Generation and Characterization of a Multi-Functional Panel of Monoclonal Antibodies for SARS-CoV-2 Research and Treatment.

The Coronavirus disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is an ongoing threat to global public health. To this end, intense efforts are underway to develop reagents to aid in diagnostics, enhance preventative measures, and provide therapeutics for managing COVID-19. The recent emergence of SARS-CoV-2 Omicron variants with enhanced transmissibility, altered antigenicity, and significant escape of existing monoclonal antibodies and vaccines underlines the importance of the continued development of such agents.

Differential Transcriptome Responses in Human THP-1 Macrophages Following Exposure to T98G and LN-18 Human Glioblastoma Secretions: A Simplified Bioinformatics Approach to Understanding Patient-Glioma-Specific Effects on Tumor-Associated Macrophages.

A common theme in glioma disease progression is robust infiltration of immune cells within the tumor microenvironment, resulting in a state of chronic inflammation. This disease state is characterized by an abundance of CD68 microglia and CD163 bone marrow-derived macrophages with the greater the percentage of CD163 cells, the poorer the prognosis. These macrophages are "cold," in that their phenotype is of an alternatively activated state (M0-M2-like) supporting tumor growth rather than being engaged with classically activated, pro-inflammatory, and anti-tumor activities, referred to as "hot", or M1-like.

Development and Applications of a Zebrafish () CYP1A-Targeted Monoclonal Antibody (CRC4) with Reactivity across Vertebrate Taxa: Evidence for a Conserved CYP1A Epitope.

CYP1A is a heme-thiolate enzyme associated with the cytochrome P4501A1 monooxygenase system and is inducible by a wide variety of xenobiotics and endogenous ligands that bind and activate the aryl hydrocarbon receptor (AHR). The AHR-CYP1A axis is important for detoxification of certain xenobiotics and for homeostatic balance of endogenous sex hormones, amine hormones, vitamins, fatty acids, and phospholipids. Herein, we generated and described applications of a zebrafish CYP1A-targeted monoclonal antibody (mAb CRC4) that fortuitously recognizes induced CYP1A across vertebrate taxa, including fish, chicken, mouse, rat, and human.

Chronic toxicity of tire crumb rubber particles to mummichog (Fundulus heteroclitus) in episodic exposures.

Microrubber (MR) encompasses all tire-related particles in the micro-scale and has recently drawn increased attention as a subclass of the broader group of microplastics. While tire particles entered the environment since the introduction of rubber tires for vehicles, the concern regarding tire wear particles (TWP) as an environmental contaminant is relatively new. Recent studies have examined physical and chemical toxicity of MR particles and leachates to a variety of organisms.

Quantifying Circulating IgY Antibody Responses against Select Opportunistic Bacterial Pathogens and Correlations with Body Condition Factors in Wild American Alligators, .

Little is known about the disease ecology of American alligators (), and especially how they respond immunologically to emerging infectious diseases and zoonotic pathogens. In this study, we examined serum samples collected from wild alligators in Florida (2010-2011) and South Carolina (2011-2012, 2014-2017) for antibody responses to multiple bacteria. Immunoglobulin Y (IgY) was purified from serum to generate a mouse monoclonal antibody (mAb AMY-9) specific to the IgY heavy chain.

Reversal of elastase-induced abdominal aortic aneurysm following the delivery of nanoparticle-based pentagalloyl glucose (PGG) is associated with reduced inflammatory and immune markers.

Objective: An Abdominal aortic aneurysm (AAA), a deadly disease in elderly population, is featured by expansion of aortic diameter, degradation and weakening of vasculature. Its common and significant characteristics are disarray and inflammation in vasculature. We tested the hypothesis that the reversal of abdominal aortic aneurysm by pentagalloyl glucose-loaded nanoparticles (PGG-NPs) therapy that targets degraded elastin suppresses inflammatory and immune markers to ameliorate the pathophysiology of the disease in advance stage aneurysm in a porcine pancreatic elastase (PPE)-induced mouse model of AAA.

Quantifying circulating antibody activities against the emerging environmental pathogen, in wild captured bull sharks, spotted eagle rays, bottlenose dolphins, and loggerhead turtles.

Global and related pathogen infections are increasing, and place both wildlife species and humans at risk. Notably, is now considered to be an emerging and zoonotic pathogen. Mouse monoclonal antibodies (mAbs) were generated against bull shark, , and spotted eagle ray, , IgM, and bottlenose dolphin, , IgG.

The In Vitro Proinflammatory Properties of Water Accommodated Sediment Extracts from a Creosote-Contaminated US Environmental Protection Agency Superfund Site.

The southern branch of the Elizabeth River near Portsmouth, Virginia, USA, is one of the most creosote-polluted subestuaries in North America and the former location of the Atlantic Wood US Environmental Protection Agency Superfund site. We previously demonstrated that adult Atlantic Wood killifish collected in situ had severe hepatic lesions, including hepatoblastoma and hepatocellular carcinoma, as well as suppressed circulating antibody responses compared to a historical reference site. Moreover, several innate immune functions were higher in Atlantic Wood fish, including elevated expression of hepatic cyclooxygenase-2 (COX-2), suggesting a proinflammatory environment.

20th Pollutant Responses in Marine Organisms (PRIMO 20): Global issues and fundamental mechanisms caused by pollutant stress in marine and freshwater organisms.

The 20th Pollutant Responses in Marine Organisms (PRIMO 20) conference provided a forum for scientists from around the world to communicate novel toxicological research findings specifically focused on aquatic organisms, by combining applied and basic research at the intersection of environmental and mechanistic toxicology. The work highlighted in this special issue of Aquatic Toxicology, a special issue of Marine Environmental Research, and presented through posters and presentations, encompass important and emerging topics in freshwater and marine toxicology. This includes multiple types of emerging contaminants including microplastics and UV filtering chemicals.

Modulation of glioma-inflammation crosstalk profiles in human glioblastoma cells by indirubin-3'-(2,3 dihydroxypropyl)-oximether (E804) and 7-bromoindirubin-3'-oxime (7BIO).

Indirubins E804 (indirubin-3'-(2,3 dihydroxypropyl)-oximether) and 7BIO (7-Bromoindirubin-3'-oxime) are synthetic derivatives of natural indirubin, the active compound in Danggui Longhui Wan, a traditional Chinese remedy for cancer and inflammation. Herein, we explore E804 and 7BIO for their potential to modulate key pro-inflammatory genes and cytokines in LN-18 and T98G glioblastoma cells. High grade gliomas typically secrete large amounts of inflammatory cytokines and growth factors that promote tumor growth in an autocrine fashion.

Comparative Innate and Adaptive Immune Responses in Atlantic Bottlenose Dolphins () With Viral, Bacterial, and Fungal Infections.

Free-ranging Atlantic bottlenose dolphins ( = 360) from two southeastern U.S. estuarine sites were given comprehensive health examinations between 2003 and 2015 as part of a multi-disciplinary research project focused on individual and population health.

Monoclonal antibodies against loggerhead sea turtle, Caretta caretta, IgY isoforms reveal differential contributions to antibody titers and relatedness among other sea turtles.

Serum from loggerhead sea turtles, Caretta caretta, was collected from the southeast Atlantic Ocean during routine summer monitoring studies in 2017. Serum immunoglobulin IgY was purified and used to develop IgY isoform-specific monoclonal antibodies (mAb). mAb LH12 was developed against the 66 kDa heavy chain of IgY, mAb LH1 was developed against the truncated heavy chain of approximately 37 kDA, and mAb LH9 was developed against the 23 kDa light chains.

Humoral Immune Responses to Select Marine Bacteria in Loggerhead Sea Turtles Caretta caretta and Kemp's Ridley Sea Turtles Lepidochelys kempii from the Southeastern United States.

Serum from Kemp's ridley sea turtles Lepidochelys kempii and loggerhead sea turtles Caretta caretta was collected during summer in 2011, 2012, and 2013. Serum immunoglobulin Y (IgY) recognition of lysate proteins from nine bacterial species and whole bacterium-specific IgY titers to these pathogens were quantified. Serum and purified IgY recognized proteins of all bacteria, with protein recognition for some species being more pronounced than others.

Expression of the Major Vault Protein (MVP) and Cellular Vault Particles in Fish.

Cellular vaults are ubiquitous 13 mega Da multi-subunit ribonuceloprotein particles that may have a role in nucleocytoplasmic transport. Seventy percent of the vault's mass consists of a ≈100 kDa protein, the major vault protein (MVP). In humans, a drug resistance-associated protein, originally identified as lung resistance protein in metastatic lung cancer, was ultimately shown to be the previously described MVP.

Biomarkers of Aryl-hydrocarbon Receptor Activity in Gulf Killifish (Fundulus grandis) From Northern Gulf of Mexico Marshes Following the Deepwater Horizon Oil Spill.

Following the Deepwater Horizon oil spill, shorelines throughout the Barataria Basin of the northern Gulf of Mexico in Louisiana were heavily oiled for months with Macondo-252 oil, potentially impacting estuarine species. The Gulf killifish (Fundulus grandis) has been identified as a sentinel species for the study of site-specific effects of crude oil contamination on biological function. In November and December 2010, 4-5 months after the Macondo well was plugged and new oil was no longer spilling into the Gulf waters, Gulf killifish were collected across the Barataria Basin from 14 sites with varying degrees of oiling.

The environment as a driver of immune and endocrine responses in dolphins (Tursiops truncatus).

Immune and endocrine responses play a critical role in allowing animals to adjust to environmental perturbations. We measured immune and endocrine related markers in multiple samples from individuals from two managed-care care dolphin groups (n = 82 samples from 17 dolphins and single samples collected from two wild dolphin populations: Indian River Lagoon, (IRL) FL (n = 26); and Charleston, (CHS) SC (n = 19). The immune systems of wild dolphins were more upregulated than those of managed-care-dolphins as shown by higher concentrations of IgG and increases in lysozyme, NK cell function, pathogen antibody titers and leukocyte cytokine transcript levels.

AHR-related activities in a creosote-adapted population of adult atlantic killifish, Fundulus heteroclitus, two decades post-EPA superfund status at the Atlantic Wood Site, Portsmouth, VA USA.

Atlantic killifish, Fundulus heteroclitus, are adapted to creosote-based PAHs at the US EPA Superfund site known as Atlantic Wood (AW) on the southern branch of the Elizabeth River, VA USA. Subsequent to the discovery of the AW population in the early 1990s, these fish were shown to be recalcitrant to CYP1A induction by PAHs under experimental conditions, and even to the time of this study, killifish embryos collected from the AW site are resistant to developmental deformities typically associated with exposure to PAHs in reference fish. Historically, however, 90 +% of the adult killifish at this site have proliferative hepatic lesions including cancer of varying severity.

3,4-Dihydroxy-benzohydroxamic acid (Didox) suppresses pro-inflammatory profiles and oxidative stress in TLR4-activated RAW264.7 murine macrophages.

Didox (3,4-dihydroxy-benzohydroxamic acid), is a synthetic ribonucleotide reductase (RR) inhibitor derived from polyhydroxy-substituted benzohydroxamic acid, and originally developed as an anti-cancer agent. Some studies indicate that didox may have anti-oxidative stress-like properties, while other studies hint that didox may have anti-inflammatory properties. Using nitric oxide production in response to LPS treatment as a sensitive screening assay for anti-inflammatory compounds, we show that didox is very potent at levels as low as 6.

Identification and characterization of membrane androgen receptors in the ZIP9 zinc transporter subfamily: I. Discovery in female atlantic croaker and evidence ZIP9 mediates testosterone-induced apoptosis of ovarian follicle cells.

Rapid, cell surface-initiated, pregenomic androgen actions have been described in various vertebrate cells, but the receptors mediating these actions remain unidentified. We report here the cloning and expression of a cDNA from Atlantic croaker (Micropogonias undulatus) ovaries encoding a 33-kDa, seven-transmembrane protein with binding and signaling characteristics of a membrane androgen receptor that is unrelated to any previously described steroid receptor. Instead, croaker membrane androgen receptor has 81-93% amino acid sequence identity with zinc transporter ZIP9 (SLC39A9) subfamily members, indicating it is a ZIP9 protein.

Clinicoimmunopathologic findings in Atlantic bottlenose dolphins Tursiops truncatus with positive Chlamydiaceae antibody titers.

Sera from free-ranging Atlantic bottlenose dolphins Tursiops truncatus inhabiting the Indian River Lagoon (IRL), Florida, and coastal waters of Charleston (CHS), South Carolina, USA, were tested for antibodies to Chlamydiaceae as part of a multidisciplinary study of individual and population health. A suite of clinicoimmunopathologic variables was evaluated in Chlamydiaceae-seropositive dolphins (n = 43) and seronegative healthy dolphins (n = 83). Fibrinogen, lactate dehydrogenase, amylase, and absolute numbers of neutrophils, lymphocytes, and basophils were significantly higher, and serum bicarbonate, total alpha globulin, and alpha-2 globulin were significantly lower in dolphins with positive Chlamydiaceae titers compared with seronegative healthy dolphins.

Multitissue molecular, genomic, and developmental effects of the Deepwater Horizon oil spill on resident Gulf killifish (Fundulus grandis).

The Deepwater Horizon oil rig disaster resulted in crude oil contamination along the Gulf coast in sensitive estuaries. Toxicity from exposure to crude oil can affect populations of fish that live or breed in oiled habitats as seen following the Exxon Valdez oil spill. In an ongoing study of the effects of Deepwater Horizon crude oil on fish, Gulf killifish ( Fundulus grandis ) were collected from an oiled site (Grande Terre, LA) and two reference locations (coastal MS and AL) and monitored for measures of exposure to crude oil.

Indirubin-3'-(2,3 dihydroxypropyl)-oximether (E804) is a potent modulator of LPS-stimulated macrophage functions.

Indirubin is a deep-red bis-indole isomer of indigo blue, both of which are biologically active ingredients in Danggui Longhui Wan, an ancient Chinese herbal tea mixture used to treat neoplasia and chronic inflammation and to enhance detoxification of xenobiotics. Multiple indirubin derivatives have been synthesized and shown to inhibit cyclin-dependent kinases (CDKs) and glycogen-synthase kinase (GSK-3β) with varying degrees of potency. Several indirubins are also aryl hydrocarbon receptor (AhR) agonists, with AhR-associated activities covering a wide range of potencies, depending on molecular structure.

Clinicoimmunopathologic findings in Atlantic bottlenose dolphins Tursiops truncatus with positive cetacean morbillivirus antibody titers.

Sera from free-ranging Atlantic bottlenose dolphins Tursiops truncatus inhabiting the Indian River Lagoon (IRL), Florida were tested for antibodies to cetacean morbilliviruses from 2003 to 2007 as part of a multidisciplinary study of individual and population health. A suite of clinicoimmunopathologic variables were evaluated in morbillivirus-seropositive dolphins (n = 14) and seronegative healthy dolphins (n = 49). Several important differences were found.

Genomic and physiological footprint of the Deepwater Horizon oil spill on resident marsh fishes.

The biological consequences of the Deepwater Horizon oil spill are unknown, especially for resident organisms. Here, we report results from a field study tracking the effects of contaminating oil across space and time in resident killifish during the first 4 mo of the spill event. Remote sensing and analytical chemistry identified exposures, which were linked to effects in fish characterized by genome expression and associated gill immunohistochemistry, despite very low concentrations of hydrocarbons remaining in water and tissues.