Neutral genetic variation in adult Chinook salmon (Oncorhynchus tshawytscha) affects brain-to-body trade-off and brain laterality

Low levels of heterozygosity can have detrimental effects on life history and growth characteristics of organisms but more subtle effects such as those on trade-offs of expensive tissues and morphological laterality, especially of the brain, have not been explicitly tested. The objective of the current study was to investigate how estimated differences in heterozygosity may potentially affect brain-to-body trade-offs and to explore how these heterozygosity differences may affect differential brain growth, focusing on directional asymmetry in adult Chinook salmon (Oncorhynchus tshawytscha) using the laterality and absolute laterality indices. Level of inbreeding was estimated as mean microsatellite heterozygosity resulting in four ‘inbreeding level groups’ (Very High, High, Medium, Low). A higher inbreeding level corresponded with a decreased brain-to-body ratio, thus a decrease in investment in brain tissue, and also showed a decrease in the laterality index for the cerebellum, where the left hemisphere was larger than the right across all groups. These results begin to show the role that differences in heterozygosity may play in differential tissue investment and in morphological laterality, and may be useful in two ways. Firstly, the results may be valuable for restocking programmes that wish to emphasize brain or body growth when crossing adults to generate individuals for release, as we show that genetic variation does affect these trade-offs. Secondly, this study is one of the first examinations to test the hypothesized relationship between genetic variation and laterality, finding that in Chinook salmon there is potential for an effect of inbreeding on lateralized morphology, but not in the expected direction

Germline Maintenance Through the Multifaceted Activities of GLH/Vasa in

Vasa homologs are ATP-dependent DEAD-box helicases, multipotency factors, and critical components that specify and protect the germline. They regulate translation, amplify piwi-interacting RNAs (piRNAs), and act as RNA solvents; however, the limited availability of mutagenesis-derived alleles and their wide range of phenotypes have complicated their analysis. Now, with clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), these limitations can be mitigated to determine why protein domains have been lost or retained throughout evolution. Here, we define the functional motifs of GLH-1/Vasa i

Extracellular dsRNA induces a type I interferon response mediated via class A scavenger receptors in a novel Chinook salmon derived spleen cell line

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.dci.2018.08.010 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Despite increased global interest in Chinook salmon aquaculture, little is known of their viral immune defenses. This study describes the establishment and characterization of a continuous cell line derived from Chinook salmon spleen, CHSS, and its use in innate immune studies. Optimal growth was seen at 14–18 °C when grown in Leibovitz's L-15 media with 20% fetal bovine serum. DNA analyses confirmed that CHSS was Chinook salmon and genetically different from the only other available Chinook salmon cell line, CHSE-214. Unlike CHSE-214, CHSS could bind extracellular dsRNA, resulting in the rapid and robust expression of antiviral genes. Receptor/ligand blocking assays confirmed that class A scavenger receptors (SR-A) facilitated dsRNA binding and subsequent gene expression. Although both cell lines expressed three SR-A genes: SCARA3, SCARA4, and SCARA5, only CHSS appeared to have functional cell-surface SR-As for dsRNA. Collectively, CHSS is an excellent cell model to study dsRNA-mediated innate immunity in Chinook salmon.Natural Sciences and Engineering Research Council of CanadaCanada Research Counci

Isotopic and Compositional Variations in Single Nuclear Fuel Pellet Particles Analyzed by Nanoscale Secondary Ion Mass Spectrometry

Article published under an ACS AuthorChoice LicenseThe Collaborative Materials Exercise (CMX) is organized by the Nuclear Forensics International Technical Working Group, with the aim of advancing the analytical capabilities of the participating organizations and providing feedback on the best approaches to a nuclear forensic investigation. Here, model nuclear fuel materials from the 5th CMX iteration were analyzed using a NanoSIMS 50L (CAMECA) in order to examine inhomogeneities in the U-235/U-238 ratio and trace element abundance within individual, micrometer scale particles. Two fuel pellets were manufactured for the exercise and labelled CMX-5A and CMX-5B. These pellets were created using different processing techniques, but both had a target enrichment value of U-235/U-238 = 0.01. Particles from these pellets were isolated for isotopic and trace element analysis. Fifteen CMX-5A particles and 20 CMX-5B particles were analyzed, with both sample types displaying inhomogeneities in the U isotopic composition at a sub-micrometer scale within individual particles. Typical particle diameters were similar to 1.5 to 41 mu m for CMX-5A and similar to 1 to 61 mu m for CMX-5B. The CMX-5A particles were shown to be more isotopically homogeneous, with a mean U-235/U-238 atom ratio of 0.0130 +/- 0.0066. The CMX-5B particles showed a predominantly depleted mean U-235/U-238 atom ratio of 0.0063 +/- 0.0094, which is significantly different to the target enrichment value of the pellet and highlights the potential variation of U-235/U-238 in U fuel pellets at the micrometer scale. This study details the successful application of the NanoSIMS 50L in a mock nuclear forensic investigation by optimizing high-resolution imaging for uranium isotopics.Peer reviewe

Labour market experiences of young UK Bangladeshi men: Identity, inclusion and exclusion in inner-city London

Detailed qualitative data are used to explore the processes perpetuatinglabour market disadvantage among young UK-Bangladeshi men living in central London. Strong forces of inclusion within the Bangladeshi community are found to interact with forces of exclusion from ‘mainstream’ society to constrain aspirations and limit opportunities. Though diverse forms of young Bangladeshi masculinity are found, a common pattern is heavy dependency on intra-ethnic networks. Negative experiences of and isolation from ‘mainstream’ society further reinforce reliance on ‘our own people’. However, acute ambivalence towards belonging to a dense Bangladeshi community exists, exemplified in the widespread denigration of the restaurant trade. Many respondents express the desire to ‘break out’ and access new experiences. The findings support current policy emphasis on ‘connecting people to work’ but highlight the more fundamental need to connect people across ethnic boundaries. The paper urges researchers to ‘unpack’ ethnicity to consider carefully what ethnic identity implies in terms of access to resources and opportunities for different individuals in different contexts in order better to understand the diversity of labour market outcomes and the persistence of disadvantage

Binding loci of RelA-containing nuclear factor-kappaB dimers in promoter regions of PHM1-31 myometrial smooth muscle cells.

Human parturition is associated with many pro-inflammatory mediators which are regulated by the nuclear factor-kappaB (NF-κB) family of transcription factors. In the present study, we employed a ChIP-on-chip approach to define genomic loci within chromatin of PHM1-31 myometrial cells that were occupied by RelA-containing NF-κB dimers in response to a TNF stimulation of 1 h. In TNF-stimulated PHM1-31 cells, anti-RelA serum enriched 13 300 chromatin regions; importantly, 11 110 regions were also enriched by anti-RelA antibodies in the absence of TNF. DNA sequences in these regions, from both unstimulated or TNF-stimulated PHM1-31 cultures, were associated with genic regions including IκBα, COX-2, IL6RN, Jun and KCNMB3. TNF-induced binding events at a consensus κB site numbered 1667; these were represented by 112 different instances of the consensus κB motif. Of the 1667 consensus κB motif occurrences, 770 (46.2%) were identified within intronic regions. In unstimulated PHM1-31 cells, anti-RelA-serum-enriched regions were associated with sequences corresponding to open reading frames of ion channel subunit genes including CACNB3 and KCNB1. Moreover, in unstimulated cells, the consensus κB site was identified 2116 times, being defined by 103 different sequence instances of this motif. Of these 2116 consensus κB motifs, 1089 (51.5%) were identified within intronic regions. Parallel expression array analyses in PHM1-31 cultures demonstrated that TNF stimulated a >2-fold induction in 51 genes and a fold repression of >1.5 in 18 others. We identified 14 anti-RelA-serum-enriched genomic regions that correlated with 17 TNF-inducible genes, such as COX2, Egr-1, Jun, IκBα and IL6, as well as five regions associated with TNF-mediated gene repression, including Col1A2

A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions

Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition, and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ∼380 previously unreported PPIs. We validated a subset using surface plasmon resonance and cell binding assays. Observed PPIs reveal a large and complex network of interactions both within and across biological systems. We identified new PPIs for receptors with well-characterized ligands and binding partners for “orphan” receptors. New PPIs include proteins expressed on multiple cell types and involved in diverse processes including immune and nervous system development and function, differentiation/proliferation, metabolism, vascularization, and reproduction. These PPIs provide a resource for further biological investigation into their functional relevance and may offer new therapeutic drug targets

Plutonium Migration during the Leaching of Cemented Radioactive Waste Sludges

One of the most challenging components of the UK nuclear legacy is Magnox sludge, arising from the corrosion of Mg alloy-clad irradiated metallic U fuel that has been stored in high pH ponds. The sludges mainly comprise Mg hydroxide and carbonate phases, contaminated with fission products and actinides, including Pu. Cementation and deep geological disposal is one option for the long-term management of this material, but there is a need to understand how Pu may be leached from the waste, if it is exposed to groundwater. Here, we show that cemented Mg(OH)2 powder prepared with Pu(IV)aq is altered on contact with water to produce a visibly altered ‘leached zone’, which penetrates several hundred microns into the sample. In turn, this zone shows slow leaching of Pu, with long-term leaching rates between 1.8–4.4 × 10−5% of total Pu per day. Synchrotron micro-focus X-ray fluorescence mapping identified decreased Pu concentration within the ‘leached zone’. A comparison of micro-focus X-ray absorption spectroscopy (µ-XAS) spectra collected across both leached and unleached samples showed little variation, and indicated that Pu was present in a similar oxidation state and coordination environment. Fitting of the XANES spectra between single oxidation state standards and EXAFS modeling showed that Pu was present as a mixture of Pu(IV) and Pu(V). The change in Pu oxidation from the stock solution suggests that partial Pu oxidation occurred during sample ageing. Similarity in the XAS spectra from all samples, with different local chemistries, indicated that the Pu oxidation state was not perturbed by macro-scale variations in cement chemistry, surface oxidation, sample aging, or the leaching treatment. These experiments have demonstrated the potential for leaching of Pu from cementitious waste forms, and its underlying significance requires further investigation

A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions

Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition, and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ∼380 previously unreported PPIs. We validated a subset using surface plasmon resonance and cell binding assays. Observed PPIs reveal a large and complex network of interactions both within and across biological systems. We identified new PPIs for receptors with well-characterized ligands and binding partners for “orphan” receptors. New PPIs include proteins expressed on multiple cell types and involved in diverse processes including immune and nervous system development and function, differentiation/proliferation, metabolism, vascularization, and reproduction. These PPIs provide a resource for further biological investigation into their functional relevance and may offer new therapeutic drug targets

Plutonium Migration during the Leaching of Cemented Radioactive Waste Sludges

One of the most challenging components of the UK nuclear legacy is Magnox sludge, arising from the corrosion of Mg alloy-clad irradiated metallic U fuel that has been stored in high pH ponds. The sludges mainly comprise Mg hydroxide and carbonate phases, contaminated with fission products and actinides, including Pu. Cementation and deep geological disposal is one option for the long-term management of this material, but there is a need to understand how Pu may be leached from the waste, if it is exposed to groundwater. Here, we show that cemented Mg(OH)2 powder prepared with Pu(IV)aq is altered on contact with water to produce a visibly altered ‘leached zone’, which penetrates several hundred microns into the sample. In turn, this zone shows slow leaching of Pu, with long-term leaching rates between 1.8–4.4 × 10−5% of total Pu per day. Synchrotron micro-focus X-ray fluorescence mapping identified decreased Pu concentration within the ‘leached zone’. A comparison of micro-focus X-ray absorption spectroscopy (µ-XAS) spectra collected across both leached and unleached samples showed little variation, and indicated that Pu was present in a similar oxidation state and coordination environment. Fitting of the XANES spectra between single oxidation state standards and EXAFS modeling showed that Pu was present as a mixture of Pu(IV) and Pu(V). The change in Pu oxidation from the stock solution suggests that partial Pu oxidation occurred during sample ageing. Similarity in the XAS spectra from all samples, with different local chemistries, indicated that the Pu oxidation state was not perturbed by macro-scale variations in cement chemistry, surface oxidation, sample aging, or the leaching treatment. These experiments have demonstrated the potential for leaching of Pu from cementitious waste forms, and its underlying significance requires further investigation