The presence of in-feed anti-sea lice drugs and their relationship with organic enrichment is poorly understood in sediment surrounding salmon farms. Using data from an aquaculture monitoring program ...(2018–2020), we describe this relationship at ten sites in four Canadian provinces. Three anti-sea lice pesticides (lufenuron, teflubenzuron, emamectin benzoate and metabolite desmethyl emamectin benzoate), and one antibiotic (oxytetracycline) were detected. Concentrations were often below limits of quantification. Values are also lower than those reported in other aquaculture salmon-producing countries. Highest concentrations, along with organic enrichment, were observed ~200 m of cages with lower concentrations detected up to 1.5 km away. Most samples had at least two drugs present: 75.2 % (British Columbia), 91.4 % (Newfoundland), and 54.8 % (New Brunswick/Nova Scotia) highlighting the potential for cumulative effects. Emamectin benzoate and oxytetracycline were detected four and three years respectively after last known treatments, demonstrating the need for research on overall persistence of compounds.
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•Sediment data collected through an aquaculture monitoring program were used.•Three anti-sea lice drugs and one antibiotic were detected at ten salmon sites.•The highest concentrations and organic enrichment were observed within 200 m of cages.•Most sediment samples had at least two drugs present.•There is a significant patchiness in drug presence and organic matter enrichment.
Several trace-elements have been identified as indicators of finfish aquaculture organic enrichment. In this study, sediment sampling at finfish farms was completed as part of an Aquaculture ...Monitoring Program in three distinct Canadian regions. Despite diverse datasets, multivariate analyses show a consistent clustering of known direct (Cu and Zn) and indirect (Cd, Mo and U) tracers of aquaculture activities with sediment organic matter (OM) and/or total dissolved sulfides concentrations. OM content was also a predictor of Cu, Zn, Mo and U concentrations according to decision tree analyses. Distance from cages did not emerge as a strong driver of differences among sampling points; however, a tendency towards negative associations is clear especially for Zn. Enriched stations as determined after geochemical normalization were mostly localized within 150 m of net-pens. Selected trace-elements (in particular Zn) can be useful indicators of aquaculture organic enrichment in different ecosystems and valuable tools for monitoring programs.
•Sediment sampling at finfish farms was completed in three distinct Canadian regions.•Multivariate analyses show a clustering of Cu, Zn, Cd, Mo and U with sediment organic matter and/or total dissolved sulfides.•Organic matter content is a predictor of Cu, Zn, Mo and U concentrations as per decision tree analyses.•Enriched stations in selected trace-metals were localized within 150 m of net-pens.•Selected trace-elements (in particular Zn) are useful indicators of aquaculture organic enrichment.
Germ-line mutations in CYLD are found in patients with familial skin appendage tumours. The protein product functions as a deubiquitinase enzyme, which negatively regulates NF-kappaB and c-Jun ...N-terminal kinase signalling. Brooke-Spiegler syndrome (BSS) is characterised by cylindromas, trichoepitheliomas and spiradenomas, whereas in familial cylindromatosis (FC) patients present with cylindromas and in multiple familial trichoepitheliomas (MFT) with trichoepitheliomas as the only skin tumour type. Although described as distinct entities, recent studies suggest that they are within the spectrum of a single entity.
To investigate the mutation spectrum of CYLD and possible genotype-phenotype correlations.
25 families including 13 BSS, 3 FC, and 9 MFT families were examined and evaluated for mutations in the CYLD gene.
In total, 18 mutations in CYLD, including 6 novel mutations, were identified in 25 probands (72%). The mutation frequencies among distinct phenotypes were 85% for BSS, 100% for FC, and 44% for MFT. The majority of the mutations were insertions, deletions or nonsense mutations leading to formation of truncated proteins. All mutations were located between exons 9 to 20, encoding the NEMO binding site and the catalytic domain. Genotype-phenotype analysis failed to reveal a correlation between the types of mutations and their location within the gene and the patients' phenotypes and disease severity.
This study provides further evidence on the role of CYLD in the pathogenesis of skin appendage tumours characterised by cylindromas, trichoepitheliomas and/or spiradenomas, but the molecular mechanisms of CYLD in skin tumorigenesis and the reasons for phenotypic variability remain to be explored.
The expressions of 78 protein kinases, 24 protein phosphatases and 31 phosphoproteins were investigated by Kinetworks™ analysis in brain and spinal cord tissue of transgenic mice over‐expressing G93A ...mutant superoxide dismutase (mSOD), a murine model of amyotrophic lateral sclerosis (ALS). In the brains of affected mSOD mice, we observed increased expression of cAMP‐dependent protein kinase (PKA, 111% increase compared with control), and protein phosphatase 2B Aα‐catalytic subunit (calcineurin, 109% increase), and reductions in the levels of PAK3 (76% decrease) and protein phosphatase 2C Cβ‐subunit (32% decrease). Increased Ser259 phosphorylation of Raf1 (126% increase) in mSOD mice correlated with higher expression of p73 Raf1 (147% increase). There was also increased p73 Raf1 (69% increase) and Ser259 phosphorylation (45% increase) in the spinal cords of mSOD mice. While adducin underwent enhanced phosphorylation (αS724, 90% increase; γS662, 290% increase) in mSOD brain, its phosphorylation was lower in the mSOD spinal cord (αS724, 53% decrease; γS662, 46% decrease). In spinal cords of affected mSOD mice, we also observed elevated expression of casein kinase 1δ (CK1δ, 157% increase), JAK2 (84% increase), PKA (183% increase), protein kinase C (PKC) δ (123% increase), p124 PKCµ (142% increase), and RhoA kinase (221% increase), and enhanced phosphorylation of extracellular regulated kinases 1 (ERK1, T202/Y204, 90% increase), and 2 (ERK2, T185/Y187, 73% increase), p38 MAP kinase (T180/Y182, 1570% increase), and PKBα (T308, 154% increase; S473, 61% increase). There was also reduced phosphorylation of RB (S780, 45% decrease; S807/S811, 65% decrease), Src (Y418, 63% decrease) and p40 SAPK/JNKβ (T183/Y185, 43% decrease). Variability in the expression of kinases, phosphatases and phosphorylation of their substrates was observed even in mutant animals having a similar phenotype. The expression and phosphorylation differences between mSOD and control mice were dissimilar to those between ALS patients and controls. This finding indicates that the activation of protein kinases and phosphoproteins is different with neuron loss in the mSOD mouse compared with that seen in patients with the sporadic form of ALS.
Metastatic melanoma is a disease with a poor prognosis that currently lacks effective treatments. Critical biological features of metastasis include acquisition of migratory competence, growth factor ...independence, and invasive potential. In an attempt to identify genes that contribute to melanoma pathogenesis, a genome-wide search using bacterial artificial chromosome array comparative genomic hybridization and single nucleotide polymorphism arrays in a series of 64 metastatic melanoma samples and 20 melanoma cell lines identified increased copy numbers of Gab2 located on 11q14.1. Gab2 is an adaptor protein that potentiates the activation of the Ras-Erk and PI3K-Akt pathways and has recently been implicated in human cancer; however, its role in melanoma has not been explored. In this study, we found that Gab2 was either amplified (∼11%) and/or overexpressed (∼50%) in melanoma. Gab2 protein expression correlated with clinical melanoma progression, and higher levels of expression were seen in metastatic melanomas compared with primary melanoma and melanocytic nevi. We found that overexpression of Gab2 potentiates, whereas silencing of Gab2 reduces, migration and invasion of melanoma cells. Gab2 mediated the hyperactivation of Akt signaling in the absence of growth factors, whereas inhibition of the PI3K-Akt pathway decreased Gab2-mediated tumor cell migration and invasive potential. Gab2 overexpression resulted in enhanced tumor growth and metastatic potential in vivo . These studies demonstrate a previously undefined role for Gab2 in melanoma tumor progression and metastasis.
This paper presents an approach for computing global distance metrics that minimize the k-NN leave-one-out (LOO) error. The approach optimizes an energy function that corresponds to a smoothened ...version of the k-NN LOO error. The generalization of the proposed approach is further improved by controlling the k parameter through a heuristic. Evaluation of the proposed approach on several public datasets showed that it was able to compete with an established state-of-the art approach.
We describe the simulated data sample for the Photometric Large Synoptic Survey Telescope (LSST) Astronomical Time Series Classification Challenge (PLAsTiCC), a publicly available challenge to ...classify transient and variable events that will be observed by the LSST, a new facility expected to start in the early 2020s. The challenge was hosted by Kaggle, ran from 2018 September 28 to December 17, and included 1094 teams competing for prizes. Here we provide details of the 18 transient and variable source models, which were not revealed until after the challenge, and release the model libraries at https://doi.org/10.5281/zenodo.2612896. We describe the LSST Operations Simulator used to predict realistic observing conditions, and we describe the publicly available SNANA simulation code used to transform the models into observed fluxes and uncertainties in the LSST passbands (ugrizy). Although PLAsTiCC has finished, the publicly available models and simulation tools are being used within the astronomy community to further improve classification, and to study contamination in photometrically identified samples of SN Ia used to measure properties of dark energy. Our simulation framework will continue serving as a platform to improve the PLAsTiCC models, and to develop new models.
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