without neoadjuvant systemic therapy were analyzed: cohorts 1 and 2 consisted of 218 cases from 2004 to 2006 and 221 cases from 2007 to 2009, respectively. …

Circadian Rhythms Of Risk Factors And Management In Atherosclerotic And Hypertensive Vascular Disease: Modern Chronobiological Perspectives Of An Ancient Disease, Yong-Jian Geng, Michael H Smolensky, Oliver Sum-Ping, Ramon Hermida, Richard J Castriotta

Faculty, Staff and Student Publications

Atherosclerosis, a chronic inflammatory disease of the arteries that appears to have been as prevalent in ancient as in modern civilizations, is predisposing to life-threatening and life-ending cardiac and vascular complications, such as myocardial and cerebral infarctions. The pathogenesis of atherosclerosis involves intima plaque buildup caused by vascular endothelial dysfunction, cholesterol deposition, smooth muscle proliferation, inflammatory cell infiltration and connective tissue accumulation. Hypertension is an independent and controllable risk factor for atherosclerotic cardiovascular disease (CVD). Conversely, atherosclerosis hardens the arterial wall and raises arterial blood pressure. Many CVD patients experience both atherosclerosis and hypertension and are prescribed medications to concurrently …

Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation And Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose, Takashi Maruyama, Hirofumi Miyazaki, Yun-Ji Lim, Jian Gu, Masaki Ishikawa, Taichi Yoshida, Wanjun Chen, Yuji Owada, Hiroyuki Shibata

Faculty, Staff and Student Publications

Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β). However, GO-Y022 showed less impact on Foxp3+ Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-β. Therefore, naïve CD4+ T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. …

Wnt Signaling In Liver Regeneration, Disease, And Cancer, Gengyi Zou, Jae-Il Park

Faculty, Staff and Student Publications

The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. …

Gankyrin-Mediated Interaction Between Cancer Cells And Tumor-Associated Macrophages Facilitates Prostate Cancer Progression And Androgen Deprivation Therapy Resistance, Guang Peng, Chao Wang, Hongru Wang, Min Qu, Keqin Dong, Yongwei Yu, Yuquan Jiang, Sishun Gan, Xu Gao

Faculty, Staff and Student Publications

Increasing evidence reveals that the interaction between tumor cells and tumor-associated macrophages (TAMs) facilitates the progression of prostate cancer, but the related mechanisms remained unclear. This study determined how gankyrin, a component of the 19S regulatory complex of the 26S proteasome, regulates the progression and androgen deprivation therapy (ADT) resistance of prostate cancer through tumor cell-TAM interactions.

Protein Translation Paradox: Implications In Translational Regulation Of Aging, Harper S Kim, Andrew M Pickering

Faculty, Staff and Student Publications

Protein translation is an essential cellular process playing key roles in growth and development. Protein translation declines over the course of age in multiple animal species, including nematodes, fruit flies, mice, rats, and even humans. In all these species, protein translation transiently peaks in early adulthood with a subsequent drop over the course of age. Conversely, lifelong reductions in protein translation have been found to extend lifespan and healthspan in multiple animal models. These findings raise the protein synthesis paradox: age-related declines in protein synthesis should be detrimental, but life-long reductions in protein translation paradoxically slow down aging and prolong …

The Proteasome: A Key Modulator Of Nervous System Function, Brain Aging, And Neurodegenerative Disease, Kanisa Davidson, Andrew M Pickering

Faculty, Staff and Student Publications

The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays critical roles in nervous system processes. This includes maintenance of cellular homeostasis in neurons. It also includes roles in long-term potentiation via modulation of CREB signaling. The proteasome also possesses roles in promoting dendritic spine growth driven by proteasome localization to the dendritic spines in an NMDA/CaMKIIα dependent manner. Proteasome inhibition experiments in varied organisms has been shown to impact memory, consolidation, recollection and extinction. The proteasome has been further shown to impact circadian rhythm through modulation of …

Evaluation Of Scrub Typhus Surveillance, Alwar District, Rajasthan, India, July-August 2020, Surendra M Prajapati, Kanica Kaushal, Simmi Tiwari, Ajit Shewale, Tushar Nale, Tanzin Dikid

Faculty, Staff and Student Publications

INTRODUCTION: Scrub typhus is one of the most underreported and fatal illnesses accounting for 23% of all febrile illness. Rajasthan reported cases during 2018-2019 in state reporting system but did not report any case to central Integrated Disease Surveillance Programme (IDSP) unit. We evaluated the Scrub typhus surveillance system in Alwar district, Rajasthan, with the objective of describing and evaluating the system and providing evidence-based recommendations to identify gaps.

MATERIAL AND METHODS: In cross-sectional study, we reviewed records and conducted key informant interviews at district- and block-level health facilities. Using US Centers for Disease Control guidelines, we evaluated the system …

Inhibition Of Nox2 Or Nlrp3 Inflammasome Prevents Cardiac Remote Ischemic Preconditioning, Sandra Benavides, Rodrigo Palavecino, Jaime A Riquelme, Luis Montecinos, José Pablo Finkelstein, Paulina Donoso, Gina Sánchez

Faculty, Staff and Student Publications

Introduction: Short episodes of ischemia-reperfusion (IR) in the heart (classical ischemic preconditioning, IPC) or in a limb (remote ischemic preconditioning, RIPC) before a prolonged ischemic episode, reduce the size of the infarct. It is unknown whether IPC and RIPC share common mechanisms of protection. Animals KO for NOX2, a superoxide-producing enzyme, or KO for NLRP3, a protein component of inflammasome, are not protected by IPC. The aim of this study was to investigate if NOX2 or NLRP3 inflammasome are involved in the protection induced by RIPC. Methods: We preconditioned rats using 4 × 5 min periods of IR in the …

Osteoblast-Specific Overexpression Of Nucleolar Protein No66/Riox1 In Mouse Embryos Leads To Osteoporosis In Adult Mice, Qin Chen, Krishna M Sinha, Benoit De Crombrugghe, Ralf Krahe

Faculty, Staff and Student Publications

In previous study, we showed that nucleolar protein 66 (NO66) is a chromatin modifier and negatively regulates Osterix activity as well as mesenchymal progenitor differentiation. Genetic ablation of the NO66 (RIOX1) gene in cells of the Prx1-expressing mesenchymal lineage leads to acceleration of osteochondrogenic differentiation and a larger skeleton in adult mice, whereas mesenchyme-specific overexpression of NO66 inhibits osteochondrogenesis resulting in dwarfism and osteopenia. However, the impact of NO66 overexpression in cells of the osteoblast lineage in vivo remains largely undefined. Here, we generated osteoblast-specific transgenic mice overexpressing a FLAG-tagged NO66 transgene driven by the …

Role Of Sentinel Lymph Node Biopsy For Oral Squamous Cell Carcinoma: Current Evidence And Future Challenges, Sophie S Jang, Morgan E Davis, David R Vera, Stephen Y Lai, Theresa W Guo

Faculty, Staff and Student Publications

Sentinel lymph node biopsy (SLNB) has been used across oncological specialties for prognostication, staging, and identification of occult nodal metastasis. Recent studies demonstrated the potential clinical utility of SLNB in oral cavity squamous cell carcinoma (OCSCC). Elective neck dissection is the current standard of care in early management of OCSCC with depth of invasion greater than 2-4 mm; however, majority of patients ultimately do not have nodal disease on final pathology. SLNB is an alternative procedure widely adopted in early cancer management in many oncological subspecialities. Several considerations such as depth of invasion, nodal mapping, histopathology methods, operator variability, postoperative …

Super-Resolution And Segmentation Deep Learning For Breast Cancer Histopathology Image Analysis, Aniwat Juhong, Bo Li, Cheng-You Yao, Chia-Wei Yang, Dalen W Agnew, Yu Leo Lei, Xuefei Huang, Wibool Piyawattanametha, Zhen Qiu

Faculty, Staff and Student Publications

Traditionally, a high-performance microscope with a large numerical aperture is required to acquire high-resolution images. However, the images' size is typically tremendous. Therefore, they are not conveniently managed and transferred across a computer network or stored in a limited computer storage system. As a result, image compression is commonly used to reduce image size resulting in poor image resolution. Here, we demonstrate custom convolution neural networks (CNNs) for both super-resolution image enhancement from low-resolution images and characterization of both cells and nuclei from hematoxylin and eosin (H&E) stained breast cancer histopathological images by using a combination of generator and discriminator …

Disruption Of Fos Causes Craniofacial Anomalies In Developing Zebrafish, Lorena Maili, Bhavna Tandon, Qiuping Yuan, Simone Menezes, Frankie Chiu, S Shahrukh Hashmi, Ariadne Letra, George T Eisenhoffer, Jacqueline T Hecht

Faculty, Staff and Student Publications

Craniofacial development is a complex and tightly regulated process and disruptions can lead to structural birth defects, the most common being nonsyndromic cleft lip and palate (NSCLP). Previously, we identified FOS as a candidate regulator of NSCLP through family-based association studies, yet its specific contributions to oral and palatal formation are poorly understood. This study investigated the role of fos during zebrafish craniofacial development through genetic disruption and knockdown approaches. Fos was expressed in the periderm, olfactory epithelium and other cell populations in the head. Genetic perturbation of fos produced an abnormal craniofacial phenotype with a hypoplastic oral cavity that …

Protective Role Of Colitis In Inflammatory Arthritis Via Propionate-Producing Bacteroides In The Gut, Hoh-Jeong Shon, Yu-Mi Kim, Kyeong Seog Kim, Jin-Ouk Choi, Sang-Hyun Cho, Sujin An, Se-Hyeon Park, Yong-Joon Cho, Joo-Hong Park, Sang-Uk Seo, Joo-Youn Cho, Wan-Uk Kim, Donghyun Kim

Faculty, Staff and Student Publications

OBJECTIVES: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events.

METHODS: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated …

Ribonuclease 1 Enhances Antitumor Immunity Against Breast Cancer By Boosting T Cell Activation, Ying-Nai Wang, Heng-Huan Lee, Zhou Jiang, Li-Chuan Chan, Gabriel N Hortobagyi, Dihua Yu, Mien-Chie Hung

Faculty, Staff and Student Publications

The secretory enzyme human ribonuclease 1 (RNase1) is involved in innate immunity and anti-inflammation, achieving host defense and anti-cancer effects; however, whether RNase1 contributes to adaptive immune response in the tumor microenvironment (TME) remains unclear. Here, we established a syngeneic immunocompetent mouse model in breast cancer and demonstrated that ectopic RNase1 expression significantly inhibited tumor progression. Overall changes in immunological profiles in the mouse tumors were analyzed by mass cytometry and showed that the RNase1-expressing tumor cells significantly induced CD4+ Th1 and Th17 cells and natural killer cells and reduced granulocytic myeloid-derived suppressor cells, supporting that RNase1 favors an antitumor …

Targeting Immunosuppressive Ly6c+ Classical Monocytes Reverses Anti-Pd-1/Ctla-4 Immunotherapy Resistance, B Leticia Rodriguez, Limo Chen, Yanli Li, Shucheng Miao, David H Peng, Jared J Fradette, Lixia Diao, Jessica M Konen, Frank R Rojas Alvarez, Luisa M Solis, Xiaohui Yi, Aparna Padhye, Laura A Gibson, Joshua K Ochieng, Xiaofei Zhou, Jing Wang, Don L Gibbons

Faculty, Staff and Student Publications

Introduction: Despite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way …

View-Sharing For 4d Magnetic Resonance Imaging With Randomized Projection-Encoding Enables Improvements Of Respiratory Motion Imaging For Treatment Planning In Abdominothoracic Radiotherapy, Ergys Subashi, Li Feng, Yilin Liu, Scott Robertson, Paul Segars, Bastiaan Driehuys, Christopher R Kelsey, Fang-Fang Yin, Ricardo Otazo, Jing Cai

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The accuracy and precision of radiation therapy are dependent on the characterization of organ-at-risk and target motion. This work aims to demonstrate a 4D magnetic resonance imaging (MRI) method for improving spatial and temporal resolution in respiratory motion imaging for treatment planning in abdominothoracic radiotherapy.

MATERIALS AND METHODS: The spatial and temporal resolution of phase-resolved respiratory imaging is improved by considering a novel sampling function based on quasi-random projection-encoding and peripheral k-space view-sharing. The respiratory signal is determined directly from k-space, obviating the need for an external surrogate marker. The average breathing curve is used to optimize …

Blockade Of Mglur5 In Astrocytes Derived From Human Ipscs Modulates Astrocytic Function And Increases Phagocytosis, Izabella B Q De Lima, Pablo L Cardozo, Julia S Fahel, Juliana P S Lacerda, Aline S Miranda, Antônio L Teixeira, Fabiola M Ribeiro

Faculty, Staff and Student Publications

TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 …

The Involvement Of Kynurenine Pathway In Neurodegenerative Diseases, Lais B Martins, Ana L M Silveira, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: A growing body of evidence has shown the involvement of the kynurenine pathway (KP), the primary route of tryptophan (TRP) catabolism, in the pathophysiology of neuropsychiatric disorders.

OBJECTIVE: The study aims to provide a comprehensive and critical overview of the clinical evidence on the KP involvement in the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD), discussing therapeutic opportunities.

METHODS: We searched for studies investigating KP metabolites in human subjects with AD and/or PD.

RESULTS: Postmortem studies showed altered levels of KP metabolites in the brain of AD and PD patients compared with controls. Cross-sectional studies have reported …

C4b-Binding Protein Inhibits Particulate- And Crystalline-Induced Nlrp3 Inflammasome Activation, Damien Bierschenk, Nikolina Papac-Milicevic, Ian P Bresch, Valentina Kovacic, Serena Bettoni, Mateusz Dziedzic, Rick A Wetsel, Susanne Eschenburg, Christoph J Binder, Anna M Blom, Ben C King

Faculty, Staff and Student Publications

Dysregulated NLRP3 inflammasome activation drives a wide variety of diseases, while endogenous inhibition of this pathway is poorly characterised. The serum protein C4b-binding protein (C4BP) is a well-established inhibitor of complement with emerging functions as an endogenously expressed inhibitor of the NLRP3 inflammasome signalling pathway. Here, we identified that C4BP purified from human plasma is an inhibitor of crystalline- (monosodium urate, MSU) and particulate-induced (silica) NLRP3 inflammasome activation. Using a C4BP mutant panel, we identified that C4BP bound these particles

Receptor-Interacting Protein 1 And 3 Kinase Activity Are Required For High-Fat Diet Induced Liver Injury In Mice, Xiaoqin Wu, Rakesh K Arya, Emily Huang, Megan R Mcmullen, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND: The RIP1-RIP3-MLKL-mediated cell death pathway is associated with progression of non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Previous work identified a critical role for MLKL, the key effector regulating necroptosis, but not RIP3, in mediating high fat diet-induced liver injury in mice. RIP1 and RIP3 have active N-terminus kinase domains essential for activation of MLKL and subsequent necroptosis. However, little is known regarding domain-specific roles of RIP1/RIP3 kinase in liver diseases. Here, we hypothesized that RIP1/RIP3 kinase activity are required for the development of high fat diet-induced liver injury.

METHODS:Rip1K45A/K45A and Rip3K51A/K51A kinase-dead mice on a C57BL/6J background and their littermate …

Endothelial Activation And Fibrotic Changes Are Impeded By Laminar Flow-Induced Chk1-Senp2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition, Minh T H Nguyen, Masaki Imanishi, Shengyu Li, Khanh Chau, Priyanka Banerjee, Loka Reddy Velatooru, Kyung Ae Ko, Venkata S K Samanthapudi, Young J Gi, Ling-Ling Lee, Rei J Abe, Elena Mcbeath, Anita Deswal, Steven H Lin, Nicolas L Palaskas, Robert Dantzer, Keigi Fujiwara, Mae K Borchrdt, Estefani Berrios Turcios, Elizabeth A Olmsted-Davis, Sivareddy Kotla, John P Cooke, Guangyu Wang, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear.

METHOD: We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation.

RESULT: …

Possible Molecular Mechanisms Underlying The Development Of Atherosclerosis In Cancer Survivors, Priyanka Banerjee, Julia Enterría Rosales, Khanh Chau, Minh T H Nguyen, Sivareddy Kotla, Steven H Lin, Anita Deswal, Robert Dantzer, Elizabeth A Olmsted-Davis, Hung Nguyen, Guangyu Wang, John P Cooke, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression. Endothelial cell (EC) senescence has been implicated in atherosclerosis and cancer, including among cancer survivors. Treatment modalities for cancer can induce EC senescence, leading to the development of SAS phenotype and subsequent atherosclerosis in cancer survivors. Consequently, targeting senescent ECs displaying the SAS …

Chimeric Rnas Reveal Putative Neoantigen Peptides For Developing Tumor Vaccines For Breast Cancer, Brandon Mistretta, Sakuni Rankothgedera, Micah Castillo, Mitchell Rao, Kimberly Holloway, Anjana Bhardwaj, Maha El Noafal, Constance Albarracin, Randa El-Zein, Hengameh Rezaei, Xiaoping Su, Rehan Akbani, Xiaoshan M Shao, Brian J Czerniecki, Rachel Karchin, Isabelle Bedrosian, Preethi H Gunaratne

Faculty, Staff and Student Publications

INTRODUCTION: We present here a strategy to identify immunogenic neoantigen candidates from unique amino acid sequences at the junctions of fusion proteins which can serve as targets in the development of tumor vaccines for the treatment of breastcancer.

METHOD: We mined the sequence reads of breast tumor tissue that are usually discarded as discordant paired-end reads and discovered cancer specific fusion transcripts using tissue from cancer free controls as reference. Binding affinity predictions of novel peptide sequences crossing the fusion junction were analyzed by the MHC Class I binding predictor, MHCnuggets. CD8+ T cell responses against the 15 peptides were …

Sart-3 Functions To Regulate Germline Sex Determination In C Elegans, Tokiko Furuta, Swathi Arur

Faculty, Staff and Student Publications

Caenorhabditis elegans gene sart-3 was first identified as the homolog of human SART3 ( S quamous cell carcinoma A ntigen R ecognized by T -cells 3). In humans, expression of SART3 is associated with squamous cell carcinoma, thus most of the studies focus on its potential role as a target of cancer immunotherapy (Shichijo et al. 1998; Yang et al. 1999). Furthermore, SART3 is also known as Tip110 (Liu et al. 2002; Whitmill et al. 2016) in the context of HIV virus host activation pathway. Despite these disease related studies, the molecular function of this protein was not revealed until …

Plasma Enzymatic Activity, Proteomics And Peptidomics In Covid-19-Induced Sepsis: A Novel Approach For The Analysis Of Hemostasis, Fernando Dos Santos, Joyce B Li, Nathalia Juocys, Rafi Mazor, Laura Beretta, Nicole G Coufal, Michael T Y Lam, Mazen F Odish, Maria Claudia Irigoyen, Anthony J O'Donoghue, Federico Aletti, Erik B Kistler

Faculty, Staff and Student Publications

Introduction: Infection by SARS-CoV-2 and subsequent COVID-19 can cause viral sepsis. We investigated plasma protease activity patterns in COVID-19-induced sepsis with bacterial superinfection, as well as plasma proteomics and peptidomics in order to assess the possible implications of enhanced proteolysis on major protein systems (e.g., coagulation). Methods: Patients (=4) admitted to the intensive care units (ICUs) at the University of California, San Diego (UCSD) Medical Center with confirmed positive test for COVID-19 by real-time reverse transcription polymerase chain reaction (RT-PCR) were enrolled in a study approved by the UCSD Institutional Review Board (IRB# 190699, Protocol #20-0006). Informed consent was obtained …

Sound Speed Estimation For Distributed Aberration Correction In Laterally Varying Media, Rehman Ali, Trevor M Mitcham, Melanie Singh, Marvin M Doyley, Richard R Bouchard, Jeremy J Dahl, Nebojsa Duric

Faculty, Staff and Student Publications

Spatial variation in sound speed causes aberration in medical ultrasound imaging. Although our previous work has examined aberration correction in the presence of a spatially varying sound speed, practical implementations were limited to layered media due to the sound speed estimation process involved. Unfortunately, most models of layered media do not capture the lateral variations in sound speed that have the greatest aberrative effect on the image. Building upon a Fourier split-step migration technique from geophysics, this work introduces an iterative sound speed estimation and distributed aberration correction technique that can model and correct for aberrations resulting from laterally varying …

Comparison Of Pharmacological Inhibitors Of Lysine-Specific Demethylase 1 In Glioblastoma Stem Cells Reveals Inhibitor-Specific Efficacy Profiles, Lea M Stitzlein, Achintyan Gangadharan, Leslie M Walsh, Deokhwa Nam, Alexsandra B Espejo, Melissa M Singh, Kareena H Patel, Yue Lu, Xiaoping Su, Ravesanker Ezhilarasan, Joy Gumin, Sanjay Singh, Erik Sulman, Frederick F Lang, Joya Chandra

Faculty, Staff and Student Publications

INTRODUCTION: Improved therapies for glioblastoma (GBM) are desperately needed and require preclinical evaluation in models that capture tumor heterogeneity and intrinsic resistance seen in patients. Epigenetic alterations have been well documented in GBM and lysine-specific demethylase 1 (LSD1/KDM1A) is amongst the chromatin modifiers implicated in stem cell maintenance, growth and differentiation. Pharmacological inhibition of LSD1 is clinically relevant, with numerous compounds in various phases of preclinical and clinical development, but an evaluation and comparison of LSD1 inhibitors in patient-derived GBM models is lacking.

METHODS: To assess concordance between knockdown of LSD1 and inhibition of LSD1 using a prototype inhibitor in …

Cannabis Use Disorder, Suicide Attempts, And Self-Harm Among Adolescents: A National Inpatient Study Across The United States, Adeolu Funso Oladunjoye, Elijah Li, Kammarauche Aneni, Edore Onigu-Otite

Faculty, Staff and Students Publications

Background: Suicide is among the top three causes of adolescent mortality. There is a scarcity of research examining cannabis use and suicidal behavior in adolescents.

Objectives: To determine the association between cannabis use disorder (CUD) and suicide attempt/self-harm in a hospitalized sample of adolescents.

Methods: We conducted a cross-sectional observation study using data from the Nationwide Inpatient Sample collected over four years from January 1, 2016, through December 31, 2019. We included adolescents aged 10-19 hospitalized during the above period (N = 807,105). The primary outcome was suicide attempt/self-harm and the main predictor was CUD. The International Classification of Diseases …