Digital Commons Network^™

Gene Expression Changes In Human Cerebral Arteries Following Hemoglobin Exposure: Implications For Vascular Responses In Sah, Chathathayil M Shafeeque, Arif O Harmanci, Sithara Thomas, Ari C Dienel, Devin W Mcbride, Kumar T Peeyush, Spiros L Blackburn

Faculty, Staff and Student Publications

Subarachnoid hemorrhage (SAH), characterized by the presence of hemoglobin (Hb) in the subarachnoid space, significantly impacts cerebral vessels, leading to various pathological outcomes. The toxicity of cell-free Hb released from erythrocytes and its metabolites after SAH causes vasoconstriction and neuronal damage, and correlates with delayed ischemic neurological deficits (DIND). While animal models have provided substantial and invaluable data in the research of aneurysmal SAH, the specific effects of subarachnoid blood on cerebral arteries remain greatly understudied. Here, we describe the changes in the genetic profile of human cerebral arteries exposed to free Hb for 48 h. We performed an ex …

A Decision-Space Model Explains Context-Specific Decision Making, Dirk W. Beck, Cory N. Heaton, Luis D. Davila, Lara I. Rakocevic, Sabrina M. Drammis, Danil Tyulmankov, Atanu Giri, Shreeya Umashankar Beck, Qingyang Zhang, Michael Pokojovy, Kenichiro Negishi, Alexis A. Salcido, Neftali F. Reyes, Andrea Y. Macias, Serina A. Batson, Paulina Vara, Raquel J. Ibáñez Alcalá, Safa B. Hossain, Graham L. Waller, Laura E. O'Dell, Travis M. Moschak, Ki A. Goosens, Alexander Friedman

Mathematics & Statistics Faculty Publications

Optimal decision-making requires consideration of internal and external contexts. Biased decision-making is a transdiagnostic symptom of neuropsychiatric disorders. We created a computational model demonstrating how the striosome compartment of the striatum constructs a context-dependent mathematical space for decision-making computations, and how the matrix compartment uses this space to define action value. The model explains multiple experimental results and unifies other theories like reward prediction error, roles of the direct versus indirect pathways, and roles of the striosome versus matrix, under one framework. We also found, through new analyses, that striosome and matrix neurons increase their synchrony during difficult tasks, caused …

The Management Of Dietary Fiber Intake In Children With Chronic Kidney Disease - Clinical Practice Recommendations From The Pediatric Renal Nutrition Taskforce., An Desloovere, Nonnie Polderman, José Renken-Terhaerdt, Vanessa Shaw, Caroline Anderson, Larry A. Greenbaum, Christina L. Nelms, Leila Qizalbash, Stella Stabouli, Jetta Tuokkola, Bradley A. Warady, Johan Vande Walle, Fabio Paglialonga, Rukshana Shroff, Evelien Snauwaert

Manuscripts, Articles, Book Chapters and Other Papers

The benefits of dietary fiber are widely accepted. Nevertheless, a substantial proportion of children fail to meet the recommended intake of dietary fiber. Achieving adequate fiber intake is especially challenging in children with chronic kidney disease (CKD). An international team of pediatric renal dietitians and pediatric nephrologists from the Pediatric Renal Nutrition Taskforce (PRNT) has developed clinical practice recommendations (CPRs) for the dietary intake of fiber in children and adolescents with CKD. In this CPR paper, we propose a definition of fiber, provide advice on the requirements and assessment of fiber intake, and offer practical guidance on optimizing dietary fiber …

Integrating Human And Animal Health In The Stop Spillover Outbreak Scenarios, Kathleen E. Angell, He Julia Bai, Katherine C. Prager, Janetrix H. Amuguni, Felicia B. Nutter, Jonathan D. Gass Jr, David Brett-Major

Journal Articles: Epidemiology

OBJECTIVES: To generate and employ scenarios of sentinel human and animal outbreak cases in local contexts that integrate human and animal health interests and practices and facilitate outbreak risk management readiness.

METHODS: We conducted a scoping review of past outbreaks and the strengths and weaknesses of response efforts in USAID STOP Spillover program countries. This information and iterative query-and-response with country teams and local stakeholders led to curated outbreak scenarios emphasizing One Health human:animal interfaces at sub-national levels.

RESULTS: Two core scenarios were generated adapted to each of 4 countries’ pathogen priorities and workflows in Africa and Asia, anchoring on …

Development Of 2d Microfluidics Surface With Low-Frequency Electric Fields For Cell Separation Applications, Madushan Wickramasinghe, Dharmakeerthi Nawarathna

Electrical & Computer Engineering Faculty Publications

Cell separation techniques are widely used in many biomedical and clinical applications for the development of screening, diagnosis and therapeutic tests. Current 3D microfluidics-based cell separation methods have limited applications in part due to low throughput and technical complexity. To address these critical needs, we have developed a 2D microfluidics surface which is the miniaturized version of a 3D microfluids cell separation device. Using low-frequency electric fields (1–10 Vpp and 1 kHz–20 MHz), we have first studied dielectrophoresis, AC electro-osmosis and capillary flow within a sessile drop, and finally utilized the results to develop the 2D cell separation surface. Our …

Microglial Trem2 Promotes Phagocytic Clearance Of Damaged Neurons After Status Epilepticus, Dale B Bosco, Vaclav Kremen, Koichiro Haruwaka, Shunyi Zhao, Lingxiao Wang, Blake A Ebner, Jiaying Zheng, Manling Xie, Aastha Dheer, Jadyn F Perry, Abhijeet Barath, Aivi T Nguyen, Gregory A Worrell, Long-Jun Wu

The Brown Foundation: Institute of Molecular Medicine

In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. Microglial TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about how TREM2 affects microglial function within epileptogenesis. To investigate this, we utilized male TREM2 knockout (KO) mice within the intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both the severity of acute status epilepticus …

Match Accuracy Of Burned Teeth: A Pilot Study Of Allied Dental Professionals, Brenda T. Bradshaw, Marsha A. Voelker, Samantha C. Vest, Sinjini Sikdar

Dental Hygiene Faculty Publications

Purpose: The purpose of this pilot study was to assess allied dental professionals' match accuracy of burned teeth; a skill required by disaster victim identification (DVI) team members.

Methods: This cross-sectional study used a convenience sample of registered dental hygienists (RDH) (n=15) and dental assistants (DA) (n=15) to assess their match accuracy of burned teeth with simulated antemortem (AM) and postmortem (PM) images. Fifteen human teeth were heated at 400°C for 15 minutes. Prior to and following heat alteration, each tooth was photographed and radiographed. Images were presented to participants in randomized order, and they were instructed to correctly match …

Depletion Of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy, Joseph Rupert, Alexes Daquinag, Yongmei Yu, Yulin Dai, Zhongming Zhao, Mikhail G Kolonin

Faculty, Staff and Student Publications

This study shows that populations of CAFs have distinct effects on pancreatic cancer progression and shows that depletion of CAFs expressing adipose markers potentiates tumor/metastasis suppression effects of immune checkpoint blockade.

Tourette Syndrome Research Highlights From 2024 [Version 3; Peer Review: 2 Approved, 1 Approved With Reservations], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Simon Morand-Beaulieu, Nanette Mol Debes, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

We summarize research reports from 2024 relevant to Tourette syndrome, which the authors consider the most important or interesting. This working draft aims to submit this content for publication around the beginning of 2025 in the yearly Tourette Syndrome Research Highlights series on F1000Research. The authors welcome article suggestions and thoughtful feedback from readers, who can add a comment by clicking on the rectangular comment box icon to the left of the LOG IN link at the top of this page. For private comments, you can reach us by email ( [email protected] or [email protected]).

Slc35a2 Gene Product Modulates Paramyxovirus Fusion Events During Infection, Yanling Yang, Yuchen Wang, Danielle E. Campbell, Heng-Wei Lee, Wandy Beatty, Leran Wang, Megan Baldridge, Carolina B. López

2020-Current year OA Pubs

Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection. As expected, SLC35A1 knockout (KO) cells showed drastic reduction in infections with SeV, NDV and MuV due to the lack of cell surface sialic acids receptors. However, SLC35A2 KO cells revealed …

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

Contract To Kill: Gnas Mutation, Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

The mutation in Gsα-coding GNAS exons, popular as gsp oncogene, is the most frequent mutation across all heterotrimeric G proteins involved in oncogenesis. GNAS R201, the most frequently mutated, followed by Q227, are found predominantly across various neoplasms and cancers such as IPMN, pituitary, thyroid, appendiceal, colorectal, etc. This review emphasizes the pivotal significance of the gsp oncogene and its ramifications underpinning the sustained addiction to GNAS mutation. Recent studies delineating the mechanistic intricacies that provide solid evidence of the profound impact of oncogenic GNAS on tumor formation, progression, and maintenance are highlighted. We have leveraged the discoveries of Gsα …

Revisiting Icd Therapy For Primary Prevention In Patients With Heart Failure And Reduced Ejection Fraction., Amin Yehya, Jose L Batista, Andrew J Sauer, Jonathan D Davis, Nasrien E Ibrahim, Roderick Tung, Biykem Bozkurt, Gregg C Fonarow, Sana M Al-Khatib

Faculty, Staff and Students Publications

Implantable cardioverter-defibrillators (ICDs) are recommended to reduce the risk of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF). The landmark studies leading to the current guideline recommendations preceded the 4 pillars of guideline-directed medical therapies (GDMTs). Therefore, some have questioned the role of ICDs for primary prevention in current clinical practice. In this paper, the authors provide an overview of the current ICD recommendations, including the instrumental clinical trials, the risk of SCD as observed in clinical trials vs real-world scenarios, disparities in ICD use among different patient populations, the impact of contemporary GDMT …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Biallelic Variation In The Choline And Ethanolamine Transporter Flvcr1 Underlies A Severe Developmental Disorder Spectrum, Daniel G Calame, Jovi Huixin Wong, Puravi Panda, Dat Tuan Nguyen, Nancy C P Leong, Riccardo Sangermano, Sohil G Patankar, Mohamed S Abdel-Hamid, Lama Alabdi, Sylvia Safwat, Kyle P Flannery, Zain Dardas, Jawid M Fatih, Chaya Murali, Varun Kannan, Timothy E Lotze, Isabella Herman, Farah Ammouri, Brianna Rezich, Stephanie Efthymiou, Shahryar Alavi, David Murphy, Zahra Firoozfar, Mahya Ebrahimi Nasab, Amir Bahreini, Majid Ghasemi, Nourelhoda A Haridy, Hamid Reza Goldouzi, Fatemeh Eghbal, Ehsan Ghayoor Karimiani, Amber Begtrup, Houda Elloumi, Varunvenkat M Srinivasan, Vykuntaraju K Gowda, Haowei Du, Shalini N Jhangiani, Zeynep Coban-Akdemir, Dana Marafi, Lance Rodan, Sedat Isikay, Jill A Rosenfeld, Subhadra Ramanathan, Michael Staton, Kerby C Oberg, Robin D Clark, Catharina Wenman, Sam Loughlin, Ramy Saad, Tazeen Ashraf, Alison Male, Shereen Tadros, Reza Boostani, Ghada M H Abdel-Salam, Maha Zaki, Ali Mardi, Farzad Hashemi-Gorji, Ebtesam Abdalla, M Chiara Manzini, Davut Pehlivan, Jennifer E Posey, Richard A Gibbs, Henry Houlden, Fowzan S Alkuraya, Kinga Bujakowska, Reza Maroofian, James R Lupski, Long N Nguyen

Faculty, Staff and Students Publications

Purpose: FLVCR1 encodes a solute carrier protein implicated in heme, choline, and ethanolamine transport. Although Flvcr1-/- mice exhibit skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia (DBA), biallelic FLVCR1 variants in humans have previously only been linked to childhood or adult-onset ataxia, sensory neuropathy, and retinitis pigmentosa.

Methods: We identified individuals with undiagnosed neurodevelopmental disorders and biallelic FLVCR1 variants through international data sharing and characterized the functional consequences of their FLVCR1 variants.

Results: We ascertained 30 patients from 23 unrelated families with biallelic FLVCR1 variants and characterized a novel FLVCR1-related phenotype: severe developmental disorders with profound developmental delay, microcephaly …

Cancer-Targeted Pro-Theranostic Bi-Metallic Organo-Coordination Nanoparticles, Hengbo Huang, Lei Fang, Janaka Wansapura, Julie L Prior, Brad Manion, Baogang Xu, Cody Hongsermeier, Nisha Gamadia, Nicole Blasi, Rui Tang, Christopher Egbulefu, Monica Shokeen, James D Quirk, Samuel Achilefu

2020-Current year OA Pubs

No abstract provided.

Edible Algae Reduce Blood Pressure In Humans: A Systematic Review And Meta-Analysis Of Randomised Controlled Trials, Patricia Casas-Agustench, Sandra Mínguez, Zoe Brookes, Raul Bescos

School of Health Professions

BACKGROUND: Edible algae contain bioactive compounds such as peptides, fucoidan, polyphenols, potassium, omega-3 fatty acids, and antioxidants that may benefit cardiovascular health, particularly in lowering blood pressure (BP) regulation. Certain species, including Nori and Kelp, are also rich in inorganic nitrate, known for its BP-lowering effects. However, the relationship between algae consumption and hypertension remains controversial. This study evaluated the effects of edible algae on BP in humans, considering factors such as algae type, format, dosage, intervention duration, health status, and baseline BP.

METHODS: A systematic search of Medline-Pubmed, Scopus and Cochrane databases was conducted through December 2024. Randomised controlled …

Clinical Significance Of "S" Isoform Of Dclk1 In Different Gastric Cancer Subtypes Using Newly Produced Monoclonal Antibody, Mahdieh Razmi, Ali-Ahmad Bayat, Nafiseh Mortazavi, Elham Kalantari, Leili Saeednejad Zanjani, Sima Saki, Roya Ghods, Zahra Madjd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Materials and methods

Cooperative Role Of Distinctive Tp53 And Pten Combined Loss In The Peripheral T Cell Lymphoma-Gata3 Molecular Subgroup, Waseem G. Lone, Jiayu Yu, Xuxiang Liu, Dylan T. Jochum, Alyssa Bouska, Kunal Shetty, Tyler Herek, Sunandini Sharma, Chengfeng Bi, Rauf Shah, Zaina W. Nasser, Catalina Amador, Aiza Arif, Abdul Rouf Mir, Yuping Li, Tayla B. Heavican-Foral, Jacob Robinson, R. Katherine Hyde, Mamiko Sakata-Yanagimoto, Satyanarayana Rachagani, Timothy W. Mckeithan, David W. Scott, Louis M. Staudt, Giorgio Inghirami, Andrew Feldman, Timothy Greiner, Julie M. Vose, Lisa Rimsza, Joseph Khoury, Wing C. Chan, Javeed Iqbal, Lymphoma/Leukemia Molecular Profiling Project (Llmpp)

Journal Articles: Oncology and Hematology

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of postthymic T cell neoplasms, with ~40% classified as PTCL-not otherwise specified (PTCL-NOS). PTCL-GATA3, a molecularly defined subtype, associated with T helper 2 (T_H2)-like differentiation and poor prognosis, has frequent co-occurrence of TP53 loss/mutation and heterozygous PTEN loss. CD4+ T cell conditional mouse models with Trp53 mutation/deletion and Pten loss demonstrated mature T cell lymphomas (mTCLs) with T_H2-like transcriptomic and immunophenotypic profiles. Molecular studies revealed that codeletion of Trp53/Pten induced T cell receptor and Janus kinase-signal transducer and activator of transcription signaling, promoting T_H2 differentiation …

A Comprehensive Review On Utilizing Human Brain Organoids To Study Neuroinflammation In Neurological Disorders, Adrian Domene Rubio, Luke Hamilton, Mark Bausch, Mengmeng Jin, Ava Papetti, Peng Jiang, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Most current information about neurological disorders and diseases is derived from direct patient and animal studies. However, patient studies in many cases do not allow replication of the early stages of the disease and, therefore, offer limited opportunities to understand disease progression. On the other hand, although the use of animal models allows us to study the mechanisms of the disease, they present significant limitations in developing drugs for humans. Recently, 3D-cultured in vitro models derived from human pluripotent stem cells have surfaced as a promising system. They offer the potential to connect findings from patient studies with those from …

Proteomics Profiling Of Research Models For Studying Pancreatic Ductal Adenocarcinoma, Mathilde Resell, Hanne-Line Rabben, Animesh Sharma, Lars Hagen, Linh Hoang, Nan T. Skogaker, Anne Aarvik, Eirik Knudsen Bjåstad, Magnus K. Svensson, Manoj Amrutkar, Caroline S. Verbeke, Surinder K. Batra, Gunnar Qvigstad, Timothy C. Wang, Anil Rustgi, Duan Chen, Chun-Mei Zhao

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a five-year survival rate of 10-15% due to late-stage diagnosis and limited efficacy of existing treatments. This study utilized proteomics-based systems modelling to generate multimodal datasets from various research models, including PDAC cells, spheroids, organoids, and tissues derived from murine and human samples. Identical mass spectrometry-based proteomics was applied across the different models. The preparation and validation of the research models and the proteomics were described in detail. The assembly datasets we present here contribute to the data collection on PDAC, which will be useful for systems modelling, …

Diastolic Dysfunction With Vascular Deficits In Hiv-1-Infected Female Humanized Mice Treated With Antiretroviral Drugs, Fadhel A. Alomar, Prasanta K. Dash, Mahendran Ramasamy, Zachary L. Venn, Sean R. Bidasee, Chen Zhang, Bryan T. Hackfort, Santhi Gorantla, Keshore R. Bidasee

Journal Articles: Cellular & Integrative Physiology

Early-onset heart failure is a major treat to healthy aging individuals with HIV-1 infection. Women with HIV-1 infection (WLWH) are especially vulnerable and develop heart failure with preserved ejection fraction (HFpEF), of which left ventricular diastolic dysfunction, vascular deficits, myocardial infarction, and fibrosis are major components. HIV-infected rodent models that exhibit these pathophysiological features remain under-reported, and this has left a void in our understanding of their molecular causes and therapeutic strategies to blunt its development. Here, we show that female NOD.Cg-Prkdc^scidIl2rgt^m1Wjl/SzJ humanized mice (Hu-mice) infected with HIV-1_ADA and treated for 13 weeks with dolutegravir …

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 …

Pregnancy Outcomes After Exposure To Tuberculosis Treatment In Phase 3 Clinical Trial, 2016-2020, Ekaterina V. Kurbatova, William C. Whitworth, Kia E. Bryant, Meredith G. Dixon, Kelly E. Dooley, Nigel A. Scott, Rosanna Boyd, Nicole E. Brown, Kimberley N. Chapman Hedges, Wendy Carr, Lakshmi P. Peddareddy, Grace Muzanyi, Rodney Dawson, Ziyad Waja, Neil Martinson, Jyoti S. V. Mathad, Payam Nahid, Susan Swindells, Richard E. Chaisson, Susan E. Dorman, Patrick P. J. Phillips, Aids Clinical Trials Group A5349, Tuberculosis Trials Consortium Study 31

Journal Articles: Infectious Diseases

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We analyzed pregnancy outcomes of women who became pregnant during the study. Among 740 women, 97 (13.1%) became pregnant. Of 102 pregnancies (in 97 participants), 30 (29.4%) participants were exposed to study drugs. Fetal loss was reported for 3/13 (23.1%) in the control regimen, 1/9 (11.1%) in the rifapentine/moxifloxacin regimen, and 1/8 (12.5%) in the rifapentine regimen. Among 21 live births in exposed pregnancies (7 in each arm), 1 infant with a congenital anomaly was reported in a participant on the …

Lactate's Role In Appetite Suppression, Seth Mccarthy

Theses and Dissertations (Comprehensive)

Once considered metabolic waste produced during exercise, lactate is now known to have diverse roles in biology. Muscle-derived lactate can travel through the bloodstream and be taken up by other tissues and i) oxidized, ii) converted to glucose via gluconeogenesis, or iii) bind to its receptor to trigger molecular signaling cascades. Lactate has been described as a “myokine” capable of inter-organ crosstalk and compelling evidence demonstrates lactate’s role as a signalling molecule in pathways related to the regulation of appetite. The purpose of this dissertation was to further elucidate lactate’s role in appetite regulation using series of studies aimed at …

Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici

Faculty, Staff and Students Publications

Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …

A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhidan Zhang, Meijie Chen, Yitong Xu, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu

Faculty, Staff and Students Publications

Rationale: Atherosclerotic cardiovascular disease (ASCVD) represents the predominant cause of mortality and morbidity globally. Given the established role of hypercholesterolemia as a significant risk factor for ASCVD, the discovery of new lipid-lowering medications is of paramount importance. ATP citrate lyase (ACLY) is a crucial enzyme in cellular metabolism, providing acetyl-CoA as the building block for the biosynthesis of fatty acids and cholesterol. Consequently, it has emerged as a promising drug target for innovative treatments of lipid metabolic disorders.

Methods: Virtual screening of a natural product library was performed to identify small-molecule ACLY inhibitors, leading to the discovery of isoginkgetin (ISOGK). …

Syndromic Forms Of Inherited Retinal Dystrophies: A Comprehensive Molecular Diagnosis Of Consanguineous Pakistani Families Using Capture Panel Sequencing, Aleesha Asghar, Sumbal Wazir, Shehzeen Fatima, Hussan Bilal, Muhammad Shoaib, Saqib Ur Rehman, Sumaira Altaf, Yumei Li, Kiran Afshan, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Background: Inherited retinal dystrophies (IRDs) represent a clinically and genetically heterogeneous group of genetic disorders that involve photoreceptors and/or retinal pigment epithelium degeneration. IRDs may occur as an isolated condition or may represent an ocular manifestation of a multisystemic disorder referred as syndromic IRD. To increase the understanding of the molecular determinants of syndromic IRD-related genes in the Pakistani population, we revealed the genetic profile of 13 consanguineous Pakistani families using capture panel sequencing.

Methods: We performed comprehensive molecular testing on 72 IRD segregating Pakistani families using targeted capture panel sequencing of 344 known genes. The pathogenicity of candidate variants …

The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza

Faculty, Staff and Students Publications

The Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger transcription factor that regulates cellular processes in stem cells, epithelial cells, and immune blood cells by controlling gene expression through genetic, epigenetic, and chromatin remodeling. The landmark 2006 publication identified KLF4 as one of the factors involved in reprogramming differentiated cells into pluripotent stem cells, sparking increased interest in KLF4 research a decade after its discovery, particularly in the fields of stem cell research, epithelial cell biology, endothelial cell function, and tumorigenesis. Over the years, KLF4 has emerged as a key transcription factor in modulating innate and adaptive immunity, …

Poststroke Impulsivity: A Narrative Review, Melissa B Jones, Dakota E Broadway, Malena Gimenez-Zapiola, Ricardo E Jorge

Faculty, Staff and Students Publications

In this narrative review, the authors examine the multidimensional nature and presentations of impulsivity after stroke. Impulsivity manifests as immediate or premature responses, impaired delayed gratification, perseverance despite punishment, and other displays of impaired emotional and behavioral regulation. The literature on the assessments, outcomes, and treatment of patients with these various manifestations after a cerebrovascular injury is reviewed. Findings from case reports indicate that poststroke impulsivity may manifest across neurobehavioral syndromes that are not well defined in the psychiatric nomenclature, such as alien hand syndrome and atypical impulse control disorders. Overall, impulse control disorders appear to be rare poststroke. Therapeutic …