Amino Acids, Peptides, and Proteins Commons^™

The Multifunctional Ascorbate Peroxidase Moapx1 Secreted By Magnaporthe Oryzae Mediates The Suppression Of Rice Immunity, Muxing Liu, Ziqian Guo, Jiexiong Hu, Yuke Chen, Fang Chen, Weizhong Chen, Wenya Wang, Boyang Ye, Zhixiang Yang, Gang Li, Xinyu Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Fungi secrete effector proteins, including extracellular redox enzymes, to inhibit host immunity. Redox enzymes have been hypothesized to inhibit host reactive oxygen species (ROS); however, how they suppress host immunity remains unknown. We characterized an extracellular ascorbate peroxidase (MoApx1) that is secreted into rice chloroplasts by the rice blast fungus Magnaporthe oryzae. MoApx1 displays multifunctional capabilities that significantly contribute to fungal virulence. Firstly, MoApx1 neutralizes host-derived H2O2 within the chloroplast through its peroxidase activity, thereby inhibiting chloroplast ROS (cROS)-mediated defense responses. Secondly, MoApx1 targets the photosystem I subunit OsPsaD, disrupting photosynthetic electron transport to further suppress cROS production. Most importantly, …

Ovarian Cancer G Protein-Coupled Receptor-1 Signaling Bias Dictates Anti-Contractile Effect Of Benzodiazepines On Airway Smooth Muscle, Dominic R. Villalba, Arun K. Jannu, Elham Javed, Isha Dandekar, Ruping Wang, Deepak A. Deshpande, Steven S. An, Reynold A. Panettieri, Dale D. Tang, Raymond B. Penn, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

BACKGROUND: We recently reported that the ovarian cancer G protein-coupled receptor-1 (OGR1) can be pharmacologically biased with specific benzodiazepines to couple with distinct heterotrimeric G proteins in human airway smooth muscle (ASM) cells. Lorazepam stimulated both G

METHODS: Models of histamine (His) -stimulated contraction included imaging of ex vivo human precision cut lung slices (hPCLS) and Magnetic Twisting Cytometry (MTC) analysis of human ASM cell stiffness. To explore mechanisms of regulation, we examined effects on myosin light chain (pMLC) phosphorylation and PKA activity in primary human ASM cultures, as well as actin cytoskeleton integrity as defined by changes in the …

The Correlation Between A Methylenetetrahydrofolate Reductase Deficiency In Autism Spectrum Disorder Patients And The Presence Of Mental Health Disorders, Hinal Joshi, Andrea Iannuzzelli

Rowan-Virtua Research Day

• Currently little literature exists on connection between Methylenetetrahydrofolate reductase (MTHFR) deficiency and mental health disorders

• Reduced enzyme activity associated with certain MTHFR variants contributes to altered folate metabolism, elevated homocysteine levels, and disrupted DNA methylation, all of which are implicated in mental health disorders

• Identifying genetic risk factors could facilitate earlier diagnosis and intervention, leading to improved outcomes

• Relevant results could help reduce stigma and promote greater understanding of challenges faced by patients on the spectrum

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …

Structural Insights Into The Function, Dysfunction And Modulation Of Kv3 Channels, Manuel Covarrubias, Qiansheng Liang, Linh Nguyen-Phuong, Kyle J. Kennedy, Tyler D. Alexander, Ms, Andrew Sam

Department of Neuroscience Faculty Papers

The third subfamily of voltage-gated K⁺ (Kv) channels includes four members, Kv3.1, Kv3.2, Kv3.3 and Kv3.4. Fast gating and activation at relatively depolarized membrane potentials allows Kv3 channels to be major drivers of fast action potential repolarization in the nervous system. Consequently, they help determine the fast-spiking phenotype of inhibitory interneurons and regulate fast synaptic transmission at glutamatergic synapses and the neuromuscular junction. Recent studies from our group and a team of collaborators have used cryo-EM to demonstrate the surprising gating role of the Kv3.1 cytoplasmic T1 domain, the structural basis of a developmental epileptic encephalopathy caused by the …

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …

Hdac5 Enzymatic Activity Regulates Scn4b Expression To Control Relapse-Like Cocaine Seeking, Daniel J. Wood

MUSC Theses and Dissertations

Substance Use Disorder (SUD) is a relapsing disorder characterized by repeated seeking and use of psychoactive substances despite negative consequences to the individual. Epigenetic changes within the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) are thought to underly the lasting propensity to relapse in SUD. The epigenetic enzyme histone deacetylase 5 (HDAC5) in NAc MSNs limits the formation of reward-cue associations in rodent models of drug seeking, but not sucrose seeking, leading to decreased relapse-like behavior. However, whether HDAC5 reduces drug seeking behavior through its own deacetylase activity or through the recruitment of co-repressors is unknown. Furthermore, these …

Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold

Department of Medicine Faculty Papers

Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, the mechanisms by which these processes develop and interact within the growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in these progenitors results in regionally restricted and developmentally arrested microglia that persist into adulthood. In the absence of autocrine TGFβ1 signaling, microglia adopt a similar phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the canonical TGFβ signal transducers …

Investigating The Impact Of Tirzepatide Treatment On Alcohol And Cigarette Consumption, Yvannia Gray, Benjamin Latey, Hayden Mcaffee, Karissa Mccown, Seth Maki, Victoria Nguyen, Andrew Payne

Annual Research Symposium

No abstract provided.

Skeletal And Dental Tissue Mineralization: The Potential Role Of The Endoplasmic Reticulum/Golgi Complex And The Endolysosomal And Autophagic Transport Systems, Irving M. Shapiro, Makarand V. Risbud, Tengteng Tang, William J. Landis

Department of Orthopaedic Surgery Faculty Papers

This paper presents a review of the potential role of the endoplasmic reticulum/Golgi complex and intracellular vesicles in mediating events leading to or associated with vertebrate tissue mineralization. The possible importance of these organelles in this process is suggested by observations that calcium ions accumulate in the tubules and lacunae of the endoplasmic reticulum and Golgi. Similar levels of calcium ions (approaching millimolar) are present in vesicles derived from endosomes, lysosomes and autophagosomes. The cellular level of phosphate ions in these organelles is also high (millimolar). While the source of these ions for mineral formation has not been identified, there …

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura^®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …

The Central Role For Troponin C Amino-Terminal ⍺-Helix In Vertebrate Thin Filiment Ca²⁺-Activation, Yun Shi, Lauren A. Blackwell, Ryan K. Schroy, B. Max Cleland, Cristina M. Risi, Michelle S. Parvatiyar, Jose R. Pinto, Vitold E. Galkin, P. Bryant Chase

Department of Biomedical and Translational Sciences Faculty Publications

Troponin C (TnC) is the Ca²⁺-sensing subunit of troponin that is responsible for activating thin filaments in striated muscle, and, in turn, for regulating the systolic and diastolic contractile function of cardiac muscle. The secondary structure of vertebrate TnC is mainly composed of α-helices, with nine helices named sequentially, starting from the amino terminus, from N to A–H. The N-helix is a 12-residue-long α-helix located at the extreme amino terminus of the protein and is the only helical structure that does not participate in forming Ca²⁺-binding EF-hands. Evolutionarily, the N-helix is found only in TnC from mammalian species and most …

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

Inflammatory Mediators And The Rage Pathway In Placental Tissues Of Pregnancies Complicated By Severe Preeclampsia, Neelima Chandra, Thomas D. Kimble, Kathleen R. Heim, Sharon M. Anderson, Andrew P. Wong, Andrea R. Thurman, Gustavo F. Doncel

CONRAD Publications

Introduction: Preeclampsia (PE) is a complex multisystem disorder of pregnancy associated with abnormal placentation, vascular anomalies, and systemic inflammation and hypertension. Previous research assessing inflammatory triggers of the condition used plasma, amniotic fluid, or explant samples. Studies using placental tissue from either vaginal or cesarean deliveries are confined to semiquantitative analysis using subjective scoring methods and generally involve a small sample size.

Methods: In this study, we have quantified the expression of inflammatory mediators by immunohistochemical image analysis of archived placental tissues obtained from cesarean delivery of preeclamptic, chorioamnionitic, and normal pregnancies.

Results: Among the inflammatory mediators, we found a …

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …

Automating The Amino Acid Identification In Elliptical Dichroism Spectrometer With Machine Learning, Ridhanya Sree Balamurugan, Yusuf Asad, Tommy Gao, Dharmakeerthi Nawarathna, Umamaheswara Rao Tida, Dali Sun

Electrical & Computer Engineering Faculty Publications

Amino acid identification is crucial across various scientific disciplines, including biochemistry, pharmaceutical research, and medical diagnostics. However, traditional methods such as mass spectrometry require extensive sample preparation and are time-consuming, complex and costly. Therefore, this study presents a pioneering Machine Learning (ML) approach for automatic amino acid identification by utilizing the unique absorption profiles from an Elliptical Dichroism (ED) spectrometer. Advanced data preprocessing techniques and ML algorithms to learn patterns from the absorption profiles that distinguish different amino acids were investigated to prove the feasibility of this approach. The results show that ML can potentially revolutionize the amino acid analysis …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …

The Life And Discoveries Of Yellapragada Subbarow, Nikhil R, Varuni Pragya, Subramanian Ramaswamy, Shiva Prasad B N, Mahabaleshwar Mamadapur

Digital Journal of Clinical Medicine

Dr. Yellapragada Subbarow was a researcher, teacher, and a wizard of wonder drugs who constantly made efforts in the discoveries/ inventions such as vitamins, anti-vitamins, antibiotics, and many more by disentangling the mysteries of nature for the betterment of the people. He inspired the youngsters to take up the challenges and to stand up above mediocrity. The reward for his achievement was delayed. The article describes a true humanist's journey, discoveries, and his achievements that are largely unknown to date.

Role Of Myeloid Cell-Specific Adenylyl Cyclase Type 7 In Lipopolysaccharide- And Alcohol-Induced Immune Responses, Yawen Hu, Sonika Patial, Yogesh Saini, Masami Yoshimura

School of Graduate Studies Faculty Publications

Clinical and experimental evidence indicates that alcohol use causes various abnormalities in the immune system and compromises immune functions. However, the mechanistic understanding of ethanol’s effects on the immune system remains limited. Cyclic AMP (cAMP) regulates multiple processes, including immune responses. Earlier research indicated that type 7 adenylyl cyclase (AC7) regulates the immune system and is highly responsive to ethanol. Therefore, we hypothesized that AC7 is a central player in regulating the effects of alcohol on innate immune responses. To test this hypothesis, we utilized a myeloid lineage-specific AC7 KO mouse model and compared the effects of acute and chronic …

Functions Of Tam Receptors And Ligands Protein S And Gas6 In Atherosclerosis And Cardiovascular Disease, Teagan Prouse, Samarpan Majumder, Rinku Majumder

School of Medicine Faculty Publications

Atherosclerosis and cardiovascular disease are associated with high morbidity and mortality in industrialized nations. The Tyro3, Axl, and Mer (TAM) family of receptor tyrosine kinases is involved in the amplification or resolution of atherosclerosis pathology and other cardiovascular pathology. The ligands of these receptors, Protein S (PS) and growth arrest specific protein 6 (Gas6), are essential for TAM receptor functions in the amplification and resolution of atherosclerosis. The Axl-Gas6 interaction has various effects on cardiovascular disease. Mer and PS dampen inflammation, thereby protecting against atherosclerosis progression. Tyro3, the least studied TAM receptor in cardiovascular disease, appears to protect against fibrosis …

Meca In Streptococcus Mutans Is A Multi-Functional Protein, Kassapa Ellepola, Robert C. Shields, Jessica K. Kajfasz, Hua Zhang, Jose A. Lemos, Hui Wu, Zezhang T. Wen

School of Dentistry Faculty Publications

UNLABELLED: Our recent studies have shown that deficiency of MecA in Streptococcus mutans significantly affects cell division, growth, and biofilm formation. In this study, an in vitro mixed-species model, proteomics, and affinity pull-down assays were used to further characterize the MecA-mediated regulation in S. mutans. The results showed that compared with the wild type, UA159, the mecA mutant significantly reduced its production of glucans and weakened its ability to facilitate mixed-species biofilm formation. Relative to the wild type, the mecA mutant also displayed unique characteristics, including colony morphology, growth rate, and biofilm formation that did not fully resemble any of …

Metallomic Approach To Mercury And Selenium In The Liver Tissue Of Psectrogaster Amazonica And Raphiodon Vulpinus From The Brazilian Amazon, Izabela Bataglioli, José Vieira, Joyce Da Siva, Luane Andrade, Victor Faria, Rebeca Corcoba, Ronaldo De Almeida, Luiz Zara, Marília Buzalaf, Jiri Adamec, Pedro Padilha

School of Medicine Faculty Publications

This paper reports the results of a mercury (Hg) and selenium (Se) metallomic study in the liver tissues of Psectrogaster amazonica and Raphiodon vulpinus from the Brazilian Amazon. Two-dimensional electrophoresis, graphite furnace atomic absorption spectrometry, and liquid chromatography-tandem mass spectrometry were performed. Hg and Se determinations allowed the calculation of Hg:Se and Se:Hg molar ratio and Se values for health benefits (Se HBVs). The Se:Hg values were >1 for both fish species, whereas the Se HBVs were >5 for P. amazonica and >10 for R. vulpinus, indicating that both possess Se reserves to control Hg toxicity. The metallomic data allowed …

Identification Of The N-Terminal Residues Responsible For The Differential Microdomain Localization Of Cyp1a1 And Cyp1a2, Robert M. Fuchs, James R. Reed, J. Patrick Connick, Markéta Paloncýová, Martin Šrejber, Petra Čechová, Michal Otyepka, Marilyn K. Eyer, Wayne L. Backes

School of Graduate Studies Faculty Publications

The endoplasmic reticulum is organized into ordered regions enriched in cholesterol and sphingomyelin, and disordered microdomains characterized by more fluidity. Rabbit CYP1A1 and CYP1A2 localize into disordered and ordered microdomains, respectively. Previously, a CYP1A2 chimera containing the first 109 amino acids of CYP1A1 showed altered microdomain localization. The goal of this study was to identify specific residues responsible for CYP1A microdomain localization. Thus, CYP1A2 chimeras containing substitutions from homologous regions of CYP1A1 were expressed in HEK 293T/17 cells, and the localization was examined after solubilization with Brij 98. A CYP1A2 mutant with the three amino acids from CYP1A1 (VAG) at …

Transcription And Post-Translational Mechanisms: Dual Regulation Of Adiponectin-Mediated Occludin Expression In Diabetes, Yanru Duan, Demin Liu, Huahui Yu, Shihan Zhang, Yihua Xia, Zhiyong Du, Yanwen Qin, Yajing Wang, Xin-Liang Ma, Huirong Liu, Yunhui Du

Department of Emergency Medicine Faculty Papers

BACKGROUND: Occludin, a crucial component of tight junctions, has emerged as a promising biomarker for the diagnosis of acute ischemic disease, highlighting its significant potential in clinical applications. In the diabetes, Occludin serves as a downstream target gene intricately regulated by the adiponectin (APN) signaling pathway. However, the specific mechanism by which adiponectin regulates Occludin expression remains unclear.

METHODS AND RESULTS: Endothelial-specific Ocln knockdown reduced APN-mediated blood flow recovery after femoral artery ligation and nullified APN's protection against high-fat diet (HFD)-triggered apoptosis and angiogenesis inhibition in vivo. Mechanically, we have meticulously elucidated APN's regulatory role in Occludin expression through a …

Liposomal Fba And Met6 Peptide Vaccination Protects Mice From Disseminated Candidiasis, Wei-Chiao Huang, Karen Eberle, Jonothan Rosario Colon, Jonathan F. Lovell, Hong Xin

School of Graduate Studies Faculty Publications

UNLABELLED: Epitopes from the cell surface proteins Fba and Met6 are putative vaccine targets for invasive candidiasis. Here, we describe a vaccine approach in which short peptides derived from Fba and Met6 are used in spontaneous nanoliposome antigen particle (SNAP) format. SNAP was enabled by the interaction of cobalt porphyrin phospholipid in liposomes with three histidine residues on the N-terminus of synthetic short peptide immunogens from Fba (F-SNAP), Met6 (M-SNAP), or bivalent Fba and Met6 (FM-SNAP). Liposomes were adjuvanted with synthetic monophosphoryl lipid and QS-21. In mice, immunization with F-SNAP, M-SNAP, or FM-SNAP induced antigen-specific IgG responses and mixed Th1/Th2 …

Csf1r Inhibition Depletes Brain Macrophages And Reduces Brain Virus Burden In Siv-Infected Macaques, Diana G. Bohannon, Laurent D. Zablocki-Thomas, Evan S. Leung, Jinbum K. Dupont, Julian B. Hattler, Jolanta Kowalewska, Miaoyun Zhao, Jiangtao Luo, Marco Salemi, Angela M. Amedee, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

School of Graduate Studies Faculty Publications

Perivascular macrophages (PVMs) and, to a lesser degree, microglia are targets and reservoirs of HIV and simian immunodeficiency virus (SIV) in the brain. Previously, we demonstrated that colony-stimulating factor 1 receptor (CSF1R) in PVMs was upregulated and activated in chronically SIV-infected rhesus macaques with encephalitis, correlating with SIV infection of PVMs. Herein, we investigated the role of CSF1R in the brain during acute SIV infection using BLZ945, a brain-penetrant CSF1R kinase inhibitor. Apart from three uninfected historic controls, nine Indian rhesus macaques were infected acutely with SIVmac251 and divided into three groups (n = 3 each): an untreated control and …

Loss Of Hormone Receptor Expression After Exposure To Fluid Shear Stress In Breast Cancer Cell Lines, Jonathan Cuccia, Braulio Andres Ortega Quesada, Ethan P. Littlefield, Alejandra M. Ham, Matthew E. Burow, Adam T. Melvin, Elizabeth C. Martin

School of Medicine Faculty Publications

Following metastatic spread, many hormone receptor positive (HR(+)) patients develop a more aggressive phenotype with an observed loss of the HRs estrogen receptor (ER) and progesterone receptor (PR). During metastasis, breast cancer cells are exposed to high magnitudes of fluid shear stress (FSS). Unfortunately, the role for FSS on the regulation of HR expression and function during metastasis is not fully understood. This study was designed to elucidate the impact of FSS on HR(+) breast cancer. Utilizing a microfluidic platform capable of exposing breast cancer cells to FSS that mimics in situ conditions, we demonstrate the impact of FSS exposure …

Advancing Risk Stratification In Hfpef: Unveiling The Potential Of Cardiac Fibrosis Markers For Early Diagnosis And Enhanced Patient Outcomes, Mariam Abdeen

Rowan-Virtua Research Day

Heart failure with preserved ejection fraction (HFpEF) challenges clinicians due to its diverse presentation and limitations in traditional diagnostic criteria. This study delves into the potential of cardiac fibrosis markers like galectin-3, NT-proBNP, and trimethylamine N-oxide (TMAO) to enhance diagnostic precision and patient outcomes in HFpEF. A systematic review of sixteen relevant studies revealed that these biomarkers offer promise for early detection and improved risk assessment. For instance, TMAO indicates systemic implications of HFpEF, while galectin-3 shows predictive value across heart failure types. Additionally, machine-learning models incorporating multiple biomarkers predict significant risk of adverse outcomes. Despite these advances, challenges like …