Rattus Model Utilizing Selective Pulmonary Ischemia Induces Bronchiolitis Obliterans Organizing Pneumonia

Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. Studies were performed 7 days later. Relative pulmonary and systemic flow to each lung was measured by injection of technetium Tc 99m macroaggregated albumin. Histological sections were examined for structure and necrosis and scored for BOOP. Apoptosis was detected by immunohistochemistry with an antibody against cleaved caspase 3. Pulmonary artery blood flow to left lungs was less than 0.1% of the cardiac output, and bronchial artery circulation was ~2% of aortic artery flow. Histological sections from ischemic left lungs consistently showed Masson bodies, inflammation, and young fibroblasts filling the distal airways and alveoli, consistent with BOOP. In quantitative evaluation of BOOP using epithelial changes, inflammation and fibrosis were higher in ischemic left lungs than right or sham-operated left lungs. Apoptosis was increased in areas exhibiting histological BOOP, but there was no histological evidence of necrosis. Toll-like receptor 4 expression was increased in ischemic left lungs over right. An occlusive slipknot around the main left pulmonary artery in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP

Adaptive immunity to rhinoviruses: sex and age matter

Background: Rhinoviruses (RV) are key triggers in acute asthma exacerbations. Previous studies suggest that men suffer from infectious diseases more frequently and with greater severity than women. Additionally, the immune response to most infections and vaccinations decreases with age. Most immune function studies do not account for such differences, therefore the aim of this study was to determine if the immune response to rhinovirus varies with sex or age

Synthesis, Crystallographic Characterization and Density Functional Study of Novel Spoke-Molecular Tetravent ethyltriphenylphosphorous Dibromide

A novel molecular tetravent ethyltriphenylphosphorous dibromide ((C6H5) 3PCH2Br2) has been synthesized in toluene and has been characterized by single crystal x-ray crystallography. Theoretical studies have been conducted utilizing DFT (B3LYP/6-311+ G (d, p) level of theory both in gas phase and solution using diverse solvents. Potential surface energy calculations revealed the existence of the tetravelent diionic form as a global minimum except in dimethylsolfoxide where our adduct is more stable. Calculations showed that the Br-Br bond distance is in quadratic variation with the medium dielectric constant. The unusual Br-Br lengthen is reasonably rationalized in terms of charge transfer of electron density from the π clouds in phenyl moieties to the σ* of the dibromine entity. The average harmonic oscillator index of aromaticity of the complex are found suffering a deviation from unity

Early detection of pre-malignant lesions in a KRASG12D-driven mouse lung cancer model by monitoring circulating free DNA.

Lung cancer is the leading cause of cancer-related death. Two-thirds of cases are diagnosed at an advanced stage that is refractory to curative treatment. Therefore, strategies for the early detection of lung cancer are urgently sought. Total circulating free DNA (cfDNA) and tumour-derived circulating tumour DNA (ctDNA) are emerging as important biomarkers within a 'liquid biopsy' for monitoring human disease progression and response to therapy. Owing to the late clinical diagnosis of lung adenocarcinoma, the potential for cfDNA and ctDNA as early detection biomarkers remains unexplored. Here, using a Cre-regulated genetically engineered mouse model of lung adenocarcinoma development, driven by KrasG12D (the KrasLSL-G12D mouse), we serially tracked the release of cfDNA/ctDNA and compared this with tumour burden as determined by micro-computed tomography (CT). To monitor ctDNA, a droplet digital PCR assay was developed to permit discrimination of the KrasLox-G12D allele from the KrasLSL-G12D and KrasWT alleles. We show that micro-CT correlates with endpoint histology and is able to detect pre-malignant tumours with a combined volume larger than 7 mm3 Changes in cfDNA/ctDNA levels correlate with micro-CT measurements in longitudinal sampling and are able to monitor the emergence of lesions before the adenoma-adenocarcinoma transition. Potentially, this work has implications for the early detection of human lung adenocarcinoma using ctDNA/cfDNA profiling.A video abstract for this article is available at https://youtu.be/Ku8xJJyGs3UThis article has an associated First Person interview with the joint first authors of the paper.Medical Research Counci

Campus Vol IX N 4

Howard Studio. Cover. Picture. 1. Anonymous. Untitled. Prose. 4. Cook, Mike. misty Mood . Prose. 5. McIntosh, Bruce. Misty Mood . Picture. 5. Pritchard, Joen. In the Good \u27Ole Summertime... . Prose. 6. Stout, Prentice. In the Good \u27Ole Summertime... . Picture. 6. Hodges, John. How to Choose a Roommate . Prose. 7. Tuttle, C. Untitled. Cartoon. 7. Fenberg, Geo. M. Students--- . Prose. 3. Wood and Knapp. Jokes From the Jazz Age as Flips From Flappers . Prose. 8. Greenlee, Midge. Nine to Five . Prose. 10. Anonymous. Mr. and Miss Campus-1954 . Picture. 11. Anonymous. Well Shut My Mouth! . Prose. 14. Tuttle, C. Untitled. Cartoon. 14.; Miller, John. The Drums of Ku . Poem. 14. Hodge, Beth. About Face . Picture. 15. Rasor, Tip. Sports Calendar . Prose. 16. Anonymous. Senior Will . Prose. 18. Kull, Shaw. Untitled. Cartoon. 23

Shifting Teaching and Learning in Online Learning Spaces: An Investigation of a Faculty Online Teaching and Learning Initiative

We examined the adoption of online teaching strategies by faculty members at a large midwestern research university who participated in a year-long learning community. The purpose of this study was twofold: 1) to investigate changes in teaching approaches resulting from a year-long e-learning professional development initiative; and 2) to understand the perceptions of factors that influenced faculty members’ decision to adopt online or hybrid teaching approaches. The analysis was based on survey data and semi-structured interviews. Barriers, challenges, and successes to the adoption of online teaching strategies are also described in this article.

Identification of a novel class of autotaxin inhibitors through cross-screening

Three novel series were generated in order to mimic the pharmacophoric features displayed by lead compound AM095, a Lysophosphatidic acid (LPA1) receptor antagonist. Biological evaluation of this array of putative LPA1 antagonists led us to the discovery of three novel series of inhibitors of the ecto-enzyme Autotaxin (ATX), responsible for LPA production in blood, with potencies in the range 1 – 4 μM accompanied with good (> 100 μg/mL) solubility

Fungal diversity regulates plant-soil feedbacks in temperate grassland

Feedbacks between plants and soil microbial communities play an important role in vegetation dynamics, but the underlying mechanisms remain unresolved. Here, we show that the diversity of putative pathogenic, mycorrhizal, and saprotrophic fungi is a primary regulator of plant-soil feedbacks across a broad range of temperate grassland plant species. We show that plant species with resource-acquisitive traits, such as high shoot nitrogen concentrations and thin roots, attract diverse communities of putative fungal pathogens and specialist saprotrophs, and a lower diversity of mycorrhizal fungi, resulting in strong plant growth suppression on soil occupied by the same species. Moreover, soil properties modulate feedbacks with fertile soils, promoting antagonistic relationships between soil fungi and plants. This study advances our capacity to predict plant-soil feedbacks and vegetation dynamics by revealing fundamental links between soil properties, plant resource acquisition strategies, and the diversity of fungal guilds in soil