Background:There remains a need for animal models with human translatability in lung cancer (LC) research. Findings in pigs have high impact on humans due to similar anatomy and physiology. We present the characterization of a bronchoscopically-induced LC model in Oncopigs carrying inducible KRASG12D and TP53R167H mutations. Methods:Twelve Oncopigs underwent 29 injections via flexible bronchoscopy. Eighteen Adenovirus-Cre recombinase gene (AdCre) inductions were performed endobronchially (n=6) and transbronchially with a needle (n=12). Eleven control injections were performed without AdCre. Oncopigs underwent serial contrast-enhanced chest CT with clinical follow-up for 29 weeks. Following autopsy, lung and organ tissues underwent histopathology, immunohistochemistry, and RNA-sequencing with comparative analysis with The Cancer Genome Atlas (TCGA) human LC data. Results:All 18 sites of AdCre injections had lung consolidations on CT imaging. Transbronchial injections led to histopathologic invasive cancer and/or carcinoma in situ (CIS) in 11/12 (91.7%), and invasive cancer (excluding CIS) in 8/12 (66.6%). Endobronchial inductions led to invasive cancer in 3/6 (50%). A soft tissue metastasis was observed in one Oncopig. Immunohistochemistry confirmed expression of Pan-CK+/epithelial cancer cells, with macrophages and T cells infiltration in the tumor microenvironment. Transcriptome comparison showed 54.3% overlap with human LC (TCGA), in contrast to 29.88% overlap of KRAS-mutant mouse LC with human LC. Conclusions:The transgenic and immunocompetent Oncopig model has a high rate of LC following bronchoscopic transbronchial induction. Overlap of the Oncopig LC transcriptome with human LC transcriptome was noted. This pig model is expected to have high clinical translatability to the human LC patient.

Objective: Our objective was to evaluate how a particular zeolite-based flow agent affected ergot alkaloid digestion and physiological markers associated with fescue toxicosis. Materials and Methods: Twenty-four steers (226 +/- 27.6 kg) were used to test effects of enhanced zeolite-based flow agent (KALLSIL, Kemin Industries, Des Moines, IA) on ergot-like alkaloid digestion. Treatments were control (E+) or enhanced zeolite inclusion (E+Z; 2 g/kg, DM basis). Steers were limit-fed diets (1.8% of BW, DM basis) containing 465 mu g of ergovaline/kg of DM. Rectal temperature and respiration rate were recorded daily at 0700 and 1200 h from steers in a room kept at 18.5 degrees C +/- 0.33 degrees C, 32.6% +/- 2.19% relative humidity. Blood was collected on d 1, 7, 14, and 21 to measure prolactin. On d 21 prolactin stores were measured following infusion of thyrotropinreleasing hormone (TRH; 1 mu g/kg BW). Feces and urine were collected every 8 h from d 17 to 20, with 2-h advancement daily for digestibility, N balance, and recovery of ergot-like alkaloids. Results and Discussion: Digestion and N balance were not affected by treatment. Zeolite did not affect fecal recovery of ergovaline. Serum prolactin declined over time. Serum prolactin was greater in steers fed E+Z. Following TRH infusion, prolactin was numerically greater for E+Z. Rectal temperatures and respiration rates were not affected by E+Z. Implications and Applications: Under the conditions of this experiment, addition of this particular zeolite

Current genome sequencing technologies have made it possible to generate highly contiguous genome assemblies for non-model animal species. Despite advances in genome assembly methods, there is still room for improvement in the delineation of specific gene features in the genomes. Here we present genome visualization and annotation tools to support seven livestock species (bovine, chicken, goat, horse, pig, sheep, and water buffalo), available in a new resource called AgAnimalGenomes. In addition to supporting the manual refinement of gene models, these browsers provide visualization tracks for hundreds of RNAseq experiments, as well as data generated by the Functional Annotation of Animal Genomes (FAANG) Consortium. For species with predicted gene sets from both Ensembl and RefSeq, the browsers provide special tracks showing the thousands of protein-coding genes that disagree across the two gene sources, serving as a valuable resource to alert researchers to gene model issues that may affect data interpretation. We describe the data and search methods available in the new genome browsers and how to use the provided tools to edit and create new gene models.

Injection of bromocriptine mesylate has been used to mimic the symptoms of tall fescue toxicosis in beef cattle. Twelve steers (351 ± 11.82 kg) were used to investigate the effect of bromocriptine mesylate and heat stress on serum prolactin, rectal temperature, respiration rate, and innate/adaptive immune function. Steers were randomly assigned to receive an injection of saline (CON) or bromocriptine mesylate (BROMO; 0.1mg/kg BW) every three days. Animals were housed for 22 d in the Brody Climatology Laboratory at thermoneutrality (TN; 19.5±0.26°C; 10-d) before transitioning (2-d) to heat stress (HS; 27.2±0.26°C nighttime, 34.5±0.26°C daytime; 10-d). Cattle were fed 1.8% of BW (DM-basis) daily across two feedings. Rectal temperatures and respiration rates were measured daily at 0600, 0900, 1500, and 1800 h. Serum and plasma were harvested from blood collected on d 1, 9, and 21 (9th d of thermoneutrality and heat stress, respectively) and analyzed for prolactin and cytokines. Dry-matter intake was not affected by treatment (P=0.52) or temperature (P=0.78). Prolactin concentrations decreased (P=0.02) throughout the trial and decreased (P< 0.01) with BROMO. Rectal temperature and respiration rate were greater (P< 0.01) for BROMO during TN and HS. Rectal temperature and respiration rate were increased (P< 0.01) during HS. Pro-inflammatory cytokine (TNF-α, IFN-α, IFN-γ, IL-1α, IL-1β, IL-17, and IL-18) concentrations were greater (P< 0.01) for BROMO steers than CON. Heat stress increased (P< 0.01) pro-inflammatory cytokines with the exception of IL-18 (P=0.98) regardless of treatment. Anti-inflammatory cytokines (IL-13, IL-1-F5, IL-21, IFN-β, LIF) were decreased (P< 0.07) for BROMO steers with the exception of IL-10 (P=0.58). Regardless of treatment IL-13, IL-21, IL-10, and LIF concentrations were greater (P< 0.05) during HS. These results demonstrate that bromocriptine mesylate successfully mimicked the symptoms of fescue toxicosis. Innate and adaptive immune responses were influenced by treatment and temperature, potentially affecting beef cattle immune competency.