Comparative Proteomic Analysis Of The Impact Of Management Programs On Porcine Airways

In North Carolina, swine are reared in confinement housing or pasture-based operations and air quality in confinement operations is known to contribute to health status. However, few if any reports investigate the impact of swine management operations on porcine airways; thus the goal of this project. The hypothesis was that airways of pigs reared indoors have morphological and proteome differences compared to pigs reared outdoors. Three experimental trials were conducted to observe airway morphology and proteomes. Trial I included three breed types raised indoors, Tamworth X Berkshire, Berkshire X Berkshire and Hertford X Berkshire (n = 4- 5 each). Trials II and III consisted of animals reared in both environments; Trial II had 28 pigs (n = 14 each, indoor and outdoor) and Trial III had 48 pigs (n = 24 each, indoor and outdoor). For Trial III, body weights were recorded weekly for seven weeks to adjust tracheal measure for body size. Two airway morphology features, total tracheal and lumen diameters, were recorded and compared in all trials. One-way and two-way analysis of variance (ANOVA) was performed and LSmeans with the PDiff Option was used to separate means as applicable. Outdoor animals had a larger variation of body weights than indoor animals; however, there was no correlation between tracheal measurements and body weight in this study. There was a difference in airway diameter and lumen among animals reared indoors versus outdoor (p-value \u3c 0.05); however, pens within housing type may have an effect. Comparative proteomics results suggest there are subtle differences among airway epithelia of animals reared indoors versus outdoors. Porcine airway epithelial cells exposed to swine confinement facility dust extract in vitro showed differential proteome modulation, including key inflammatory mediators cyclooxygenase-2 and inducible nitric oxide synthase. Taken together, these results demonstrate that there may be subtle differences between the impacts of the two hog management styles on porcine airway epithelial proteomes and morphology

Phenylephrine, a common cold remedy active ingredient, suppresses uterine contractions through cAMP signalling

Regulation of uterine contractility is an important aspect of women's health. Phenylephrine, a selective agonist of the α1-adrenoceptor and a potent smooth muscle constrictor, is widely used in women even during pregnancy to relieve cold-related symptoms, to treat postpartum haemorrhoid, and during routine eye exams. We performed isometric tension recordings to investigate the effect of phenylephrine on mouse uterine contractility. Phenylephrine decreased spontaneous and oxytocin-induced contractions in non-pregnant mouse uterine rings and strips with an IC50 of ~1 μM. Prazosin, an inhibitor of α1-adrenoceptor, did not prevent phenylephrine-mediated relaxations. Conversely, ICI118551, an antagonist of β2-adrenoceptors, inhibited phenylephrine relaxation. In the presence of ICI118551, high concentrations (>30 μM) of phenylephrine caused mouse uterine contractions, suggesting that β-adrenoceptor-mediated inhibition interferes with the phenylephrine contractile potential. Phenylephrine-dependent relaxation was reduced in the uterus of pregnant mice. We used primary mouse and human uterine smooth muscle cells (M/HUSMC) to establish the underlying mechanisms. Phenylephrine stimulated large increases in intracellular cAMP in M/HUSMCs. These cAMP transients were decreased when HUSMCs were cultured in the presence of oestrogen and progesterone to mimic the pregnancy milieu. Thus, phenylephrine is a strong relaxant in the non-pregnant mouse uterus, but exhibits diminished effect in the pregnant uterus

Technical Design Report for the PANDA Micro Vertex Detector

This document illustrates the technical layout and the expected performance of the Micro Vertex Detector (MVD) of the PANDA experiment. The MVD will detect charged particles as close as possible to the interaction zone. Design criteria and the optimisation process as well as the technical solutions chosen are discussed and the results of this process are subjected to extensive Monte Carlo physics studies. The route towards realisation of the detector is outlined

Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress

WOS: 000374502300001PubMed ID: 27143852Background: Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs) are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression. Methods: Rat VSMCs were stimulated by PDGF (50 ng/mL) plus TNF-alpha (10 ng/mL) or left unstimulated for a further 24 hours in serum-free medium. In other series of experiments, cells were pre-treated either with SC-514 (50 mu M) or with apocynin (20 nM) for 2 hours, then zoledronate (100 mu M) was added into 2% fetal calf serum containing medium for 24 hours. Results and discussion: Using isolated rat VSMCs in culture, zoledronate (100 mu M) increased MMP-9 and -13 mRNA expressions but inhibited MMP-2 expression. MMP-9 and MMP-13 up-regulation was shown to depend on the NF-kappa B pathway; and this was activated by zoledronate. Furthermore, zoledronate elevated the levels of reactive oxygen species detected by either dichlorofluorescein in isolated VSMCs or lucigenin enhanced chemiluminescence in rat aortic rings in vitro. Apocynin, an inhibitor of NADPH oxidase, reversed NF-kappa B activation and MMP-9 and MMP-13 up-regulation by zoledronate. Conclusion: We conclude that zoledronate increases MMP-9 and MMP-13 expressions in rat VSMCs dependent upon stimulation of the NF-kappa B pathway by reactive oxygen species. Effects on MMP expression may contribute to the pharmacologic profile of bisphosphonates.British Heart FoundationBritish Heart Foundation [CH95/001]; British Heart FoundationBritish Heart Foundation [RG/09/006/27918]The authors would like to thank Dr Goksel Gokce, Ege University Faculty of Pharmacy and Dr Steve White, University of Bristol for valuable help and expertise on oxidative stress measurements. MZA would also like to thank Prof Levent Ustunes for kind help and encouragement. This study was supported by the British Heart Foundation grant CH95/001

The clonal root system of balsam poplar in upland sites of Quebec and Alberta

Balsam poplar seeds are short-lived and require moist seedbeds soon after they are released to germinate. In addition to sexual reproduction, balsam poplar stands can regenerate clonally by root suckering. The origin of stands will in turn affect their genetic structure and root system architecture, which are poorly understood for upland forest stands. Three stands were hydraulically excavated in Quebec (moist) and Alberta (dry) to determine the origin of trees and to characterize root systems with respect to presence of parental roots and root grafts connections. Clones were identified using single-nucleotide polymorphism (SNPs), and all stems, roots and root grafts were aged using dendrochronology techniques. All 82 excavated trees were of sucker origin, and four of the six stands contained a single clone. Parental root connections were found between 22% and 25% of excavated trees, and 53% and 48% of trees were linked with a root graft between the same or different clones, in Alberta and Quebec, respectively. Mean distance between trees connected by parental root was significantly lower than the distance between unconnected trees (0.47 ± 0.25 m vs. 3.14 ± 0.15 m and 1.55 ± 0.27 m vs. 4.25 ± 0.13 m) in Alberta and in Quebec, respectively. The excavations also revealed many dead stumps with live roots, maintained through root connections with live trees. This research highlights that balsam poplar growing in upland stands is a clonal species that can maintain relatively high genotypic diversity, with frequent root connections between trees at maturity. Maintaining an extensive root system through root connections increases the chances of a clone surviving when the above ground tree is dead and may also enhance the resilience of balsam poplar stands after disturbance

Towards Real Time Characterization of Grain Growth from the Melt

Single crystal materials have unique properties which are endowed by their long ranging atomic order. Growing these crystalline materials can be difficult, as entropy favors disordered grains. The optical floating zone furnace provides an efficient way to make novel single crystal materials, enabling the study of crystals with complex chemical makeup which other techniques would not be able to provide. However, the growth mechanisms of these crystals is poorly understood, leaving the process of making them prone to trial and error and limiting its application in the broader research community. This work aims to understand the microstructural dynamics of floating zone growth using x-ray scattering techniques. These techniques include x-ray diffraction tomography and two dimensional crystal mapping. One focus of this work is building the computational infrastructure to process the large stream of heterogeneous data which results from these techniques. Additionally, this work includes computational and experimental commissioning of the x-ray diffraction tomography technique, helping to understand the advantages and limitations of the current approaches. These pieces of infrastructure are then used to characterize the growth of Rutile crystals via a float zone furnace. Particular attention is paid to the competition amongst the grains, and how certain grains are selected from the plethora which are created at the beginning of the growth

A new family of covalent inhibitors block nucleotide binding to the active site of pyruvate kinase

PYK (pyruvate kinase) plays a central role in the metabolism of many organisms and cell types, but the elucidation of the details of its function in a systems biology context has been hampered by the lack of specific high-affinity small-molecule inhibitors. High-throughput screening has been used to identify a family of saccharin derivatives which inhibit LmPYK (Leishmania mexicana PYK) activity in a time- (and dose-) dependent manner, a characteristic of irreversible inhibition. The crystal structure of DBS {4-[(1,1-dioxo-1,2-benzothiazol-3-yl)sulfanyl]benzoic acid} complexed with LmPYK shows that the saccharin moiety reacts with an active-site lysine residue (Lys335), forming a covalent bond and sterically hindering the binding of ADP/ATP. Mutation of the lysine residue to an arginine residue eliminated the effect of the inhibitor molecule, providing confirmation of the proposed inhibitor mechanism. This lysine residue is conserved in the active sites of the four human PYK isoenzymes, which were also found to be irreversibly inhibited by DBS. X-ray structures of PYK isoforms show structural differences at the DBS-binding pocket, and this covalent inhibitor of PYK provides a chemical scaffold for the design of new families of potentially isoform-specific irreversible inhibitors

Spartan Daily, February 13, 1975

Volume 64, Issue 9https://scholarworks.sjsu.edu/spartandaily/5942/thumbnail.jp