The effect of Cichorium intybus and Lotus corniculatus on nematode burdens and production in grazed lambs

This report was presented at the UK Organic Research 2002 Conference. The study was designed to examine the hypothesis that chicory (Cichorium intybus) and Lotus sp. (Lotus corniculatus) have the potential to affect the naturally acquired nematode burden in grazed lambs. Organic male castrate lambs (48) with a naturally acquired parasite burden grazed replicate combination plots (0.6 ha) of chicory, Lotus corniculatus, perennial ryegrass (Lolium perenne) and white clover (Trifolium repens). Lamb performance was determined by weekly weight gain and condition score assessments. Nematode burden was assessed by individual lamb faecal egg count (FEC) before and after drenching (levamisole). The range of parasitic helminths present was assessed by faecal culture and by total worm counts performed on a proportion of the lambs at slaughter. Weekly pasture larval counts (PLCs) were conducted on the trial plots. A concurrent small plot study (6 x 1m2 replicates) of each of the forages used in the grazing trial was run to assess the potential effect of forage type on the development and survival of Teladorsagia circumcincta assessed by weekly PLCs. Preliminary data suggest that lambs grazing chicory or a combination of lotus and chicory had lower FECs than those grazing PRG/WC, however there was no significant difference in the total worm counts

Incorporating Uncertainties in Atomic Data Into the Analysis of Solar and Stellar Observations: A Case Study in Fe XIII

Information about the physical properties of astrophysical objects cannot be measured directly but is inferred by interpreting spectroscopic observations in the context of atomic physics calculations. Ratios of emission lines, for example, can be used to infer the electron density of the emitting plasma. Similarly, the relative intensities of emission lines formed over a wide range of temperatures yield information on the temperature structure. A critical component of this analysis is understanding how uncertainties in the underlying atomic physics propagates to the uncertainties in the inferred plasma parameters. At present, however, atomic physics databases do not include uncertainties on the atomic parameters and there is no established methodology for using them even if they did. In this paper we develop simple models for the uncertainties in the collision strengths and decay rates for Fe XIII and apply them to the interpretation of density sensitive lines observed with the EUV Imagining spectrometer (EIS) on Hinode. We incorporate these uncertainties in a Bayesian framework. We consider both a pragmatic Bayesian method where the atomic physics information is unaffected by the observed data, and a fully Bayesian method where the data can be used to probe the physics. The former generally increases the uncertainty in the inferred density by about a factor of 5 compared with models that incorporate only statistical uncertainties. The latter reduces the uncertainties on the inferred densities, but identifies areas of possible systematic problems with either the atomic physics or the observed intensities.Comment: in press at Ap

Cardiovascular Magnetic Resonance Imaging of Scar Development Following Pulmonary Vein Isolation: A Prospective Study

Aims Cardiovascular magnetic resonance (MR) provides non-invasive assessment of early (24-hour) edema and injury following pulmonary vein isolation (by ablation) and subsequent scar formation. We hypothesize that 24-hours after ablation, cardiovascular MR would demonstrate a pattern of edema and injury due to ablation and the severity would correlate with subsequent scar. Methods: Fifteen atrial fibrillation patients underwent cardiovascular MR prior to pulmonary vein isolation, 24-hours post (N = 11) and 30-days post (N = 7) ablation, with T2-weighted (T2W) and late gadolinium enhancement (LGE) imaging. Left atrial wall thickness, edema enhancement ratio and LGE enhancement were assessed at each time point. Volumes of LGE and edema enhancement were measured, and the circumferential presence of injury was assessed at 24-hours, including comparison with LGE enhancement at 30 days. Results: Left atrial wall thickness was increased 24-hours post-ablation (10.7±4.1 mm vs. 7.0±1.8 mm pre-PVI, p<0.05). T2W enhancement at 24-hours showed increased edema enhancement ratio (1.5±0.4 for post-ablation, vs. 0.9±0.2 pre-ablation, p<0.001). Edema and LGE volumes at 24-hours were correlated with 30-day LGE volume (R = 0.76, p = 0.04, and R = 0.74, p = 0.09, respectively). Using a 16 segment model for assessment, 24-hour T2W had sensitivity, specificity, and accuracy of 82%, 63%, and 79% respectively, for predicting 30-day LGE. 24-hour LGE had sensitivity, specificity, and accuracy of 91%, 47%, and 84%. Conclusions: Increased left atrial wall thickening and edema were characterized on cardiovascular MR early post-ablation, and found to correlate with 30-day LGE scar

Phenylbutyric Acid Rescues Endoplasmic Reticulum Stress-Induced Suppression of APP Proteolysis and Prevents Apoptosis in Neuronal Cells

BACKGROUND: The familial and sporadic forms of Alzheimer's disease (AD) have an identical pathology with a severe disparity in the time of onset [1]. The pathological similarity suggests that epigenetic processes may phenocopy the Familial Alzheimer's disease (FAD) mutations within sporadic AD. Numerous groups have demonstrated that FAD mutations in presenilin result in 'loss of function' of gamma-secretase mediated APP cleavage [2], [3], [4], [5]. Accordingly, ER stress is prominent within the pathologically impacted brain regions in AD patients [6] and is reported to inhibit APP trafficking through the secretory pathway [7], [8]. As the maturation of APP and the cleaving secretases requires trafficking through the secretory pathway [9], [10], [11], we hypothesized that ER stress may block trafficking requisite for normal levels of APP cleavage and that the small molecular chaperone 4-phenylbutyrate (PBA) may rescue the proteolytic deficit. METHODOLOGY/PRINCIPAL FINDINGS: The APP-Gal4VP16/Gal4-reporter screen was stably incorporated into neuroblastoma cells in order to assay gamma-secretase mediated APP proteolysis under normal and pharmacologically induced ER stress conditions. Three unrelated pharmacological agents (tunicamycin, thapsigargin and brefeldin A) all repressed APP proteolysis in parallel with activation of unfolded protein response (UPR) signaling-a biochemical marker of ER stress. Co-treatment of the gamma-secretase reporter cells with PBA blocked the repressive effects of tunicamycin and thapsigargin upon APP proteolysis, UPR activation, and apoptosis. In unstressed cells, PBA stimulated gamma-secretase mediated cleavage of APP by 8-10 fold, in the absence of any significant effects upon amyloid production, by promoting APP trafficking through the secretory pathway and the stimulation of the non-pathogenic alpha/gamma-cleavage. CONCLUSIONS/SIGNIFICANCE: ER stress represses gamma-secretase mediated APP proteolysis, which replicates some of the proteolytic deficits associated with the FAD mutations. The small molecular chaperone PBA can reverse ER stress induced effects upon APP proteolysis, trafficking and cellular viability. Pharmaceutical agents, such as PBA, that stimulate alpha/gamma-cleavage of APP by modifying intracellular trafficking should be explored as AD therapeutics

Coyote, Canis latrans - Rio Grande Turkey, Meleagris gallopavo intermedia, Interactions

Coyotes (Canis latrans) are widely known to be predators of Wild Turkeys (Meleagris gallopauo sspp.). We describe two observations of single Coyotes coming within 10 m of feeding Wild Turkey flocks without attempting to predate them in Stevens County, Kansas. We relate these observations to Coyote predation on turkeys and mobbing behavior

Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation

<p>Abstract</p> <p>Background</p> <p>Intestinal barrier function is important for preserving health, as a compromised barrier allows antigen entry and can induce inflammatory diseases. Probiotic bacteria can play a role in enhancing intestinal barrier function; however, the mechanisms are not fully understood. Existing studies have focused on the ability of probiotics to prevent alterations to tight junctions in disease models, and have been restricted to a few tight junction bridging proteins. No studies have previously investigated the effect of probiotic bacteria on healthy intestinal epithelial cell genes involved in the whole tight junction signalling pathway, including those encoding for bridging, plaque and dual location tight junction proteins. Alteration of tight junction signalling in healthy humans is a potential mechanism that could lead to the strengthening of the intestinal barrier, resulting in limiting the ability of antigens to enter the body and potentially triggering undesirable immune responses.</p> <p>Results</p> <p>The effect of <it>Lactobacillus plantarum </it>MB452 on tight junction integrity was determined by measuring trans-epithelial electrical resistance (TEER) across Caco-2 cell layers. <it>L. plantarum </it>MB452 caused a dose-dependent TEER increase across Caco-2 cell monolayers compared to control medium. Gene expression was compared in Caco-2 cells untreated or treated with <it>L. plantarum </it>MB452 for 10 hours. Caco-2 cell RNA was hybridised to human oligonucleotide arrays. Data was analysed using linear models and differently expressed genes were examined using pathway analysis tools. Nineteen tight junction-related genes had altered expression levels in response to <it>L. plantarum </it>MB452 (modified-P < 0.05, fold-change > 1.2), including those encoding occludin and its associated plaque proteins that anchor it to the cytoskeleton. <it>L. plantarum </it>MB452 also caused changes in tubulin and proteasome gene expression levels which may be linked to intestinal barrier function. Caco-2 tight junctions were visualised by fluorescent microscopy of immuno-stained occludin, zona occludens (ZO)-1, ZO-2 and cingulin. Caco-2 cells treated with <it>L. plantarum </it>MB452 had higher intensity fluorescence of each of the four tight junction proteins compared to untreated controls.</p> <p>Conclusions</p> <p>This research indicates that enhancing the expression of genes involved in tight junction signalling is a possible mechanism by which <it>L. plantarum </it>MB452 improves intestinal barrier function.</p

A Method for Data-Driven Simulations of Evolving Solar Active Regions

We present a method for performing data-driven simulations of solar active region formation and evolution. The approach is based on magnetofriction, which evolves the induction equation assuming the plasma velocity is proportional to the Lorentz force. The simulations of active region coronal field are driven by temporal sequences of photospheric magnetograms from the Helioseismic Magnetic Imager (HMI) instrument onboard the Solar Dynamics Observatory (SDO). Under certain conditions, the data-driven simulations produce flux ropes that are ejected from the modeled active region due to loss of equilibrium. Following the ejection of flux ropes, we find an enhancement of the photospheric horizontal field near the polarity inversion line. We also present a method for the synthesis of mock coronal images based on a proxy emissivity calculated from the current density distribution in the model. This method yields mock coronal images that are somewhat reminiscent of images of active regions taken by instruments such as SDO's Atmospheric Imaging Assembly (AIA) at extreme ultraviolet wavelengths.Comment: Accepted to ApJ; comments/questions related to this article are welcome via e-mail, even after publicatio

Highly stable fullerene-based porous molecular crystals with open metal sites

The synthesis of conventional porous crystals involves building a framework using reversible chemical bond formation, which can result in hydrolytic instability. In contrast, porous molecular crystals assemble using only weak intermolecular interactions, which generally do not provide the same environmental stability. Here, we report that the simple co-crystallization of a phthalocyanine derivative and a fullerene (C60 or C70) forms porous molecular crystals with environmental stability towards high temperature and hot aqueous base or acid. Moreover, by using diamond anvil cells and synchrotron single-crystal measurements, stability towards extreme pressure (>4 GPa) is demonstrated, with the stabilizing fullerene held between two phthalocyanines and the hold tightening at high pressure. Access to open metal centres within the porous molecular co-crystal is demonstrated by in situ crystallographic analysis of the chemisorption of pyridine, oxygen and carbon monoxide. This suggests strategies for the formation of highly stable and potentially functional porous materials using only weak van der Waals intermolecular interactions

A Study of Thymidylate Synthase Expression as a Biomarker for Resectable Colon Cancer: Alliance (Cancer and Leukemia Group B) 9581 and 89803.

PurposeTumor levels of thymidylate synthase (TS), a target of 5-fluorouracil (5-FU)-based chemotherapy for colorectal cancer, have been studied as a predictive or prognostic biomarker with mixed results.Patients and methodsTumor TS levels were prospectively evaluated in two adjuvant therapy trials for patients with resected stage II or III colon cancer. TS expression was determined by standard immunohistochemistry and by automated quantitative analysis. Tumor mismatch repair deficiency (MMR-D) and BRAF c.1799T &gt; A (p.V600E) mutation status were also examined. Relationships between tumor TS, MMR-D, and BRAF mutation status, overall survival (OS), and disease-free survival (DFS) were investigated in the subset of stage III patients.ResultsPatients whose tumors demonstrated high TS expression experienced better treatment outcomes, with DFS hazard ratio (HR) = 0.67, 95% confidence interval (CI) = 0.53, 0.84; and OS HR = 0.68, 95% CI = 0.53, 0.88, for high versus low TS expression, respectively. No significant interaction between TS expression and stage was observed (DFS: interaction HR = 0.94; OS: interaction HR = 0.94). Tumors with high TS expression were more likely to demonstrate MMR-D (22.2% vs. 12.8%; p =  .0003). Patients whose tumors demonstrated both high TS and MMR-D had a 7-year DFS of 77%, compared with 58% for those whose tumors had low TS and were non-MMR-D (log-rank p =  .0006). Tumor TS expression did not predict benefit of a particular therapeutic regimen.ConclusionThis large prospective analysis showed that high tumor TS levels were associated with improved DFS and OS following adjuvant therapy for colon cancer, although tumor TS expression did not predict benefit of 5-FU-based chemotherapy. The Oncologist 2017;22:107-114Implications for Practice: This study finds that measurement of tumor levels of thymidylate synthase is not helpful in assigning specific adjuvant treatment for colorectal cancer. It also highlights the importance of using prospective analyses within treatment clinical trials as the optimal method of determining biomarker utility