The potential to control Haemonchus contortus in indigenous South African goats with copper oxide wire particles

The high prevalence of resistance of Haemonchus contortus to all major anthelmintic groups has prompted investigations into alternative control methods in South Africa, including the use of copper oxide wire particle (COWP) boluses. To assess the efficacy of COWP against H. contortus in indigenous South African goats, 18 male faecal egg-count-negative goats were each given ca.1200 infective larvae of H. contortus three times per week during weeks 1 and 2 of the experiment. These animals made up an “established” infection group (ESTGRP). At the start of week 7, six goats were each given a 2-g COWP bolus orally; six goats received a 4-g COWP bolus each and six animals were not treated. A further 20 goats constituted a “developing” infection group (DEVGRP). At the beginning of week 1, seven of the DEVGRP goats were given a 2-g COWP bolus each; seven goats were treated with a 4-g COWP bolus each and no bolus was given to a further six animals. During weeks 1–6, each of these DEVGRP goats was given ca. 400 H. contortus larvae three times per week. All 38 goats were euthanized for worm recovery from the abomasa and small intestines in week 11. In the ESTGRP, the 2-g and 4-g COWP boluses reduced the worm burdens by 95% and 93%, respectively compared to controls (mean burden ± standard deviation, SD: 23 ± 33, 30 ± 56 and 442 ± 518 worms, P = 0.02). However, in the DEVGRP goats, both the 2-g and 4-g COWP treatments were ineffective in reducing the worm burdens relative to the controls (mean burdens ± SD: 1102 ± 841, 649 ± 855, 1051 ± 661 worms, P = 0.16). Mean liver copper levels did not differ between the ESTGRP goats treated with 2-g COWP, 4-g COWP or no COWP (mean ± standard error of the mean, SEM, in ppm: 93.7 ± 8.3; 101.5 ± 8.3; 71.8 ± 8.3, P = 0.07) nor did they differ between the DEVGRP goats (mean ± SEM, in ppm: 74.1 ± 9.1; 75.4 ± 9.1; 74.9 ± 10.0, P > 0.99). The copper values were considered adequate, but not high, for goats. The COWP boluses have the potential to be used in the place of conventional anthelmintics for the control of established H. contortus infections in indigenous South African goats, but their use as part of an integrated approach to control H. contortus in the field must be fully investigated

Persistence of the efficacy of copper oxide wire particles against Haemonchus contortus in grazing South African goats

A study was conducted to examine the duration of anthelmintic effect of copper oxide wire particles (COWP) in grazing goats, as data for the persistence of efficacy of COWP in this host species is limited. Forty-eight indigenous male goats were infected naturally by grazing them on Haemonchus contortus-infected pasture. When the faecal egg count (FEC) in the goats was 3179 ± 540 eggs per gram of faeces (mean ± standard error), half the animals were treated with 4 g COWP (day 0; mean live weight = 25.5 ± 0.8 kg). Eight treated (COWP) and eight non-treated (CONTROL) goats were removed from the pasture on each of days 7, 28 and 56, maintained for 27 or 29 days in concrete pens and then humanely slaughtered for nematode recovery. Mean liver copper levels were in the high range in the goats removed from pasture at day 7 (treated: 191 ± 19.7 ppm; untreated: 120 ± 19.7 ppm; P = 0.022), but had dropped to normal levels at days 28 and 56. The mean H. contortus burdens of the treated versus the non-treated goats were, respectively, 184 ± 48 and 645 ± 152 for the goats removed from pasture at day 7 (71% reduction; P = 0.004), 207 ± 42 and 331 ± 156 at day 28 (37% reduction; P = 0.945) and 336 ± 89 and 225 ± 53 at day 56 (−49% reduction; P = 0.665). Weekly monitoring of FECs after treatment until slaughter indicated that the COWP-treated goats had lower FECs than the controls, the treatment main effect being significant at days 7, 28 and 56 (P < 0.01). The day main effect and the treatment × day interaction were only significant for the goats removed from pasture at day 28 (P ≤ 0.001). Packed cell volumes increased during the course of the experiment (day, P < 0.001), but the treatment main effect was significant only for the goats removed from pasture at day 28 (CONTROL 28 d, 28.65 ± 0.52% < COWP 28 d, 31.31 ± 0.52%; P < 0.001). No differences in live weight between groups were considered to be of any practical significance. The study indicated that persistence of efficacy of COWP is limited in goats, extending at most to 28 days after treatment. However, repeated COWP administration at three-month intervals may be safe, given that liver copper levels return to normal two to three months after COWP treatment

Gravitational lensing as a contaminant of the gravity wave signal in CMB

Gravity waves (GW) in the early universe generate B-type polarization in the cosmic microwave background (CMB), which can be used as a direct way to measure the energy scale of inflation. Gravitational lensing contaminates the GW signal by converting the dominant E polarization into B polarization. By reconstructing the lensing potential from CMB itself one can decontaminate the B mode induced by lensing. We present results of numerical simulations of B mode delensing using quadratic and iterative maximum-likelihood lensing reconstruction methods as a function of detector noise and beam. In our simulations we find the quadratic method can reduce the lensing B noise power by up to a factor of 7, close to the no noise limit. In contrast, the iterative method shows significant improvements even at the lowest noise levels we tested. We demonstrate explicitly that with this method at least a factor of 40 noise power reduction in lensing induced B power is possible, suggesting that T/S=10^-6 may be achievable in the absence of sky cuts, foregrounds, and instrumental systematics. While we do not find any fundamental lower limit due to lensing, we find that for high-sensitivity detectors residual lensing noise dominates over the detector noise.Comment: 6 pages, 2 figures, submitted to PR

High-throughput screening of monoclonal antibodies against plant cell wall glycans by hierarchical clustering of their carbohydrate microarray binding profiles

Antibody-producing hybridoma cell lines were created following immunisation with a crude extract of cell wall polymers from the plant Arabidopsis thaliana. In order to rapidly screen the specificities of individual monoclonal antibodies (mAbs), their binding to microarrays containing 50 cell wall glycans immobilized on nitrocellulose was assessed. Hierarchical clustering of microarray binding profiles from newly produced mAbs, together with the profiles for mAbs with previously defined specificities allowed the rapid assignments of mAb binding to antigen classes. mAb specificities were further investigated using subsequent immunochemical and biochemical analyses and two novel mAbs are described in detail. mAb LM13 binds to an arabinanase-sensitive pectic epitope and mAb LM14, binds to an epitope occurring on arabinogalactan-proteins. Both mAbs display novel patterns of recognition of cell walls in plant materials

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.Peer reviewe

The Sudbury Neutrino Observatory

The Sudbury Neutrino Observatory is a second generation water Cherenkov detector designed to determine whether the currently observed solar neutrino deficit is a result of neutrino oscillations. The detector is unique in its use of D2O as a detection medium, permitting it to make a solar model-independent test of the neutrino oscillation hypothesis by comparison of the charged- and neutral-current interaction rates. In this paper the physical properties, construction, and preliminary operation of the Sudbury Neutrino Observatory are described. Data and predicted operating parameters are provided whenever possible.Comment: 58 pages, 12 figures, submitted to Nucl. Inst. Meth. Uses elsart and epsf style files. For additional information about SNO see http://www.sno.phy.queensu.ca . This version has some new reference

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism