A NOVEL ROLE FOR HDL AND D-HDL IN PULMONARY IMMUNITY

Cardiovascular and pulmonary diseases are leading causes of morbidity and mortality worldwide. Studies report an inverse correlation between levels of serum high-density lipoprotein (HDL) and the severity of cardiovascular and lung diseases. HDL has also been shown to be anti-inflammatory, anti-atherosclerotic, and anti-oxidative. HDL's cardioprotective functions are well understood through the reverse cholesterol transport process. However, how HDL effects the immune system in the lungs is still unknown. We hypothesize that HDL is critical in preventing pulmonary injury from lipopolysaccharide (LPS) through inhibiting neutrophil (PMN) chemotaxis. While HDL is known to be biologically protective, it has also been reported that HDL can become dysfunctional (D-HDL) in chronic inflammatory diseases. HDL is characterized as dysfunctional when it does not perform its protective mechanisms. It has been challenging to study D-HDL, in part, because D-HDL is found in specific patient populations commonly burdened with comorbidities and subsequent medications. Apolipoprotein A-I (apoA-I), the major protein component of HDL, is primarily responsible for HDL's beneficial properties. There are apoA-I mimetic peptides, such as L-4F, available to study the biological properties of HDL in both in vitro and in vivo models. However, there is no such research tool available to study D-HDL. Therefore, to better understand how D-HDL differs from HDL, we also sought to design a D-HDL mimetic peptide that can be used to examine the biological mechanisms of how HDL and D-HDL differ

Camel Digital Necropsy Guide

Jaundice / Icterus Jaundice / icterus is yellowing of tissue due to elevated bilirubin levels. The tissue under the skin and on the surfaces of the stomachs and intestines is normally white to cream colored. If it is yellow, the animal is jaundiced/icteric. Three processes can lead to jaundice: 1. Over-production of bilirubin due to increased red blood cell destruction, 2. Liver disease, and 3. Bile duct obstruction. In a jaundiced animal, carefully assess the liver. If the liver appears normal, the jaundice may be due to increased red blood cell (erythrocyte) destruction, which can occur with certain blood parasites, such as anaplasmosis. Note that the dromedaries do not have a gall bladder

RNAseq Reveals Complex Response of Campylobacter jejuni to Ovine Bile and In vivo Gallbladder Environment

Colonization of the gallbladder by enteric pathogens such as Salmonella typhi, Listeria monocytogenes, and Campylobacter jejuni is thought to play a key role in transmission and persistence of these important zoonotic agents; however, little is known about the molecular mechanisms that allow for bacterial survival within this harsh environment. Recently, a highly virulent C. jejuni sheep abortion (SA) clone represented by the clinical isolate IA3902 has emerged as the dominant cause for sheep abortion in the United States. Previous studies have indicated that the C. jejuni clone SA can frequently be isolated from the gallbladders of otherwise healthy sheep, suggesting that the gallbladder may serve as an important reservoir for infection. To begin to understand the molecular mechanisms associated with survival in the host gallbladder, C. jejuni IA3902 was exposed for up to 24 h to both the natural ovine host in vivo gallbladder environment, as well as ovine bile in vitro. Following exposure, total RNA was isolated from the bile and high throughput deep sequencing of strand specific rRNA-depleted total RNA was used to characterize the transcriptome of IA3902 under these conditions. Our results demonstrated for the first time the complete transcriptome of C. jejuni IA3902 during exposure to an important host environment, the sheep gallbladder. Exposure to the host environment as compared to in vitro bile alone provided a more robust picture of the complexity of gene regulation required for survival in the host gallbladder. A subset of genes including a large number of protein coding genes as well as seven previously identified non-coding RNAs were confirmed to be differentially expressed within our data, suggesting that they may play a key role in adaptation upon exposure to these conditions. This research provides valuable insights into the molecular mechanisms that may be utilized by C. jejuni IA3902 to colonize and survive within the inhospitable gallbladder environment

Pathogenicity of an emergent, ovine abortifacient Campylobacter jejuni clone orally inoculated into pregnant guinea pigs

Objective—To compare pathogenicity of an emergent abortifacient Campylobacter jejuni (IA 3902) with that of reference strains after oral inoculation in pregnant guinea pigs. Animals—58 pregnant guinea pigs. Procedures—12 animals were challenged IP with C jejuni IA 3902 along with 5 sham-inoculated control animals to confirm abortifacient potential. Once pathogenicity was confirmed, challenge via oral inoculation was performed whereby 12 guinea pigs received IA 3902, 12 received C jejuni isolated from ovine feces (OF48), 12 received a fully sequenced human C jejuni isolate (NCTC 11168), and 5 were sham-inoculated control animals. After abortions, guinea pigs were euthanized; samples were collected for microbial culture, histologic examination, and immunohistochemical analysis. Results—C jejuni IA 3902 induced abortion in all 12 animals following IP inoculation and 6 of 10 animals challenged orally. All 3 isolates colonized the intestines after oral inoculation, but only IA 3902 induced abortion. Evidence of infection existed for both IA 3902 and NCTC 11168; however, C jejuni was only recovered from fetoplacental units of animals inoculated with IA 3902. Immunohistochemical analysis localized C jejuni IA 3902 infection to subplacental trophoblasts, perivascular tissues, and phagocytes in the placental transitional zone. Conclusions and Clinical Relevance—This study revealed that C jejuni IA 3902 was a unique, highly abortifacient strain with the ability to colonize the intestines, induce systemic infection, and cause abortion because of its affinity for the fetoplacental unit. Guinea pigs could be effectively used in the study of septic abortion after oral inoculation with this Campylobacter strain

Earth as a Transiting Exoplanet: A Validation of Transmission Spectroscopy and Atmospheric Retrieval Methodologies for Terrestrial Exoplanets

The James Webb Space Telescope (JWST) will enable the search for and characterization of terrestrial exoplanet atmospheres in the habitable zone via transmission spectroscopy. However, relatively little work has been done to use solar system data, where ground truth is known, to validate spectroscopic retrieval codes intended for exoplanet studies, particularly in the limit of high resolution and high signal-to-noise (S/N). In this work, we perform such a validation by analyzing a high S/N empirical transmission spectrum of Earth using a new terrestrial exoplanet atmospheric retrieval model with heritage in Solar System remote sensing and gaseous exoplanet retrievals. We fit the Earth's 2-14 um transmission spectrum in low resolution (R=250 at 5 um) and high resolution (R=100,000 at 5 um) under a variety of assumptions about the 1D vertical atmospheric structure. In the limit of noiseless transmission spectra, we find excellent agreement between model and data (deviations < 10%) that enable the robust detection of H2O, CO2, O3, CH4, N2, N2O, NO2, HNO3, CFC-11, and CFC-12 thereby providing compelling support for the detection of habitability, biosignature, and technosignature gases in the atmosphere of the planet using an exoplanet-analog transmission spectrum. Our retrievals at high spectral resolution show a marked sensitivity to the thermal structure of the atmosphere, trace gas abundances, density-dependent effects, such as collision-induced absorption and refraction, and even hint at 3D spatial effects. However, we used synthetic observations of TRAPPIST-1e to verify that the use of simple 1D vertically homogeneous atmospheric models will likely suffice for JWST observations of terrestrial exoplanets transiting M dwarfs.Comment: 37 pages, 14 figures, 9 tables. Accepted for publication in PS

Glucose Reaction with Fumonisin B1 Partially Reduces Its Toxicity in Swine

Acute and subacute intraperitoneal doses of fumonisin B1 (FB1) were administered to test the efficacy of the FB1-glucose reaction products in detoxifying FB1 in swine. In the acute study at 11 µmol of FB1/kg of body weight, five of six pigs administered FB1 and four of six pigs administered FB1- glucose died from acute pulmonary edema. Analysis of weight gain, serum aspartate aminotransferase and γ-glutamyltransferase, total cholesterol, and pathological evaluation did not provide evidence of protection against FB1 toxicity by the FB1-glucose reaction products. In the subacute study at 5.5 µmol of FB1/kg of body weight, one pig administered FB1 died from liver damage. Analysis of serum aspartate aminotransferase, γ-glutamyltransferase, and total bilirubin showed protection against FB1 toxicity by the FB1-glucose reaction products. The levels of sphinganine and sphinganine/sphingosine ratios in serum and liver as well as pathologic findings provided definitive evidence of protection against the FB1 toxic effects by this detoxification procedure (p \u3c 0.05)

Comparison of two commercial ovine Campylobacter vaccines and an experimental bacterin in guinea pigs inoculated with Campylobacter jejuni

Objective—To compare efficacy of 2 commercial ovine Campylobacter vaccines and an experimental bacterin in guinea pigs following IP inoculation with Campylobacter jejuni IA3902. Animals—51 female guinea pigs. Procedures—Pregnant and nonpregnant animals were randomly assigned to 1 of 4 treatment groups and administered a commercial Campylobacter vaccine labeled for prevention of campylobacteriosis in sheep via two 5-mL doses 14 days apart (vaccine A; n = 13), another labeled for prevention of campylobacteriosis via two 2-mL doses (vaccine B; 12), an experimental bacterin prepared from the challenge strain (12), or a sham vaccine (14). Ten days later, animals were challenged IP with C jejuni IA3902; 48 hours later, animals were euthanized, complete necropsy was performed, and blood and tissue samples were obtained for bacteriologic culture. Results—Administration of vaccine B or the experimental bacterin, but not vaccine A, significantly reduced 48-hour infection rates versus administration of the sham vaccine. A significantly reduced 48-hour infection rate was associated with administration of vaccine B independent of pregnancy status. Conclusions and Clinical Relevance—Administration of vaccine B significantly reduced infection in guinea pigs challenged with C jejuni IA3902, similar to a homologous bacterin. Results suggested that vaccine B or an autogenous product may be effective in controlling ovine campylobacteriosis caused by this emergent abortifacient strain. Bacteriologic culture of blood, liver, bile, and uterus in nonpregnant guinea pigs 48 hours after inoculation may be a useful screening tool for comparing efficacy of C jejuni vaccines

Fumonisin B-Glucose Reaction Products Are Less Toxic When Fed to Swine

The effects of fumonisin B-glucose reaction products in swine diets was examined. Pigs were fed diets containing 528 µmol of total fumonisin B/kg (FB), 528 µmol of total FB-glucose adducts/kg (FB-G, 122 µmol of unreacted FB/kg), or 0 µmol of total FB/kg for 15 days to test the efficacy of the FB-G reaction products in detoxifying FB. Weight gain in FB pigs was lower than in FB-G or controls, which was correlated with feed intake reduction in FB pigs. Serum aspartate aminotransferase, γ-glutamyltransferase, and total bilirubin in FB pigs were higher than in FB-G or control pigs. Serum sphinganine/shingosine ratios in FB pigs were higher than in FB-G or control pigs. Microscopic examination of tissues from FB pigs showed generalized liver necrosis and apoptosis with marked cellular pleomorphism and disorganized hepatic cords. The liver and kidneys in the FB-G group appeared to be normal. Tissues of controls were free of lesions. Results suggest that dietary FB-G products are less toxic to swine and may provide an detoxification approach in instances of widespread FB grain contamination (p \u3c 0.05)