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Full-Text Articles in Entire DC Network
Evaluation Of Tick-Derived Peptides For Transmission-Blocking Vaccine Candidates, Madelyn Futral
Evaluation Of Tick-Derived Peptides For Transmission-Blocking Vaccine Candidates, Madelyn Futral
Honors Theses
The lack of effective preventive measures for tick-borne diseases represents a major public health challenge. Transmission-blocking vaccines targeting tick molecules essential for feeding or reproduction could provide a sustainable and broad-spectrum solution. In this study, we evaluated two tick-derived proteins as potential vaccine antigens, subolesin, a key regulator of blood-feeding and cellular processes, and vitellogenin, a protein involved in egg development. Using bioinformatic tools, we identified immunogenic peptide sequences from each protein and chemically conjugated them to virus-like particles (VLPs) to enhance antigen presentation. C57BL/6 mice were immunized intradermally with VLP-peptide conjugates, followed by a booster dose. Blood and spleen …
Effects Of Kiwifruit Extract On Apoptosis And Cytokine Production In Inflamed Thp-1-Derived Macrophages, Adrian Cruz, Isbella Brigman
Effects Of Kiwifruit Extract On Apoptosis And Cytokine Production In Inflamed Thp-1-Derived Macrophages, Adrian Cruz, Isbella Brigman
Posters - 2026
White blood cells are essential components of the immune system involved in helping defend the body against infections. Macrophages are a type of white blood cell that play a major role in stimulating and regulating the inflammatory response. Inflammation is a natural response of the immune system to infection, injury, or harmful stimuli. Scientific research commonly studies inflammation by exposing immune cells to lipopolysaccharide (LPS). Macrophages stimulated with LPS undergo changes in cell processes such as apoptosis which is programmed cell death. Apoptosis is crucial for the immune system that helps eliminate infected or damaged cells to prevent the spread …
The Effects Of Mycoplasma Pneumoniae Cards Toxin On M2 Macrophage Polarization And Formation, Ria Modi
The Effects Of Mycoplasma Pneumoniae Cards Toxin On M2 Macrophage Polarization And Formation, Ria Modi
Posters - 2026
Macrophages are key cells of the innate immune system, playing essential roles in host defense, tissue homeostasis, and inflammation. Depending on stimuli, macrophages can polarize into distinct functional phenotypes, characterized as classically activated (M1) or alternatively activated (M2) macrophages. M2 macrophages are associated specifically with anti-inflammatory responses, tissue repair, and immune regulation. They contribute to wound healing and can regulate host responses during infection. Community-acquired respiratory distress syndrome (CARDS) toxin, a key virulence factor of Mycoplasma pneumoniae, plays a role in altering host immune responses, but its impact on M2 macrophage function and polarization remains unclear.
Role Of Listeria Adhesion Protein In Monocyte-Associated And Extracellular Translocation Of Listeria Monocytogenes Across The In Vitro Placental Barrier Co-Culture Model, Ayesha Atique
Biological Sciences Theses & Dissertations
Listeria monocytogenes is a facultative intracellular foodborne pathogen capable of crossing the placental barrier, leading to miscarriage, stillbirth, and neonatal sepsis, and has a fetal/neonatal fatality rate of ~20–30%. Although the importance of canonical virulence factors such as Internalin A (InlA) and Internalin B (InlB) in L. monocytogenes crossing of the placental barrier has been demonstrated, clinical strains lacking functional canonical internalins have been reported to cause severe neonatal disease, suggesting additional mechanisms of placental translocation.
To investigate these virulence mechanisms, we adapted a physiologically relevant co-culture human placental barrier Transwell model composed of BeWo trophoblasts and primary human placental …
Optimal Control Strategies For Infectious Diseases: A Numerical Simulation Approach, M. Abu Salek, Jannatun Nayeem, Romana Yesmin, M. Haider Ali Biswas, M. Humayun Kabir
Optimal Control Strategies For Infectious Diseases: A Numerical Simulation Approach, M. Abu Salek, Jannatun Nayeem, Romana Yesmin, M. Haider Ali Biswas, M. Humayun Kabir
Mathematical Modelling and Numerical Simulation with Applications
Various infectious diseases, such as Tuberculosis and Hepatitis B virus (HBV), caused by Mycobacterium bacteria and hepatitis B virus, respectively, pose serious threats worldwide. This paper examines the spread of these diseases using a mathematical model that incorporates control measures, including vaccination and awareness programs. We use a system of differential equations with control variables and apply Pontryagin's principle to determine optimal control strategies. The stability of the Disease Free Equilibrium (DFE) has been analysed and demonstrated to be both locally and globally asymptotically stable when the basic reproduction number remains below unity, thereby ensuring disease elimination. Furthermore, the Endemic …
Effects Of Alk2 Deficiency On T Cell Fate And Regulatory T Cell Populations, Jalyn Reeves, Afia Salsabil Alam
Effects Of Alk2 Deficiency On T Cell Fate And Regulatory T Cell Populations, Jalyn Reeves, Afia Salsabil Alam
Knowledge and Creativity Expo
Regulatory T cells (Tregs) are central to immune tolerance, and their lineage stability is established during thymic development and maintained in the periphery through tightly regulated signaling networks. Members of the BMP receptor family have been implicated in T-cell differentiation, yet the specific role of the type I receptor ALK2 in shaping cell fate and sustaining the regulatory program remains unclear. To examine how ALK2 contributes to T-cell development, we generated ALK2-knockout murine chimeras and analyzed lymphoid populations from the thymus, spleen, and peripheral tissues. Thymocytes and lymphocytes were isolated and stained with antibody panels to identify developmental subsets and …
Fisheries Occasional Publication No. 151 - Response To 2025 External Review Of Integrated Stock Assessments For Key Wa Demersal Indicator Stocks, Brett Crisafulli, Emily A. Fisher, Matias Braccini, Rubie Evans-Powell, Fabian I. Trinnie, Ainslie Denham, S. A. Hesp
Fisheries Occasional Publication No. 151 - Response To 2025 External Review Of Integrated Stock Assessments For Key Wa Demersal Indicator Stocks, Brett Crisafulli, Emily A. Fisher, Matias Braccini, Rubie Evans-Powell, Fabian I. Trinnie, Ainslie Denham, S. A. Hesp
Fisheries Occasional Publications
Consistent with national trends, the Department of Primary Industries and Regional Development (DPIRD) is transitioning to the globally recognised Stock Synthesis (SS) platform to support more robust, transparent, and internationally aligned assessments. To ensure this transition remains scientifically sound, DPIRD commissioned an independent expert review in 2025, following a previous review in 2024. The 2025 review was conducted by Professor André Punt and focused on integrated models for three key WA fish stocks: red emperor in the Kimberley, WA dhufish in the southern West Coast Bioregion, and sandbar shark at the statewide level. This publication summarises the findings and recommendations …
Mitochondrial Transfer And Induced Ros As A Therapeutic Strategy In Idh2-Mutant Chondrosarcoma, Vegas R. Bedder, Caleb Wyckoff, Chris Osgood, Gavin A. Vasquez, Michael Stacey
Mitochondrial Transfer And Induced Ros As A Therapeutic Strategy In Idh2-Mutant Chondrosarcoma, Vegas R. Bedder, Caleb Wyckoff, Chris Osgood, Gavin A. Vasquez, Michael Stacey
Knowledge and Creativity Expo
Chondrosarcoma (CS) are common bone cancers that produce cartilaginous tumors and are extremely refractive to chemo-and-radiation therapies, leaving very limited treatment options. They contain mutations in the isocitrate dehydrogenase genes, IDH1 or IDH2. Either IDH1 or IDH2 mutations are present in individual tumors, but not both. They both convert alphaketoglutarate (αKG) into the potent oncometabolite D-2-hydroxyglutarate (D2HG). D2HG can be transported from the tumors to cells of the tumor microenvironment (TME) where it can alter metabolic and epigenetic profiles in recipient cells. The process of α-KG to D2HG conversion occurs in the cytoplasm of IDH1 mutant cells, and in the …
Tlr3 Mediated Type I Interferon Response In Mammalian Cell Defense Against Cryptosporidium Parvum Infection., Anjelica Matias
Tlr3 Mediated Type I Interferon Response In Mammalian Cell Defense Against Cryptosporidium Parvum Infection., Anjelica Matias
Biochemistry and Molecular Biology
Cryptosporidium parvum is a major cause of a diarrheal disease which affects many children in the USA as well as the rest of the world, yet the contribution of its double stranded RNA (dsRNA) viral symbiont, Cryspovirus (CSpV1) to host innate immunity remains unclear. This study investigated whether CSpV1 activates Toll Like Receptor 3 (TLR3) signaling pathways and downstream Interferon type I (IFN I) responses in mammalian intestinal epithelial cells. Confluent Human Ileocecal Colorectal Adenocarcinoma cells (HCT8) were exposed to CSpV1, and the expression levels of Tumor Necrosis Factor Receptor-Associated Factor 3 (TRAF3), Nuclear Factor-𝜅-light chain enhancer of activated B-cells …
Successful Treatment Of Juvenile Sterile Granulomatous Dermatitis And Lymphadenitis In A Pomeranian Aged 5 Months Using Topical Hydrocortisone Aceponate And Systemic Antibiotic, Nutjira Sawatmongkol, Sirada Tayayouth, Suttiwee Chermprapai
Successful Treatment Of Juvenile Sterile Granulomatous Dermatitis And Lymphadenitis In A Pomeranian Aged 5 Months Using Topical Hydrocortisone Aceponate And Systemic Antibiotic, Nutjira Sawatmongkol, Sirada Tayayouth, Suttiwee Chermprapai
The Thai Journal of Veterinary Medicine
A 5-month-old intact male Pomeranian puppy was presented with a 2-week history of acutely swollen face, eyelids, lips, and muzzle. A physical examination revealed focal alopecia, folliculitis, and erythema on the muzzle, periocular, and perianal areas; crusts were also found around the muzzle. The puppy received monthly oral afoxolaner and milbemycin oxime. No ectoparasite was observed based on a trichogram test. Skin cytology revealed intracellular cocci and neutrophils. A skin biopsy taken from the muzzle revealed pyogranulomatous perifollicular dermatitis with epidermal spongiosis, intraepidermal pustules, and a superficial crust. This condition was diagnosed as juvenile cellulitis on the basis of age, …
Filifactor Alocis Disrupts Efferocytosis To Sustain Inflammation In Periodontitis, Ella Dye, Silvia Uriarte, Ruth Idowu
Filifactor Alocis Disrupts Efferocytosis To Sustain Inflammation In Periodontitis, Ella Dye, Silvia Uriarte, Ruth Idowu
The Cardinal Edge
Background: Filifactor alocis is a Gram-positive, obligate anaerobe that has emerged as a diagnostic marker of periodontitis. Neutrophils and macrophages are key players in oral immune homeostasis. Neutrophils are short-lived cells and constitutively undergo apoptosis. This apoptotic program can be accelerated or delayed by bacterial interactions. Macrophages clear apoptotic neutrophils via “efferocytosis,” a crucial mechanism for resolving inflammation and preventing tissue damage. The efferocytic process downregulates the expression and release of proinflammatory cytokines such as interleukin (IL)-6 and IL-23 while promoting anti-inflammatory responses. Our previous findings demonstrated that F. alocis delays neutrophil apoptosis, with fewer apoptotic cells observed after 18 …
Ifnγ-Induced Antigen Loss In Chimeric Antigen Receptor-T Cell Therapy, Miao Cao, Jasmine Alvarez, Ramkrishna Mitra, Michael Xu, Trevor R. Baybutt, Zhengyang Sun, Oluwatobiloba Taylor, Allison Doermann, Ross E Staudt, Scott A. Waldman, Adam E. Snook
Ifnγ-Induced Antigen Loss In Chimeric Antigen Receptor-T Cell Therapy, Miao Cao, Jasmine Alvarez, Ramkrishna Mitra, Michael Xu, Trevor R. Baybutt, Zhengyang Sun, Oluwatobiloba Taylor, Allison Doermann, Ross E Staudt, Scott A. Waldman, Adam E. Snook
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
INTRODUCTION: FDA-approved chimeric antigen receptor (CAR)-expressing T cell therapies (CARTs) have revolutionized the treatment of blood cancers. Yet none have been successful for "solid" tumors, such as colorectal cancer (CRC), the 2nd leading cause of cancer deaths. Guanylyl cyclase C (GUCY2C) has emerged as a clinical-stage target for CART and bispecific T-cell engager (BiTE) therapies in CRC. IFNγ has been canonically recognized as beneficial for the effector functions of T cells by enhancing antigen processing and HLA presentation and is essential for CART targeting of solid malignancies by inducing adhesion molecule expression for synapse stabilization.
METHODS: Using
RESULTS: We identified …
Targeting Il-1 Signaling In Recessive Dystrophic Epidermolysis Bullosa: Improved Survival And Pathogenesis In Rdeb Mouse Model, Rahim Hirani
Targeting Il-1 Signaling In Recessive Dystrophic Epidermolysis Bullosa: Improved Survival And Pathogenesis In Rdeb Mouse Model, Rahim Hirani
NYMC Student Theses and Dissertations
Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating inherited blistering disorder caused by biallelic mutations in COL7A1, resulting in deficiency of type VII collagen (C7) and loss of dermal–epidermal adhesion. Beyond mechanical fragility, RDEB is characterized by chronic inflammation, progressive fibrosis, impaired wound healing, severe pain, and an exceptionally high risk of aggressive cutaneous squamous cell carcinoma. Emerging transcriptomic and cytokine profiling studies have identified interleukin-1 alpha (IL-1α) as a dominant and temporally upstream inflammatory mediator in RDEB skin. The central hypothesis of this dissertation is that IL-1α signaling functions as a key initiator and amplifier of inflammation-driven pathology …
Breaking Into Hiv-1'S Epigenetic Vault: Cure Strategies To Eliminate The Viral Reservoir, Joanna Jones, Chelsea Gunderson, Brian Wigdahl, Michael Nonnemacher
Breaking Into Hiv-1'S Epigenetic Vault: Cure Strategies To Eliminate The Viral Reservoir, Joanna Jones, Chelsea Gunderson, Brian Wigdahl, Michael Nonnemacher
Kimmel Cancer Center Faculty Papers
Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induce the killing of infected cells. "Block and Lock" uses …
A Survey-Based Exploratory Study Of Factors Influencing Women's Intentions To Utilise Pre-Exposure Prophylaxis In The Eastern Cape Province, South Africa: Sociodemographic Characteristics, Hiv Risk Behaviours And Transactional Sex, Rosemary Kalenga, Gary Sharp, Anne M. Teitelman, Monde Makiwane, Larry D. Icard, John B. Jemmott
A Survey-Based Exploratory Study Of Factors Influencing Women's Intentions To Utilise Pre-Exposure Prophylaxis In The Eastern Cape Province, South Africa: Sociodemographic Characteristics, Hiv Risk Behaviours And Transactional Sex, Rosemary Kalenga, Gary Sharp, Anne M. Teitelman, Monde Makiwane, Larry D. Icard, John B. Jemmott
College of Nursing Faculty Papers & Presentations
BACKGROUND: South Africa has the third-highest adult prevalence rate globally, with women comprising 64% of cases. Despite the accessibility of pre-exposure prophylaxis (PrEP), its adoption among women, particularly young women, remains alarmingly low.
OBJECTIVES: The objective of this initial investigation is to explore factors influencing the intentions of South African women to use PrEP, focusing on sociodemographic factors, HIV sexual risk behaviours and involvement in transactional sex.
DESIGN: The research utilised an exploratory design employing surveys.
METHODS: Surveys were conducted in 2015 with 64 women aged 19-49 residing in the Eastern Cape Province of South Africa. The data were analysed …
No Effect In Plasma Corticosterone Levels After Observation Of Diseased Conspecifics, B. M. Hardy, M. Chang, S. Mccallum, S. Santangelo, Patricia C. Lopes
No Effect In Plasma Corticosterone Levels After Observation Of Diseased Conspecifics, B. M. Hardy, M. Chang, S. Mccallum, S. Santangelo, Patricia C. Lopes
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Organisms commonly respond to stressors in their environment by increasing the secretion of corticosterone (CORT). While increased CORT is acknowledged as a response to predation risk by organisms inhabiting a landscape of fear, new research raises the potential for changes in CORT as a response to the risk of infection by organisms in their environment. An increase in CORT of a healthy, uninfected individual in response to their perception of the risk of infection in their environment could change their susceptibility to infection, highlighting a significant role for CORT to alter host–pathogen dynamics. To investigate the effects of infection risk …
Evaluation Of Il-10 And Il-12 As Early Diagnostic Biomarkers In Type 2 Diabetes Mellitus, Mariam Sami Shail, Israa Hussein Hamzah
Evaluation Of Il-10 And Il-12 As Early Diagnostic Biomarkers In Type 2 Diabetes Mellitus, Mariam Sami Shail, Israa Hussein Hamzah
Maaen Journal for Medical Sciences
Background: Type 2 diabetes mellitus (T2DM) is increasingly recognized as a complex metabolic disorder associated with immune dysregulation and chronic low-grade inflammation Objectives: This study aimed to quantify serum levels of (IL-10) and (IL-12) in patients with (T2DM) and to explore their potential role as early diagnostic biomarkers in comparison with healthy controls. Methods: A case–control study be situated showed including 120 participants: 80 patients with T2DM and 40 healthy controls. Serum concentrations of IL-10 and IL-12 were quantified using ELISA. Hematological and biochemical parameters were assessed using standard automated methods. Statistical analyses included independent t-tests, correlation analysis, and receiver …
Targeting Cancer With T Cells: Preclinical And In Silico Insights To Improve Immunotherapies, Nina Obertopp
Targeting Cancer With T Cells: Preclinical And In Silico Insights To Improve Immunotherapies, Nina Obertopp
USF Tampa Graduate Theses and Dissertations
T-cell–based immunotherapies are often constrained by limited trafficking and persistence in tumors and by functional exhaustion under chronic antigen exposure. This dissertation addresses these barriers through two distinct strategies: (i) preclinical studies testing how radiation therapy modulates tumor-infiltrating lymphocytes (TIL) therapy, and (ii) agent based modeling (ABM) to optimize treatment day treatment-free intervals (TFI) in T-cell engager (TCE) therapy. (i) In a human papillomavirus–positive (HPV⁺) head-and-neck cancer (HNC) model, a single local-dose of RT (8 Gy) delivered five days before tumor harvest increased the success and functional quality of ex vivo TIL outgrowth from tumor fragments, enriching polyfunctional CD8⁺ subsets. …
Fisheries Occasional Publication No. 150 - Response To 2024 External Review Of Integrated Stock Assessments For Key Wa Demersal Indicator Stocks, Rubie Evans-Powell, S. A. Hesp, Ainslie Denham, Emily A. Fisher, Rachel Marks, Fabian I. Trinnie, Brett Crisafulli
Fisheries Occasional Publication No. 150 - Response To 2024 External Review Of Integrated Stock Assessments For Key Wa Demersal Indicator Stocks, Rubie Evans-Powell, S. A. Hesp, Ainslie Denham, Emily A. Fisher, Rachel Marks, Fabian I. Trinnie, Brett Crisafulli
Fisheries Occasional Publications
In Western Australia (WA), stock assessments for key demersal species, including snapper and red emperor, have traditionally used bespoke integrated models developed in-house by the Department of Primary Industries and Regional Development (DPIRD). In line with other Australian jurisdictions, DPIRD is transitioning to Stock Synthesis (SS) as its primary platform for integrated stock assessments of WA finfish. To support this transition, DPIRD commissioned an independent expert review of recent integrated models applied to three demersal stocks. This publication responds to recommendations from Professor André Punt (University of Washington and CSIRO) in his 2024 review, which examined assessments for Pilbara red …
Cytotoxic And Antimicrobial Effects Of Plant-Derived Compounds Used In Traditional Chinese Medicine, Amanda Ly, Diane Sun, Shelbi Salinas, Victor M. Jimenez
Cytotoxic And Antimicrobial Effects Of Plant-Derived Compounds Used In Traditional Chinese Medicine, Amanda Ly, Diane Sun, Shelbi Salinas, Victor M. Jimenez
Annual Research Symposium
No abstract provided.
Mycobacteria Infection Induced Cascade Of Epigenetic Alterations Promote Training In Bystander Macrophages, Shah E. Jahan Gulzar Mr
Mycobacteria Infection Induced Cascade Of Epigenetic Alterations Promote Training In Bystander Macrophages, Shah E. Jahan Gulzar Mr
Theses and Dissertations
Mycobacterium tuberculosis (Mtb) remodels host cell functions to support its intracellular persistence. While the effects of Mtb infection on infected macrophages are well characterized, responses of uninfected bystander cells in the same microenvironment remain poorly understood. Here, we show that Mtb infection triggers widespread epigenetic reprogramming not only in infected macrophages but also in neighbouring bystander cells. These bystander macrophages acquire active chromatin marks, exhibit distinct transcriptional changes, and display enhanced immune responsiveness, thereby increasing resistance to both homologous and heterologous infections. We identify interleukin-1 beta secreted by infected cells as a key mediator of this process. Functionally, trained bystander …
Gene Regulatory Programs Of Nk Cells Show That Ncam1 (Cd56) And Kirs Are Controlled By Genetically Polymorphic Distal Regulatory Elements, Mariam A. Salem, Aditi Varkey, Matthew D. Estrada, Kruthika Sharma, Caprice D. Eisele, Nitin Chakravarti, Dean A. Lee, Aharon G. Freud, Bethany L. Mundy-Bosse, Patrick L. Collins
Gene Regulatory Programs Of Nk Cells Show That Ncam1 (Cd56) And Kirs Are Controlled By Genetically Polymorphic Distal Regulatory Elements, Mariam A. Salem, Aditi Varkey, Matthew D. Estrada, Kruthika Sharma, Caprice D. Eisele, Nitin Chakravarti, Dean A. Lee, Aharon G. Freud, Bethany L. Mundy-Bosse, Patrick L. Collins
Kimmel Cancer Center Faculty Papers
Owing to their immunoprotective properties, natural killer (NK) cells are critical for the innate immune response to pathogens, as well as a new wave of cancer immunotherapy that harnesses natural cytotoxicity. We sought to study the genetic and epigenetic drivers behind human-specific NK cell receptors, so that we can better understand the underlying cellular function. Here, we present a transcriptomic, proteomic (CITE-seq), and chromatin (single nuclei ATAC-seq) profiling of human peripheral NK cell subsets, which was then compared with genomic databases. Through integrative multi-omics, we demonstrate that CD56bright versus CD56dim NK cell subsets have differential distal regulatory element …
Immunogenicity And Efficacy Of A Rabies-Based Vaccine Against Highly Pathogenic Influenza H5n1 Virus, Nir Paran, Christoph Wirblich, Randy Albrecht, Leila Zabihi Diba, Alessandro Tarquinio, Drishya Kurup, Charalambos C. Solomides, Adolfo García-Sastre, Matthias J. Schnell
Immunogenicity And Efficacy Of A Rabies-Based Vaccine Against Highly Pathogenic Influenza H5n1 Virus, Nir Paran, Christoph Wirblich, Randy Albrecht, Leila Zabihi Diba, Alessandro Tarquinio, Drishya Kurup, Charalambos C. Solomides, Adolfo García-Sastre, Matthias J. Schnell
Department of Microbiology and Immunology Faculty Papers
The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV …
Combined Glycoprotein Mutations In Rabies Virus Promote Astrocyte Tropism And Protective Cns Immunity In Mice, Mirjam Anna Rita Bertoune, Corinna Kolbe, Ann-Cathrin Werner, Maren Steinmetz, Bernhard Dietzschold, Eberhard Weihe
Combined Glycoprotein Mutations In Rabies Virus Promote Astrocyte Tropism And Protective Cns Immunity In Mice, Mirjam Anna Rita Bertoune, Corinna Kolbe, Ann-Cathrin Werner, Maren Steinmetz, Bernhard Dietzschold, Eberhard Weihe
Department of Microbiology and Immunology Faculty Papers
Rabies virus (RABV) causes fatal encephalitis once it invades the central nervous system (CNS), and treatment options are extremely limited at this stage. We investigated the recombinant RABV variants SPBN, SPBNGA (glycoprotein substitution R333E), SPBNGAK (R333E plus N194K), SPBNGAS (R333E plus N194S), and TriGAS (three copies of the R333E/N194S glycoprotein). We evaluated their cellular tropism and immune activation in an intracerebral mouse infection model using immunohistochemistry and confocal immunofluorescence. SPBNGAK (R333E/N194K) resulted in mixed neuronal and astrocytic infection and lethal disease. In contrast, the R333E/N194S mutations in the GAS variants were associated with reduced neuronal infection and apparent astrocyte-restricted infection …
Phase 1b/2 Study Of Bms-813160, A Ccr2/5 Dual Antagonist, In Combination With Chemotherapy Or Nivolumab In Patients With Advanced Pancreatic Or Colorectal Cancer, Dung T. Le, Gunnar Folprecht, Anna M. Varghese, Martin Gutierrez, Marcus Noel, Nikolaos A. Trikalinos, Eric Chen, Farshid Dayyani, S. Lindsey Davis, Wen Wee Ma, Atrayee Basu Mallick, Ignacio Garrido-Laguna, Mayu Osawa, Shaun O'Brien, Ruslan D. Novosiadly, Ke Xu, Danielle M. Greenawalt, Santanu Dutta, Christina Twyman Saint Victor, Heinz-Josef Lenz
Phase 1b/2 Study Of Bms-813160, A Ccr2/5 Dual Antagonist, In Combination With Chemotherapy Or Nivolumab In Patients With Advanced Pancreatic Or Colorectal Cancer, Dung T. Le, Gunnar Folprecht, Anna M. Varghese, Martin Gutierrez, Marcus Noel, Nikolaos A. Trikalinos, Eric Chen, Farshid Dayyani, S. Lindsey Davis, Wen Wee Ma, Atrayee Basu Mallick, Ignacio Garrido-Laguna, Mayu Osawa, Shaun O'Brien, Ruslan D. Novosiadly, Ke Xu, Danielle M. Greenawalt, Santanu Dutta, Christina Twyman Saint Victor, Heinz-Josef Lenz
Department of Medical Oncology Faculty Papers
BACKGROUND: Cysteine-cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC.
METHODS: Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once …
Contribution To The Chemotherapy Of Human Trypanosomiasis: Design, Synthesis, And Biological Evaluation Of Dimeric 2-Nitroimidazoles Against Trypanosoma Cruzi Amastigotes And Bloodstream Trypanosoma Brucei, Afonso Santine M.M. Velez, Otavio Augusto Chaves, Carlos Serpa, Fatma M. Salem, Bibo Li Ph.D., Bin Su Ph.D., Celio Geraldo Freire-De-Lima, Debra Decote-Ricardo, Marco Edilson Freire De Lima
Contribution To The Chemotherapy Of Human Trypanosomiasis: Design, Synthesis, And Biological Evaluation Of Dimeric 2-Nitroimidazoles Against Trypanosoma Cruzi Amastigotes And Bloodstream Trypanosoma Brucei, Afonso Santine M.M. Velez, Otavio Augusto Chaves, Carlos Serpa, Fatma M. Salem, Bibo Li Ph.D., Bin Su Ph.D., Celio Geraldo Freire-De-Lima, Debra Decote-Ricardo, Marco Edilson Freire De Lima
Biological, Geological, and Environmental Faculty Publications
Effective and safe treatments for neglected tropical diseases caused by parasites, such as Chagas disease and sleeping sickness, remain lacking, posing a significant challenge for researchers worldwide. The rational design of dimeric compounds inspired solely by the pharmacophoric core of benznidazole (2-nitroimidazole) has proven to be a promising strategy for antiparasitic development. Thus, in the present work, it was increased the linker between the active units (2-nitroimidazole) to improve the interaction with TcNTR, facilitating the bioactivation of the longest dimers. Biological assays confirmed this, demonstrating that all compounds were active against replicative intracellular amastigotes of Trypanosoma cruzi (Tulahuen C2C4-LacZ). Notably, …
A Probabilistic Modeling Analysis Of The Longitudinal Immune Response To Infection And Vaccination Across Demographic Groups And Pulmonary Symptoms, James O'Hanlon, Kaitlyn Sullivan, Lyndsey M. Muehling, Glenda Canderan, Jie Sun, Judith A. Woodfolk, Jeffrey M. Wilson, Rayanne A. Luke
A Probabilistic Modeling Analysis Of The Longitudinal Immune Response To Infection And Vaccination Across Demographic Groups And Pulmonary Symptoms, James O'Hanlon, Kaitlyn Sullivan, Lyndsey M. Muehling, Glenda Canderan, Jie Sun, Judith A. Woodfolk, Jeffrey M. Wilson, Rayanne A. Luke
Spora: A Journal of Biomathematics
Antibody and cytokine kinetics describe the dynamic response to immune events such as infection and vaccination. These dynamics are not fully understood, and mathematical characterization may help explain variability across demographic groups and pulmonary symptoms post-acute infection. We fit time-dependent probability models to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data to obtain distributions of longitudinal antibody response and cytokine values. To assess differences between groups, an overlap metric is applied to the modeled response curves. Our antibody models suggest significant differences between male and female populations and demonstrate deficient antibody responses of less-healthy groups such as smokers. Our cytokine …
Decoding Early Covid-19 Responses Using Mathematical Modeling Of Social Distancing Strategies Across Multiple Countries, Sri Gunturu, Suki Lewis, Katelyn Nguyen, Asma Azizi
Decoding Early Covid-19 Responses Using Mathematical Modeling Of Social Distancing Strategies Across Multiple Countries, Sri Gunturu, Suki Lewis, Katelyn Nguyen, Asma Azizi
Spora: A Journal of Biomathematics
During the early phase of the COVID-19 pandemic, before vaccines were available, countries implemented diverse combinations of social-distancing (SD) measures shaped by cultural norms and public acceptance. These differences produced varied outcomes in controlling viral spread, offering lessons for future health-crisis preparedness. We performed a reverse-engineering analysis of early COVID-19 case data from five socioculturally distinct countries—India, Vietnam, Italy, Finland, and the United States—selected to capture a range of initial prevalence levels. Using mathematical modeling and data fitting, we inferred the relative contributions of three SD interventions: face masking, quarantine, and isolation of infected individuals. We then employed an efficiency …
Surveillance Of A Novel Vesivirus Discovered In An Urban Mephitis Mephitis Population, Amanda E. Diggins
Surveillance Of A Novel Vesivirus Discovered In An Urban Mephitis Mephitis Population, Amanda E. Diggins
Honors Theses and Capstones
Caliciviridae is a family of non-enveloped, positive-sense, single stranded RNA viruses, including eleven defined genera that contain important pathogens of humans and animals. Within the Caliciviridae family, the genus Vesiviridae includes feline calicivirus, a leading cause of upper respiratory disease in cats, and vesicular exanthema of swine virus, a historical disease of domestic swine that has now been implicated in several marine mammal vesicular diseases, one of which has been confirmed zoonotic. Urban landscapes create a unique environment for rapid intra- and interspecies transmission of viruses. Clustered resources attract high-density populations of synanthropic wildlife species, increasing spatial overlap and heightening …
Tick Lipocalin Triggers Mammalian Igfbp-3-Mediated Apoptosis In Macrophages And Keratinocytes, Krittika Nandy, P. P. Mahesh, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta
Tick Lipocalin Triggers Mammalian Igfbp-3-Mediated Apoptosis In Macrophages And Keratinocytes, Krittika Nandy, P. P. Mahesh, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta
Biological Sciences Faculty Publications
Ticks secrete several molecules, including lipocalins, in their saliva during blood feeding on a vertebrate host. In this study, we provide novel evidence on the role of Ornithodoros turicata americanus tick lipocalin (Otlip) in modulating cytokine expression and in triggering apoptosis in mammalian macrophages and keratinocytes. The cytokine array analysis revealed significantly increased secretion of insulin-like growth factor-binding protein 3 (IGFBP3) from murine macrophage cell line upon treatment with recombinant Otlip protein (rGST-Otlip) when compared to the secretion noted from cells treated with a control protein (rGST). Similar observation with cytokine protein array analysis was noted when murine macrophages were …