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Immunology and Infectious Disease

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Obesity As A Risk Factor For Covid-19, Gabriela Hermes, Mir Saleem Aug 2022

Obesity As A Risk Factor For Covid-19, Gabriela Hermes, Mir Saleem

Mako: NSU Undergraduate Student Journal

The coronavirus pandemic has presented a wide range of challenges for healthcare systems in the world. COVID-19 has infected millions of people, with approximately 90% of the population showing mild or no symptoms. The disease has some risk factors that increase its severity, such as obesity, age, diabetes, cardiovascular diseases, suppressed immune system, and pulmonary disorders. Obese individuals have higher chances of having symptomatic COVID-19 infection with excessive rates of hospitalization and ICU admission. Understanding the mechanisms defining the link between COVID-19 and obesity is necessary to develop preventive measures and therapeutic interventions for people with obesity. Patients with obesity …


An Ecological And Physiological Assessment Of Feather Mite-Bird Symbioses, Kevin James Krajcir Aug 2022

An Ecological And Physiological Assessment Of Feather Mite-Bird Symbioses, Kevin James Krajcir

Student Theses and Dissertations

Feather mites are ectosymbiotic arthropods that reside primarily on the wing and tail feathers of most birds. Despite our growing understanding of feather mite biology, previous studies of the nature of the feather mite-avian host relationship report mutualism, parasitism, and commensalism. Such inconsistencies are likely due to narrow study designs that fail to capture the possibility of context dependency in this interaction. To provide some clarity surrounding the nature of this symbiotic system, we explored how geographical, climatic, and ecological contexts relate to variation in feather mite abundance and how that abundance, consequently, associates with multiple metrics of host condition …


Intrinsic Cardiac Effects Of Severe Acute Respiratory Syndrome Coronavirus 2 In Coronavirus Disease 2019, Brittany Danielle Brumback Aug 2022

Intrinsic Cardiac Effects Of Severe Acute Respiratory Syndrome Coronavirus 2 In Coronavirus Disease 2019, Brittany Danielle Brumback

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiac arrhythmias, particularly ventricular arrhythmias, can be life-threatening and caused by both congenital genetic mutations and acquired cardiac injury. My thesis work was originally focused on delineating the effects of genetic mutation-driven dysregulation of a protein called Hey2 in Brugada Syndrome, a complex disease characterized by a predisposition to dangerous arrhythmias originating in the right ventricular outflow tract. In response to the pandemic, my thesis work shifted toward understanding the mechanisms of cardiovascular injury in Coronavirus disease 2019 (COVID-19), which is associated with serious cardiovascular complications, including ventricular arrhythmias and sudden cardiac death as well as endothelial dysfunction and coagulopathies. …


Investigating Host Defenses Of North American Salamanders Against The Recently Emerged Chytrid Pathogen, Batrachochytrium Salamandrivorans, Kenzie Pereira Aug 2022

Investigating Host Defenses Of North American Salamanders Against The Recently Emerged Chytrid Pathogen, Batrachochytrium Salamandrivorans, Kenzie Pereira

Electronic Theses and Dissertations

A recently emerged chytrid fungal pathogen, Batrachochytrium salamandrivorans (Bsal) threatens salamander biodiversity. Bsal susceptibility varies between and within salamander species, but little is known about the mechanisms underlying these differences. Susceptibility is likely influenced by numerous interacting factors, but my dissertation studied the role of host immune responses.

My first aim investigated between species differences by studying the bioactive properties of salamander skin peptides against Bsal and the related pathogen, B. dendrobatidis (Bd). Skin peptides were collected from five salamander species, used for in vitro assays, and analyzed by RP-HPLC. While skin peptides from one …


Neural Stem Cells: Age-Dependent Outcomes During Viral Infections In The Central Nervous System, Manisha N. Chandwani Aug 2022

Neural Stem Cells: Age-Dependent Outcomes During Viral Infections In The Central Nervous System, Manisha N. Chandwani

Electronic Theses and Dissertations

Viral infections in the central nervous system (CNS) are associated with neurodevelopmental and neurobehavioral deficits. The outcomes of viral infections can be driven by damage and death of neurons. Neural stem cells (NSCs) play key roles in neurodevelopment, repair, and physiological brain function. During a viral infection, NSC activity can disturbed by direct infection of NSCs by the virus or by anti-viral immune response. Here, we aimed to assess whether the anti-viral immune response can impact NSC activity during an immunocompetent response in the adult brain. We utilized a transgenic mouse model of Measles virus infection where only the CNS …


Investigating The Role Of Splenic Macrophages In Pancreatic Cancer, Daisy V. Gonzalez Aug 2022

Investigating The Role Of Splenic Macrophages In Pancreatic Cancer, Daisy V. Gonzalez

Theses & Dissertations

Pancreatic cancer is currently the 3rd leading cause of all cancer-related deaths, with a 5-year survival rate remaining at 10%. The current standard treatment of care and a lack of effective diagnostic markers leaves patients with a dismal prognosis at advanced stages of the disease. This thesis research evaluated the effect of ApoE-expressing macrophages in the spleen. First, we aimed to assess the ApoE expression in the spleen of pancreatic tumor-bearing mice. Results showed that ApoE expression in splenic macrophages increased as the disease progressed. In addition, we saw a significant increase in marginal zone metallophilic macrophages and red pulp …


Qualitative Interviews To Understand Health Care Providers’ Experiences Of Prescribing Licensed Peanut Oral Immunotherapy, Aikaterini Anagnostou, Claire Lawrence, Stephen A Tilles, Susan Laubach, Sarah M Donelson, Mohamed Yassine, Anna Nowak-Wegrzyn Aug 2022

Qualitative Interviews To Understand Health Care Providers’ Experiences Of Prescribing Licensed Peanut Oral Immunotherapy, Aikaterini Anagnostou, Claire Lawrence, Stephen A Tilles, Susan Laubach, Sarah M Donelson, Mohamed Yassine, Anna Nowak-Wegrzyn

Faculty, Staff and Students Publications

OBJECTIVE: This research sought to explore health care providers' (HCPs) experiences of delivering the first US Food and Drug Administration (FDA) and European Commission (EC) approved peanut oral immunotherapy (peanut OIT; Palforzia). Semi-structured qualitative interviews with HCPs who had initiated treatment with ≥ 3 patients in the first nine months following FDA approval sought to identify challenges faced and successful implementation strategies.

RESULTS: Eight allergists and three nurse practitioners from eight sites based in the United States participated. The HCPs included in this research were motivated to implement this novel treatment, however, entered the process with some reservations. HCPs described …


Anticipating Infection: How Parasitism Risk Changes Animal Physiology, Patricia C. Lopes Aug 2022

Anticipating Infection: How Parasitism Risk Changes Animal Physiology, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

  1. Uninfected animals can attempt to prevent parasitism in many ways. Behavioural avoidance of parasitized conspecifics, for instance, is documented in several species.
  2. Interactions with parasitized conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well studied, and consequently, less well understood. The way in which exposure to parasitism risk changes the physiology of uninfected animals and the impacts of those changes on animal fitness remain a significant gap in knowledge.
  3. Determining how the disease environment experienced by animals impacts their physiology, survival and reproduction has major implications for our knowledge of how …


A Checklist Of Parasites Of Peromyscus Maniculatus In North America, John Ubelaker, Gábor R. Rácz Aug 2022

A Checklist Of Parasites Of Peromyscus Maniculatus In North America, John Ubelaker, Gábor R. Rácz

MANTER: Journal of Parasite Biodiversity

This document represents a summary of parasites, in the broadest sense of the term, reported from Peromyscus maniculatus from throughout its range in North America. The document provides data from work ranging from paleontological findings to relatively current reports of parasites and parasitism from P. maniculatus and covers viruses, bacteria sensu lato, protists, helminths, and ectoparasites.


Perception Of Illness And Its Association With Willingness To Adhere To Treatment In Chronic Hepatitis C Patients With New Diagnosis Of Nonalcoholic Fatty Liver Disease, Carmel Kruse Aug 2022

Perception Of Illness And Its Association With Willingness To Adhere To Treatment In Chronic Hepatitis C Patients With New Diagnosis Of Nonalcoholic Fatty Liver Disease, Carmel Kruse

The Eleanor Mann School of Nursing DNP Capstone Projects

Chronic liver disease is becoming the most common cause of mortality, morbidity, and utilization of healthcare services globally. Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) are frequent causes of chronic liver disease. Recently, there have been significant findings on the relationship between NAFLD and CHC; patients with CHC have a higher incidence of NAFLD. The introduction of direct-acting antivirals has cured more CHC patients than ever before. Unfortunately, the current interventions for NAFLD requiring behavioral change remain ineffective. Patient’s ability to follow advice depends largely on their health beliefs; therefore, understanding their illness perception is an …


Mitochondrial Dna Diversity, Parasite And Pathogen Occurrence, And A Potential Disease Vector In Managed And Unmanaged Honey Bee, Apis Mellifera L. Populations, Dylan Cleary Aug 2022

Mitochondrial Dna Diversity, Parasite And Pathogen Occurrence, And A Potential Disease Vector In Managed And Unmanaged Honey Bee, Apis Mellifera L. Populations, Dylan Cleary

Graduate Theses and Dissertations

The western honey bee, Apis mellifera L., is a globally important pollinator plagued by several harmful stressors impacting colony health and survival. At least eight A. mellifera subspecies were imported and continue to be the genetic ancestors of U.S. honey bee populations today. Successive genetic bottle-neck events have led to reduced genetic diversity in U.S. honey bees. First, the subset of subspecies imported into the U.S. represents only a third of A. mellifera subspecies. Next, the parasitic varroa mite reduced managed and feral populations. Third, ongoing breeding practices have selected for traits from a single genetic lineage and bred from …


Investigating Granulopoiesis Of Neutrophils From Myeloblasts In The Bone Marrow Post Novel Anti-Schistosoma Compound Treatment, Sarah Alsuleiman, Paul Davis Aug 2022

Investigating Granulopoiesis Of Neutrophils From Myeloblasts In The Bone Marrow Post Novel Anti-Schistosoma Compound Treatment, Sarah Alsuleiman, Paul Davis

Theses/Capstones/Creative Projects

Schistosomiasis, a commonly neglected tropical disease, is a waterborne parasitic worm infection able to infect through direct skin penetration. This disease affects approximately 270 million people worldwide and ranks only second to malaria as a leading infectious disease. Although some possible alternatives are emerging, currently, the most effective drug treatment is praziquantel (PZQ). However, PZQ is only effective against the adult stage of the worm, allowing juvenile worms to progress in the infection. Additionally, Schistosoma worms are developing resistance to this drug as reduced efficacy has been noted. Thus, the need for drug discovery and testing is increased. SA01, a …


Investigations Into Avian Skeletal Adaptations And Spine Fusion Events, Tori Huey Aug 2022

Investigations Into Avian Skeletal Adaptations And Spine Fusion Events, Tori Huey

All Theses

Avian dinosaurs evolved skeletal adaptations resulting in numerous fused spinal structures, like the synsacrum, present in extant birds. The synsacrum is a highly fused region necessary for stiffening the spine, and it fuses the spine to the pelvic ilium. Conventional wisdom suggests that fusion occurred in ovo during embryonic development via the cartilage matrix that patterns the future vertebrae. We show that post hatch birds have intervertebral discs separating all vertebrae of the spine, leading us to re-examine this notion in chickens up to 10 weeks of age. Intervertebral discs undergo constant remodeling, then degenerate and undergo tissue clearance, followed …


A Microfluidics-Based Approach For Isolation Of Antigen-Specific Cd8+ T Cells, Meredith Frank Aug 2022

A Microfluidics-Based Approach For Isolation Of Antigen-Specific Cd8+ T Cells, Meredith Frank

Dissertations and Theses (Open Access)

Cancer is a global epidemic: there are predicted to be 200 million new cases this year alone. Almost a quarter of all cancer-related deaths are caused by lung cancer, for which 5-year survival rates are just above 20%. 85% of lung cancer diagnoses are classified as non-small cell lung cancer (NSCLC) for which 5-year survival rates in metastatic disease are less than 10%. Early detection and targeted therapies have improved prognoses, yet relapse is still common among patients.

Immunotherapies that leverage tumor-specific CD8+ cytotoxic T cells have shown great promise for the treatment of NSCLC. However, although highly promising, …


The Influences Of Disperser Behavior, Host Availability, And Environmental Conditions On The Distribution Of Oak Mistletoe [Phoradendron Leucarpum (Raf.) Reveal & M. C. Johnst.] In Eastern Virginia And North Carolina, Nicholas Pearce Flanders Aug 2022

The Influences Of Disperser Behavior, Host Availability, And Environmental Conditions On The Distribution Of Oak Mistletoe [Phoradendron Leucarpum (Raf.) Reveal & M. C. Johnst.] In Eastern Virginia And North Carolina, Nicholas Pearce Flanders

Biological Sciences Theses & Dissertations

Mistletoes are shrubs that typically parasitize the branches of host trees and rely on avian frugivores for seed dispersal. Because mistletoes are restricted to a narrow range of suitable recruitment sites and avian frugivores are more visible than other guilds of seed dispersers, mistletoe-frugivore systems afford opportunities for assessing the roles of dispersal limitation and local environment in determining plant distribution. These mechanisms have been proposed as determinants of the observed association of oak mistletoe [Phoradendron leucarpum (Raf.) Reveal & M. C. Johnst.] with forested wetlands in eastern Virginia and North Carolina, USA. I tested the alternative hypothesis that …


The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia Aug 2022

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …


Infection And Transmission Determinants Of Flea-Borne Rickettsioses, Hanna J. Laukaitis Aug 2022

Infection And Transmission Determinants Of Flea-Borne Rickettsioses, Hanna J. Laukaitis

Graduate Theses and Dissertations (2019 - present)

The genus Rickettsia is comprised of Gram-negative, obligate intracellular bacteria that are spread by hematophagous arthropods. Elucidating the factors conferring rickettsial virulence has perplexed investigators for decades, complicated by the lack of efficient genetic tools necessary to uncover rickettsial- and vector-specific factors contributing to persistence. The advent of transposon mutagenesis has enabled the field to make vast developments in uncovering novel rickettsial mechanisms utilized in various host backgrounds. Thus, the aim of this study was to generate Rickettsia felis transposon mutants and characterize novel phenotypes associated with genetic disruption in an arthropod background. Distribution of rickettsiae is reliant on the …


Eluication Of Lipid Metabolic Pathways In Differentiating Giardia Lamblia Using High Resolution Mass Spectrometry, Cameron Ellis Aug 2022

Eluication Of Lipid Metabolic Pathways In Differentiating Giardia Lamblia Using High Resolution Mass Spectrometry, Cameron Ellis

Open Access Theses & Dissertations

Giardia lamblia is an intestinal protozoan found worldwide, including the U.S. This parasite exists in two morphologic stages - a replicative trophozoite and a relatively dormant yet viable cyst. While exposures of cysts to gastric acid during passage through the human stomach induces excystation, factors in the small intestine, where trophozoites colonize trigger encystation or cyst formation. Transformation into cyst stage is essential for Giardia to survive in the environment for months before infecting new hosts. Because of its small genome size (11.7 Mb), metabolic pathways in Giardia are highly reduced. As far as lipid metabolism is concerned, only limited …


Functional Characterization Of The Toxoplasma Gondii Endolysosomal System, Leah Brock Thornton Aug 2022

Functional Characterization Of The Toxoplasma Gondii Endolysosomal System, Leah Brock Thornton

All Dissertations

Toxoplasma gondii is an obligate intracellular parasite that can infect a wide range of mammalian hosts. T. gondii can cause severe disease in immunocompromised individuals as well as pregnant women, in which congenital toxoplasmosis can lead to spontaneous abortion and fetal blindness. T. gondii infects up to roughly one-third of the global human population and is the causative agent of toxoplasmosis. Given this health burden of toxoplasmosis and that antibiotics currently used for the treatment of infection lead to strong side effects, identification of parasite-specific targets are necessary for novel therapeutic strategies.

T. gondii parasites contain a dynamic and active …


Immunotherapeutic Effects Of Intratumorally Injected Zymosan-Adenovirus Conjugates Encoding Constant Active Irfs In A Melanoma Mouse Model, Margaret Musick Aug 2022

Immunotherapeutic Effects Of Intratumorally Injected Zymosan-Adenovirus Conjugates Encoding Constant Active Irfs In A Melanoma Mouse Model, Margaret Musick

All Dissertations

Current immunotherapies are only effective in a fraction of cancer patients. One of the main contributing factors to therapy resistance and overall poor prognosis is the immune status of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) have been shown to have significant influence on the immune status of the TME. As key players in maintaining tissue homeostasis, macrophages exhibit a broad range of phenotypes and functions, making TAMs a promising target for immunomodulatory therapies. As liaisons between innate and adaptive immunity, TAMs can promote a robust anti-tumor response involving both innate and adaptive immunity. This study investigated the potential of …


Performance Evaluation Of The Xt Microslide Assay Pairs On The Vitros Xt 7600 Compared To Vitros Single Microslide Assays On Vitros 5600, Lily Olayinka, Estella Tam, Sridevi Devaraj Aug 2022

Performance Evaluation Of The Xt Microslide Assay Pairs On The Vitros Xt 7600 Compared To Vitros Single Microslide Assays On Vitros 5600, Lily Olayinka, Estella Tam, Sridevi Devaraj

Faculty, Staff and Students Publications

OBJECTIVES: Pediatric hospitals are always challenged by specimen volumes and thus any innovation in this realm is very welcome. With the introduction of Microslide assay pairs, we aimed to evaluate the analytical performance of the Vitros XT MicroSlide assay pairs on the Vitros XT 7600 compared to single MicroSlides.

DESIGN: Performance characteristics included within-run precision, analytical measurable range, method comparison, and interference verification. We compared six XT MicroSlide pairs on the Vitros XT 7600 with twelve corresponding single slide assays on the Vitros 5600 system.

RESULTS: The XT MicroSlides on Vitros XT 7600 demonstrated excellent precision, equivalent analytical measurable range, …


Conventional And Advanced Mr Imaging Findings In A Cohort Of Pathology-Proven Dermoid Cysts Of The Pediatric Scalp And Skull, Bettina L Serrallach, Gunes Orman, M John Hicks, Nilesh Desai, Stephen Kralik, Thierry Agm Huisman Aug 2022

Conventional And Advanced Mr Imaging Findings In A Cohort Of Pathology-Proven Dermoid Cysts Of The Pediatric Scalp And Skull, Bettina L Serrallach, Gunes Orman, M John Hicks, Nilesh Desai, Stephen Kralik, Thierry Agm Huisman

Faculty, Staff and Students Publications

BACKGROUND: In the pediatric population, dermoid cysts are among the most frequent lesions of the scalp and skull. Imaging plays a key role in characterizing scalp and skull lesions in order to narrow the differential diagnoses. In general, dermoids are described as heterogeneous T1-/T2-hypo- to hyperintense lesions on magnetic resonance imaging.

METHODS: The goal of this retrospective study is to evaluate the diffusion weighted imaging findings while reviewing the conventional T1-/T2-/T1+C-weighted MR characteristics in a pathology-proven series of 14 dermoids of the pediatric scalp and skull.

RESULTS: In our pediatric cohort (eight boys, six girls, age range 3-95 months), half …


Glutathione Peroxidase 2 Is A Metabolic Driver Of The Tumor Immune Microenvironment And Immune Checkpoint Inhibitor Response, Kazi Mokim Ahmed, Ratna Veeramachaneni, Defeng Deng, Nagireddy Putluri, Vasanta Putluri, Maria F Cardenas, David A Wheeler, William K Decker, Andy I Frederick, Sawad Kazi, Andrew G Sikora, Vlad C Sandulache, Mitchell J Frederick Aug 2022

Glutathione Peroxidase 2 Is A Metabolic Driver Of The Tumor Immune Microenvironment And Immune Checkpoint Inhibitor Response, Kazi Mokim Ahmed, Ratna Veeramachaneni, Defeng Deng, Nagireddy Putluri, Vasanta Putluri, Maria F Cardenas, David A Wheeler, William K Decker, Andy I Frederick, Sawad Kazi, Andrew G Sikora, Vlad C Sandulache, Mitchell J Frederick

Faculty, Staff and Students Publications

BACKGROUND: The existence of immunologically 'cold tumors' frequently found across a wide spectrum of tumor types represents a significant challenge for cancer immunotherapy. Cold tumors have poor baseline pan-leukocyte infiltration, including a low prevalence of cytotoxic lymphocytes, and not surprisingly respond unfavorably to immune checkpoint (IC) inhibitors. We hypothesized that cold tumors harbor a mechanism of immune escape upstream and independent of ICs that may be driven by tumor biology rather than differences in mutational neoantigen burden.

METHODS: Using a bioinformatic approach to analyze TCGA (The Cancer Genome Atlas) RNA sequencing data we identified genes upregulated in cold versus hot …


Clinical Outcomes Of Patients With Recurrent Microsatellite-Stable Endometrial Cancer In Early-Phase Immunotherapy Clinical Trials, Jeffrey A How, Amir A Jazaeri, Siqing Fu, Jordi Rodon Ahnert, Jing Gong, Bettzy Stephen, Hanna Ferreira Dalla Pria, Priya Bhosale, Amber Johnson, Ying Yuan, Funda Meric-Bernstam, Aung Naing Jul 2022

Clinical Outcomes Of Patients With Recurrent Microsatellite-Stable Endometrial Cancer In Early-Phase Immunotherapy Clinical Trials, Jeffrey A How, Amir A Jazaeri, Siqing Fu, Jordi Rodon Ahnert, Jing Gong, Bettzy Stephen, Hanna Ferreira Dalla Pria, Priya Bhosale, Amber Johnson, Ying Yuan, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

Recurrent microsatellite stable (MSS) endometrial cancer has poor response to conventional therapy and limited efficacy with immune checkpoint monotherapy. We conducted a retrospective study of recurrent MSS endometrial cancer patients enrolled in immunotherapy-based clinical trials at MD Anderson Cancer Center between 1 January 2010 and 31 December 2019. Patients were evaluated for radiologic response using RECIST 1.1 criteria, progression-free survival (PFS), and overall survival (OS). Thirty-five patients were treated with immune checkpoint inhibitors: 8 with monotherapy, 17 with immunotherapy (IO) in combination with another IO-only, and 10 with IO in combination with non-IO therapy. Among those treated with combination IO …


Targeting De Novo Lipogenesis And The Lands Cycle Induces Ferroptosis In Kras-Mutant Lung Cancer, Caterina Bartolacci, Cristina Andreani, Gonçalo Vale, Stefano Berto, Margherita Melegari, Anna Colleen Crouch, Dodge L Baluya, George Kemble, Kurt Hodges, Jacqueline Starrett, Katerina Politi, Sandra L Starnes, Daniele Lorenzini, Maria Gabriela Raso, Luisa M Solis Soto, Carmen Behrens, Humam Kadara, Boning Gao, Ignacio I Wistuba, John D Minna, Jeffrey G Mcdonald, Pier Paolo Scaglioni Jul 2022

Targeting De Novo Lipogenesis And The Lands Cycle Induces Ferroptosis In Kras-Mutant Lung Cancer, Caterina Bartolacci, Cristina Andreani, Gonçalo Vale, Stefano Berto, Margherita Melegari, Anna Colleen Crouch, Dodge L Baluya, George Kemble, Kurt Hodges, Jacqueline Starrett, Katerina Politi, Sandra L Starnes, Daniele Lorenzini, Maria Gabriela Raso, Luisa M Solis Soto, Carmen Behrens, Humam Kadara, Boning Gao, Ignacio I Wistuba, John D Minna, Jeffrey G Mcdonald, Pier Paolo Scaglioni

Faculty, Staff and Student Publications

Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, …


Solid-State Nmr Analysis Of Unlabeled Fungal Cell Walls From Aspergillus And Candida Species, Liyanage D. Fernando, Malitha C. Dickwella Widanage, S. Chandra Shekar, Frederic Mentink-Vigier, Ping Wang, Sungsool Wi, Tuo Wang Jul 2022

Solid-State Nmr Analysis Of Unlabeled Fungal Cell Walls From Aspergillus And Candida Species, Liyanage D. Fernando, Malitha C. Dickwella Widanage, S. Chandra Shekar, Frederic Mentink-Vigier, Ping Wang, Sungsool Wi, Tuo Wang

School of Medicine Faculty Publications

Fungal infections cause high mortality in immunocompromised individuals, which has emerged as a significant threat to human health. The efforts devoted to the development of antifungal agents targeting the cell wall polysaccharides have been hindered by our incomplete picture of the assembly and remodeling of fungal cell walls. High-resolution solid-state nuclear magnetic resonance (ss NMR) studies have substantially revised our understanding of the polymorphic structure of polysaccharides and the nanoscale organization of cell walls in Aspergillus fumigatus and multiple other fungi. However, this approach requires 13C/15N-enrichment of the sample being studied, severely restricting its application. Here we employ the dynamic …


Review Of The Cloacininae Stossich (Nemata: Strongyloidea) From Australasian Marsupials (Marsupialia: Macropodoidea), Ian Beveridge, Lesley R. Smales Jul 2022

Review Of The Cloacininae Stossich (Nemata: Strongyloidea) From Australasian Marsupials (Marsupialia: Macropodoidea), Ian Beveridge, Lesley R. Smales

MANTER: Journal of Parasite Biodiversity

The nematode sub-family Cloacininae from Australasian macropodoid marsupials is reviewed. Keys are provided to all genera and species currently known. A revised definition of the sub-family and detailed generic diagnoses are provided. For each species, full synonymies and literature citations are included along with known hosts, geographical distributions and associated DNA sequence data. A brief morphological synopsis of each species is provided together with illustrations of the morphological features needed for identification using the keys. Due to uncertainties relating to the division of the sub-family into tribes, only the nominal allocation to tribe is provided. Two new genera are erected, …


The Testis-Specific E3 Ubiquitin Ligase Rnf133 Is Required For Fecundity In Mice, Kaori Nozawa, Yoshitaka Fujihara, Darius J Devlin, Ricardo E Deras, Katarzyna Kent, Irina V Larina, Kohei Umezu, Zhifeng Yu, Courtney M Sutton, Qiuji Ye, Laura K Dean, Chihiro Emori, Masahito Ikawa, Thomas X Garcia, Martin M Matzuk Jul 2022

The Testis-Specific E3 Ubiquitin Ligase Rnf133 Is Required For Fecundity In Mice, Kaori Nozawa, Yoshitaka Fujihara, Darius J Devlin, Ricardo E Deras, Katarzyna Kent, Irina V Larina, Kohei Umezu, Zhifeng Yu, Courtney M Sutton, Qiuji Ye, Laura K Dean, Chihiro Emori, Masahito Ikawa, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

BACKGROUND: Ubiquitination is a post-translational modification required for a number of physiological functions regulating protein homeostasis, such as protein degradation. The endoplasmic reticulum (ER) quality control system recognizes and degrades proteins no longer needed in the ER through the ubiquitin-proteasome pathway. E2 and E3 enzymes containing a transmembrane domain have been shown to function in ER quality control. The ER transmembrane protein UBE2J1 is a E2 ubiquitin-conjugating enzyme reported to be essential for spermiogenesis at the elongating spermatid stage. Spermatids from Ube2j1 KO male mice are believed to have defects in the dislocation step of ER quality control. However, associated …


Choline Supplementation Modifies The Effects Of Developmental Alcohol Exposure On Immune Responses In Adult Rats, Jessica A. Baker, Kristen R. Breit, Tamara S. Bodnar, Joanne Weinberg, Jennifer D. Thomas Jul 2022

Choline Supplementation Modifies The Effects Of Developmental Alcohol Exposure On Immune Responses In Adult Rats, Jessica A. Baker, Kristen R. Breit, Tamara S. Bodnar, Joanne Weinberg, Jennifer D. Thomas

Psychology Faculty Publications

Prenatal alcohol exposure can disrupt the development of numerous systems, including the immune system. Indeed, alterations in cytokine levels may contribute to the neuropathological, behavioral, and cognitive problems, and other adverse outcomes observed in individuals with fetal alcohol spectrum disorders. Importantly, supplementation with the essential nutrient choline can improve performance in hippocampal-dependent behaviors; thus, the present study examined the effects of choline on plasma and hippocampal cytokines in adult rats exposed to ethanol in early development. From postnatal day (PD) 4-9 (third trimester equivalent), pups received ethanol (5.25 g/kg/day) or Sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) …


Redirecting Host Preexisting Influenza A Virus Immunity For Cancer Immunotherapy, Bharat K R Chaganty, Songbo Qiu, Yang Lu, Gabriel Lopez-Berestein, Bulent Ozpolat, Zhen Fan Jul 2022

Redirecting Host Preexisting Influenza A Virus Immunity For Cancer Immunotherapy, Bharat K R Chaganty, Songbo Qiu, Yang Lu, Gabriel Lopez-Berestein, Bulent Ozpolat, Zhen Fan

Faculty, Staff and Student Publications

We tested the concept that host preexisting influenza A virus immunity can be redirected to inhibit tumor growth and metastasis through systemic administration of influenza A virus-related peptides to targeted tumors. Mice infected with influenza A virus strain A/Puerto Rico/8/34 (PR8) were used as a model of a host with preexisting viral immunity. The extent to which preexisting influenza A immunity in PR8-immunized mice can be redirected to inhibit tumor growth and metastasis was first examined by ectopic expression of influenza A nucleoprotein (NP) and hemagglutinin (HA) in syngeneic mammary tumor cells via lentiviral transduction. Then, the feasibility of implementing …