Digital Commons Network^™

Omega-3–Rich Fish Oil Lipid Emulsions Significantly Prevent Sepsis-Driven Mesenteric Hypoperfusion And Multi-Organ Injury In Murine Models, Gökşen Öz, Esi̇n Özçelebi̇, Ayşe Yeşi̇m Göçmen, Cenk Sükmensüer, Selma Yildirim, Arzu Topeli̇, Alper Bektaş İski̇t

Turkish Journal of Medical Sciences

Background/aim: Parenteral feeding is used in critically ill patients when enteral nutrition is inadequate or intolerable, and the gastrointestinal tract is not functioning properly. Lipid emulsions play a major role in parenteral nutrition because they supply necessary fatty acids and a high-calorie density. We investigated the effects of parenteral lipid emulsions on mesenteric perfusion, inflammation-induced oxidation, and organ damage in lipopolysaccharide-induced mice endotoxemia model.

Materials and methods: In septic mice, organ damage induced by lipopolysaccharide was assessed by histopathology and biochemical examination. Additionally, an ultrasonic blood flowmeter was used to measure the impact of lipid emulsions on mesenteric blood flow. …

The Role Of Mitochondrial And Lysosomal Damage In Neurotoxicity From Parkinson 'S-Related Environmental Exposures, Neda Ilieva

ETDs from 2020-2029

Parkinson's disease (PD) is a progressive motor neurodegenerative disorder with a predominantly idiopathic etiology. More recently, however, the contribution of exogenous risk factors such as environmental contaminants has become of interest. Some endogenous genetic risk factors have been well characterized, but the mechanisms by which exogenous insults, such as environmental contaminants, drive dopaminergic neurodegeneration remain incompletely understood. This dissertation will address how environmental contaminants converge on mitochondrial and lysosomal dysfunction to activate parallel neurotoxic signaling pathways, with a focus on the LRRK2 kinase and the cGAS-STING innate immune pathway. Chapter 2 demonstrates that pharmacological inhibition of LRRK2 kinase activity protects …

Hp1bp3 Loss Links Chromatin Reorganization To Metabolic Vulnerability In Glioma, Brittney Lozzi, Taylor A Gatesman, Pushan Dasgupta, Debosmita Sardar, Yeunjung Ko, Chenyu Mao, Hsiao-Chi Chen, Rachel N Curry, Dongjoo Choi, Carrie A Mohila, Melissa L Bondy, Ganesh Rao, Marco Gallo, Sameer Agnihotri, Benjamin Deneen

Duncan NRI Faculty and Staff Publications

High-grade gliomas (HGGs) are aggressive brain tumors with poor prognosis, driven in part by metabolic and epigenetic adaptations. Methionine metabolism supports HGG growth by supplying S-adenosylmethionine for methylation reactions, yet how nutrient availability influences chromatin organization in HGG remains incompletely understood. Using an immunocompetent mouse model of HGG, we found that dietary methionine restriction reduced tumor proliferation, extended survival, and induced partial nuclear inversion. We identified Hp1bp3 as a key regulator of tumor growth that functions by interacting with nuclear tethering proteins to mediate chromatin reorganization. Loss of Hp1bp3 results in the upregulation of histone demethylases leading to selective depletion …

Autophagic Flux Blockade Under Hypocapnia Reveals Co2-Sensitive Regulation Of Autophagy-Lysosome Homeostasis, Naghmana Ashraf, Zhen Sun, Jeanine L Van Nostrand

Faculty, Staff and Students Publications

Hypocapnia, a reduction in partial pressure of carbon dioxide (CO2), commonly occurs in clinical contexts such as mechanical ventilation, panic disorder, and brain injury, yet its impact on cellular homeostasis remains poorly understood. Given the central role of autophagy in stress adaptation, we investigated how low CO2 influences autophagic flux and lysosomal function. We found that hypocapnia induces autophagosome accumulation while impairing cargo degradation, indicating a blockade in autophagic flux. This response was accompanied by increased lysosome biogenesis but, paradoxically, reduced autophagosome-lysosome fusion and lysosomal proteolytic activity. Mechanistically, hypocapnia promoted TFE3 dephosphorylation and nuclear translocation, driving transcriptional activation of lysosomal …

Macropinocytosis Inhibition Attenuates Profibrotic Responses In Lung Fibroblasts And Pulmonary Fibrosis Models, Ivan O Rosas, Aaron K Mcdowell-Sanchez, Santiago Sanchez, Juan D Cala-Garcia, Alan R Waich Cohen, Elisa Ruiz-Echartea, Scott A Ochsner, Daniel C Kraushaar, Lindsay J Celada, Dandan Sun, Francesca Polverino, Cristian Coarfa, Neil J Mckenna, Konstantin Tsoyi

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disorder with limited treatment options. Macropinocytosis is one of the key cellular processes involved in nutrient consumption from the extracellular environment under stress conditions. Here, we studied the role of macropinocytosis in experimental pulmonary fibrosis models. We found that macropinocytosis is increased in human lung fibroblasts (HLFs) derived from patients with IPF. The inhibition of macropinocytosis with 5-(n-ethyl-n-isopropyl)-amiloride (EIPA) inhibited profibrotic responses in IPF-derived and TGF-β1-stimulated HLFs and reduced pulmonary fibrosis in bleomycin-injured (Bleo-injured) mice. EIPA exerted its antifibrotic effects by regulating amino acid uptake, mammalian target of rapamycin complex 1 …

Differential Roles Of Moesin And Vasp In Β-Catenin-Associated Networks During Zebrafish Heart Regeneration, Allen Rutman

Undergraduate Theses, Capstones, and Recitals

With cardiovascular disease remaining as the leading cause of mortality worldwide, it is largely due to the limited regenerative capacity of the human heart. However, zebrafish (Danio rerio) can fully regenerate cardiac tissue following injury, providing a valuable model for studying the mechanisms of heart repair. To investigate these mechanisms, we used proteomics methods in the past. Proximity labeling is a technique that identifies proteins based on their physical proximity to a protein of interest. It can be applied in organisms and in living cells (Roux et al., 2012; Cho et al., 2020). We used proximity labeling to characterize protein …

Single-Nucleus Profiling Reveals A Core Disease Signature And Cell Type-Specific Vulnerabilities In Early Rett Syndrome, Yan Li, Ashley G Anderson, Guantong Qi, Sih-Rong Wu, Jean-Pierre Revelli, Hu Chen, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Rett syndrome (RTT) is an X-linked neurological disorder caused by MECP2 mutations, creating distinct cellular environments in females (mosaic) versus males (nonmosaic). Despite female patients representing most cases, how mosaicism contributes molecularly to RTT pathogenesis, particularly in presymptomatic stages, remains poorly understood. To address this question, we profiled hippocampal transcriptomes of young female and male RTT mice using bulk and single-nucleus RNA sequencing. We identified a core disease signature of consistently dysregulated genes only in MeCP2− cells across RTT models. Moreover, we uncovered non–cell autonomous effects exclusively in female MeCP2+ excitatory neurons, suggesting that these circuits are more vulnerable early …

Artificial Intelligence In Biomedical Scientific Publishing, Tomasz J Guzik, Victor Aboyans, Stefan Agewall, Steven Bailey, Adrian Baranchuk, Magnus Bäck, Michael Böhm, Robert O Bonow, George W Booz, Giuseppe Boriani, Biykem Bozkurt, Nico Bruining, Davide Capodanno, Çetin Erol, Péter Ferdinandy, Alessia Gimelli, Gerd Heusch, Thomas Kahan, Chim Choy Lang, Gerald Maurer, Robert J Mentz, Marco Metra, Philip Moons, Daniel Piskorz, Massimo Piepoli, Piotr Ponikowski, Alexandra Popma, Bianca Rocca, Juan Sanchis Fores, Philipp Sommer, Rhian M Touyz, Zoltan Ungvari, Pascal Vranckx, Joseph A Hill, Thomas F Lüscher, Filippo Crea

Faculty, Staff and Students Publications

Artificial intelligence is now embedded across the scientific research and publishing ecosystem, influencing discovery, analysis, knowledge translation, authorship, peer review, and editorial workflows. In cardiovascular and biomedical sciences, these developments offer substantial opportunities to accelerate knowledge generation, integrate complex datasets, and improve efficiency and consistency. At the same time, they introduce new risks related to bias, transparency, data integrity, and authorship responsibility, potentially endangering trust in the scientific record. This commentary examines the evolving role of AI in biomedical publishing, with particular attention to generative models and machine learning tools. We review both benefits and limitations, highlight risks such as …

Mapping The Neuroexposome: Integrative Analysis Of Dementia Risk Factors Through Multi-Omics And Environmental Profiling In The Egyptian Population., Mai Ahmed Saadzaghloul Othman

Theses and Dissertations

Background: Dementia represents one of the most pressing public health challenges of the twenty-first century, with the global burden projected to reach 153 million cases by 2050. Egypt, as the most populous Arab nation, faces a corresponding rise in age-related diseases, yet comprehensive data from low- and middle-income countries remain severely limited. The neuroexposome framework, integrating genetic susceptibility, environmental exposures, and metabolic alterations, offers a powerful strategy to characterize the complex interplay between internal and external risk factors for Alzheimer's disease (AD) and Alzheimer's disease Related Dementias (ADRD).

Objectives: This thesis aimed to: (1) examine the distribution of APOE alleles …

The Gut Microbiome, The Gut-Brain Axis, And College Student Well-Being, Idi Mckay

University Honors Theses

This literature review examines how diet, stress, environmental exposure, and food accessibility may influence college students' mental health and academic performance through the gut microbiome and the Gut-Brain Axis (GBA). Current microbiome research often focuses on early childhood development, clinical disease populations, or older adults, while overlooking college-age students who experience significant social, environmental, and biological transitions. College students frequently face food insecurity, irregular eating patterns, chronic stress, inconsistent sleep schedules, and reduced access to nutrient-dense foods, all of which may influence microbial diversity and overall gut health.

This thesis explores how modern campus environments and lifestyle factors may contribute …

Statewide Multi-Year Wastewater Sequencing Reveals Dual Origins Of Hiv-1 Signal, Justin R Clark, Dylan Chirman, Harihara Prakash, Austen Terwilliger, Marlene Mcneese, Matt Ross, Mike Tisza, Sara J Javornik Cregeen, Loren Hopkins, Jennifer Deegan, Catherine L Troisi, Eric Boerwinkle, Kristina Mena, Fuqing Wu, Jason T Kimata, Marc Johnson, Devon Gregory, Faith E Fletcher, Thomas P Giordano, Anthony W Maresso

Faculty, Staff and Students Publications

Human immunodeficiency virus 1 (HIV-1) is a retrovirus which has infected 90 million people and resulted in over 40 million deaths. Despite advances in diagnostics, treatment, and prophylaxis, HIV-1 continues to spread due to undiagnosed and untreated infections. Traditional monitoring methods are ineffective when access to testing is limited or people do not seek care, particularly given the long period between infection and symptom onset, allowing undetected transmission to continue. Here, we use a hybrid-capture sequencing approach to track HIV-1 signal in municipal wastewater in 15 different cities over nearly 3 years. We obtain near-complete genomic coverage of HIV-1, enabling …

Immunoinformatic Based Development Of A Multi-Epitope Precision Vaccine Targeting Glycoprotein And Rdrp Of Oropouche Virus: An Innovative Approach To Counter Emerging Public Health Threats, Mohammed Alissa, Muhammad Suleman

Saudi Medical Journal

Objectives: To design high immunogenic vaccine against the Oropouche virus (OROV). The OROV is a neglected arbovirus endemic to Central and South America, causes oropouche fever, which can progress to severe complications such as meningitis and hemorrhagic symptoms.

Methods: We utilized immunoinformatic and molecular dynamic simulation approaches to design highly immunogenic vaccines against OROV. This observational study, carried out between January and August 2024 in Saudi Arabia. As it involves an in-silico method, ethical consent was not required.

Results: Docking analysis confirmed the stable interaction of the designed vaccines with human toll-like receptors (TLR)-3, producing binding scores of –300.78, –306.19, …

Interleukin-6 Inhibition For Patients With Acute Myocardial Infarction: A Systematic Review And Meta-Analysis, Mohammed Y. Alasmary, Mohammed J. Almalki, Faisal H. Almalki, Waleed D. Khubzan, Mohammed H. Rajab, Mohammed S. Almalki, Hussam A. Almalki, Omar M. Alsuwat, Hussam M. Alghannami

Saudi Medical Journal

Objective: To explore the outcomes associated with interleukin-6 (IL-6) pathway blockade, using tocilizumab, in patients with ST-elevation myocardial infarction (STEMI) and non (NSTEMI). Acute myocardial infarction (AMI) denotes myocardial necrosis due to ischemia and presents in distinct electrocardiographic phenotypes. Inflammation driven by IL-6 contributes to ischemia-reperfusion injury, with tocilizumab showing promise in reducing myocardial damage and improving outcomes.

Methods: This work followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Framework and was registered in international prospective register of systematic reviews (PROSPERO). Relevant studies were identified through structured searches of PubMed, MEDLINE, the Cochrane Library, and Google Scholar up …

Effect Of Anesthetic Agents On Middle Ear Pressure: Systematic Review And Meta-Analysis, Nasser Almujaiwel, Reem Alkublan, Latifah Almakoshi

Saudi Medical Journal

Objective: To assess and compare the effects of these agents on middle ear pressure (MEP). Anesthetic agents can significantly alter MEP, which is a critical factor in middle ear surgeries that require stability to prevent complications. Different anesthetics, including inhalational and intravenous agents, have varying effects on MEP.

Methods: A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Scopus, following preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Studies that evaluated MEP changes before and after anesthesia using tympanometry were included. Relevant data, such as anesthetic type, patient demographics, MEP measurements, and reported complications, were …

In Vivo Orf Overexpression Screening Identifies Ccn4 As A Regulator Of Glioblastoma Growth Validated Across Multiple Models, Pushan Dasgupta

Faculty, Staff and Students Publications

Despite current multimodal therapies for glioblastoma (GBM), its prognosis remains grim. Thus, a tremendous need exists to identify new genetic drivers that may serve as potential therapeutic targets in glioblastoma (GBM). We describe an in vivo overexpression screening strategy to identify drivers of glioblastoma where we have leveraged TCGA datasets to conduct a functional genomics screen of prioritized open reading frames (ORFs) that are overexpressed and/or amplified in GBM. To interrogate these potential drivers within a more relevant physiological context, the screening was accomplished in vivo in an orthotopic patient-derived glioma stem-like cell (GSC) model. Among 5 positive "hits" from …

Notch1 Acts As A Tumor Suppressor That Induces Early Differentiation In Head And Neck Cancer, Chenfei Huang, Shhyam Moorthy, Qiuli Li, Kazi M Ahmed, Kalil Saab, Defeng Deng, Jiping Wang, Xiayu Rao, Jiexin Zhang, Yuanxin Xi, Jing Wang, Zhiyi Liu, Noriaki Tanaka, David A Wheeler, Eve Shinbrot, Rami Saade, Curtis R Pickering, Tong-Xin Xie, Adel K El-Naggar, Abdullah A Osman, Kunal Rai, Patrick A Zweidler-Mckay, John V Heymach, Lauren A Byers, Faye M Johnson, Vlad C Sandulache, Jeffrey N Myers, Pedram Yadollahi, Mitchell J Frederick

Faculty, Staff and Students Publications

Inactivating NOTCH1 mutations in head and neck squamous cell carcinoma (HNSCC) were described over a decade ago, suggesting a tumor suppressor function - unlike its oncogenic role in other tumors. Today, much debate persists regarding a putative oncogenic role in HNSCC as well, with reports that NOTCH1 signaling drives tumor growth and a cancer stem cell (CSC) phenotype. In this work, comprehensive experiments unequivocally demonstrate that NOTCH1 is a tumor suppressor in HNSCC regardless of mutation or activation status and that it reduces CSC frequency. We developed a signature of NOTCH1 activation showing the pathway is associated with very early …

Monoclonal Antibodies Targeting Pcdh7 Inhibit Tumor Growth And Enhance Immune Responses In Kras-Mutant Non-Small Cell Lung Cancer, Nicole Novaresi, Poorva Ghosh, Shayna Thomas-Jardin, Hui Deng, Xuejun Fan, Zhiqiang Ku, Wei Xiong, Xiaorong Zhou, Jingfei Zhu, Huiyu Li, Mahesh S Padanad, Bethany Smith, Chul Ahn, John D Minna, Zhiqiang An, Ningyan Zhang, Kathryn A O'Donnell

The Brown Foundation: Institute of Molecular Medicine

We identified an important oncogenic role for protocadherin 7 (PCDH7), a cell surface protein frequently overexpressed in lung adenocarcinoma and associated with poor clinical outcome. Pcdh7 depletion reduces tumor burden and prolongs survival in KrasLSL-G12D; Tp53fl/fl mice. These findings nominate this cell surface protein as an actionable therapeutic target and highlight the therapeutic potential of PCDH7 inhibition for non–small cell lung cancer. We report the development and characterization of high-affinity anti-PCDH7 monoclonal antibodies (mAbs) that inhibit downstream mitogen-activated protein kinase (MAPK) pathway activation and suppress tumor growth in multiple mutant KRAS–driven models. A lead mAb (mAb7) sensitized tumors …

Amc-F1 Regulates Mitochondria-Autophagy Crosstalk Independent Of Nutrient Stress, Yuqin Wang, Raksha K Rao, Trung Vu, Ayano Sekine, Zhengmei Mao, Nami Mccarty

The Brown Foundation: Institute of Molecular Medicine

Mitochondria and autophagy are fundamental yet distinct regulators of cellular homeostasis. Here, we identify AMC-F1 (Autophagy-Mitochondria Coupling Factor 1; formerly TRIM44) as a central integrator of mitochondrial bioenergetics and autophagy. Using Amcf1 knockout and knock-in mouse models, we demonstrate that AMC-F1 bidirectionally regulates these pathways: its loss reduces mitochondrial respiration and autophagic flux, whereas its overexpression promotes mitochondrial elongation and increases autophagy independently of nutrient stress. Transcriptomic analyses reveal AMC-F1-dependent regulation of mitochondrial biogenesis programs that engage autophagy, involving mitochondrial respiratory chain complex genes under basal conditions and mitochondrial organization factors under starvation-induced autophagy. Although dispensable under homeostasis, this coupling …

Histone Deacetylase Enzyme Activity Is Not The Universal Anticancer Target Of Hdac Inhibitors, Chaitra Rai, Hang Ruan, Xue Li, Wenbo Li, Hyun-Hwan Jeong, Chengchuang Song, Panpan Liu, Yingjie Chang, Hao Fang, Udhaya Kumar S, Yuxiang Sun, M James You, Dongyin Guan, Zhandong Liu, Leng Han, Xuben Hou, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase inhibitors (HDIs) are approved for treating hematologic cancers and are currently being evaluated in hundreds of clinical trials for various cancers and other diseases, although their mechanisms of action remain poorly understood. Here, our unbiased bioinformatics analyses found that, for most cancer types, expression levels or genetic variants of histone deacetylase (HDACs) do not consistently correlate with carcinogenesis, do not predict cancer patient survival, and do not associate with cellular responses to HDIs. Whole-genome CRISPR library screens did not identify HDACs as genes affecting cellular responses to HDIs. Overexpression of dominant-negative Class I HDACs causes similar protein hyperacetylation …

Transgenic Hookworm Secretes Anti-Tetrodotoxin Human Single Chain Antibody, Kumar Sachin Singh, Suman Bharti, Bruce A Rosa, Mahdiyeh Bigham, Samuel C Uzoechi, Young-Jun Choi, John C Martin, Danielle Kemper, Slavica Pavlovic Djuranovic, Darren A Pickering, Rachael Ryan, Bethany K Bracken, Maria Elena Bottazzi, Eric C Carnes, Wannaporn Ittiprasert, Matthew Moyle, Paul J Brindley, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva

Faculty, Staff and Students Publications

Biologics, protein- and peptide-based drugs derived from living organisms or cell lines have emerged as effective therapies across a broad range of indications. However, parenteral administration and the need for frequent dosing increase costs and limit compliance, creating an urgent need for innovative platforms capable of continuously, safely, and efficiently delivering sustained biologics in situ within the host. Here, we describe a bioengineered hookworm platform to manufacture and deliver biologic therapeutics in vivo. As proof of concept, we engineer the Ancylostoma ceylanicum secretome by inserting a human single-chain variable fragment antibody (s16-HuScFv) into its genome. Transgene expression does not perturb …

Complement Activation In Maternal And Placental Pathology Of Preeclampsia, Manu T Banadakoppa, Madhulatha S Chauhan, Moises J Tacam, Allyson W Nevins, Antonio H Ruano, Simone H Ruano, Jon A Fuson, Chandra Yallampalli

Faculty, Staff and Students Publications

Background: Preeclampsia is a multifactorial, pregnancy-related disorder characterized by new-onset hypertension and proteinuria, with distinct early- and late-onset forms. Although complement dysregulation has been implicated in the pathogenesis of preeclampsia, its causal role remains unclear. In mice, Crry (complement receptor 1-related protein Y) functions as a critical complement regulator at the fetal-maternal interface. Because complete Crry deficiency is embryonically lethal, direct in vivo investigation of complement activation in pregnancy has been challenging.

Methods: We generated a placenta-specific, doxycycline-inducible short hairpin RNA mouse model in which Crry expression can be downregulated in a dose-dependent manner. This system employs Cyp19-driven Cre recombinase …

Cytosine Base Editing Of Lpa In Transgenic Mice Averts Large Deletions, Marcel A Chuecos, So Hyun Park, Madhvi M Bhakta, Usosa Too-Chiobi, Daniel Betancourth, Mingming Cao, Marco De Giorgi, Christopher J Walkey, Anjana Tiwari, Biana Godin, Julia M Assini, Donna J Palmer, Philip Ng, Michael B Boffa, Marlys L Koschinsky, Gang Bao, William R Lagor

Faculty, Staff and Students Publications

Lipoprotein(a) (Lp(a)) is a genetically determined causal risk factor for cardiovascular disease, with approximately 20% of the population exhibiting elevated levels. While there are promising drugs in development, there are currently no approved therapies specifically designed to lower Lp(a) levels. For high-risk individuals with extreme levels of Lp(a), liver-directed genome editing could be an effective one-time solution. Genome editing approaches such as CRISPR and TALENs can reduce Lp(a) in LPA-transgenic mouse models, but they frequently induce large and potentially harmful genomic deletions. Here, we report the first application of TadA-derived cytosine base editing (CBE), delivered via helper-dependent adenovirus (HDAdV) and …

Molecular And Histologic Studies Of The Amygdala And Reward Circuits In Rhesus Macaques (Macaca Mulatta) With Self-Injurious Behavior (Sib), Jackie Barua

Doctoral Dissertations

Self-injurious behavior (SIB), also known as non-suicidal self-injury (NSSI), is characterized by deliberate infliction of harming one’s own body tissues without committing suicide, and persists in a group of captive rhesus macaques despite an enhanced enrichment program and pharmacological intervention with diazepam. The aim of this dissertation was to identify the neurobiological underpinnings of SIB by combining RNA-seq guided transcriptomic discovery and targeted candidate gene validation with unbiased histological and imaging analysis. The secondary aim was to employ a complementary mouse model to investigate the endogenous opioid system in response to diazepam. The amygdala transcriptome of primates with SIB (n …

Activated Dorsomedial Hypothalamic Astrocytes Regulate Feeding Behavior, Bella M. Lisenby

Honors Projects

The dorsomedial hypothalamus (DMH) region of the brain has been shown to be important for anticipatory feeding activity and play a role in restricting excessive food intake. In obese animals that overconsume calories, astrocytes within the DMH exhibit intracellular signaling changes indicative of cellular activation. Because astrocytes are known to influence neuronal function, we hypothesize that activated astrocytes regulate behavior. In the current study, we use chemogenetics combined with stereotaxic surgery to assess the contribution of astrocyte activity in the DMH towards metabolic behaviors.

Fentanyl Mediated Distortions Of Phasic Dopamine Release Dynamics Encoding Natural Reward And Aversive Processing In The Mammalian Mesolimbic Circuit, Oliver P. Culver Iv

MUSC Theses and Dissertations

Mu opioid receptor (MOR) agonists are recognized to disinhibit tonic dopamine (DA) in the ventral striatum (VS), contributing to opioid addiction and euphoria. However, MOR agonists can also inhibit non-drug reward-seeking, and disrupt conditioned responding to aversive stimuli, a phenomenon not readily explained by tonic DA disinhibition. We hypothesized that this effect could be due in part to disruption of phasic DA responses to conditioned stimuli (CS) which critically shape and maintain behaviors during naturalistic reward and aversive processing. Because MOR effects on CS-evoked phasic DA are largely unexamined, we conducted in vivo fiber photometric recordings in water-deprived male and …

Nmda Receptor Subunit Nmr-2 Regulates Pathogen-Induced Immune Responses Via The Nervous System In C. Elegans, Benson Otarigho, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

Neural control of innate immunity must balance restraint of basal immune activity with rapid activation upon pathogen encounter. Glutamate, the primary excitatory neurotransmitter in the nervous system, has been implicated in several neurological disorders associated with inflammation, suggesting a potential link to immune regulation. However, how glutamatergic signaling contributes to immune balance remains unknown. Here, we demonstrated that the NMDA-type ionotropic glutamate receptor subunit NMR-2, a component of the NMDA receptor complex, acts in the

Reducing Cardiovascular Disease Risk In Obesity: An Unexpected But Welcome Fourier Transformation, Layla A Abushamat, Arsalan Hamid, Vijay Nambi, Huaizhu Wu, Christie M Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

Calcium Signaling And Postsynaptic Density Dynamics: The Roles Of Calmodulin In Synaptic Protein Regulation, Keyaa Dilip Shah, Yonghong Zhang

School of Integrative Biological & Chemical Sciences Faculty Publications

Calcium signaling in neuronal cells is the principal mechanism underlying learning and synaptic plasticity, whereas the postsynaptic density (PSD) is an important center where calcium-dependent processes are organized and regulated. This review explores the roles of calmodulin (CaM) in facilitating calcium-dependent modulation of the activities of synaptic proteins in the PSD. We focus on the molecular processes through which CaM interacts with calcium signals to regulate the function, localization, and interactions of central synaptic proteins, including calcium/calmodulin-dependent protein kinase II (CaMKII), membrane-associated guanylate kinases (MAGUKs), and N-methyl-D-aspartate (NMDA) receptors. We aim to summarize recent advances in structural, biochemical, and imaging …

Neuroinflammation And Neuropathology In A Novel Tau, Amyloid-Beta And Alpha-Synuclein Co-Pathology Model, Jhodi Mickayla Webster

ETDs from 2020-2029

Neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson disease (PD) often present with overlapping proteinopathies rather than aggregated proteins in isolation. Amyloid-β (Aβ) and phosphorylated tau are found in a substantial proportion of idiopathic PD cases, while α-synuclein (α-syn) pathology is present in over half of AD cases. The presence of these co-pathologies is associated with accelerated cognitive decline and increase mortality in these patients. In parallel, neurodegenerative diseases are increasingly recognized as being shaped by interactions between central nervous system (CNS) pathology and the immune system. Despite this, most experimental animal models of neurodegenerative disease examine single pathologies in …

An Obligatory Role For Agrp Neurons In Maintaining Body Temperature During Time-Restricted Feeding, Cunjin Su, Jing Cai, Yuanzhong Xu, Benjamin R Arenkiel, Qingchun Tong

The Brown Foundation: Institute of Molecular Medicine

Homeotherms maintain a steady body temperature through thermoregulation, a process critical for survival during fasting, in which the brain has to defend energy-costly body temperature while reducing energy expenditure to conserve energy reserve; however, the neural basis for defending body temperature remains unclear. Here, we demonstrated that AgRP neuron lesion led to lethality during time-restricted feeding on chow but not on HFD, and caused no obvious impact on HFD-induced obesity or obesity-reducing responses to glucagon-like peptide-1 receptor agonism. The lesion disrupted adaptive feeding behaviors during time-restricted feeding and reduced motivational feeding on chow. Notably, the lethality was caused by hypothermia …