An integrated approach to assess the impacts of zinc pyrithione at different levels of biological organization in marine mussels.

The mechanisms of sublethal toxicity of the antifouling biocide, zinc pyrithione (ZnPT), have not been well-studied. This investigation demonstrates that 14-d sublethal exposure to ZnPT (0.2 or 2 μM, alongside inorganic Zn and sea water controls) is genotoxic to mussel haemocytes but suggests that this is not caused by oxidative DNA damage as no significant induction of oxidised purines was detected by Fpg-modified comet assay. More ecologically relevant endpoints, including decreased clearance rate (CR), cessation of attachment and decreased tolerance of stress on stress (SoS), also showed significant response to ZnPT exposure. Our integrated approach was underpinned by molecular analyses (qRT-PCR of stress-related genes, 2D gel electrophoresis of proteins) that indicated ZnPT causes a decrease in phosphoenolpyruvate carboxykinase (PEPCK) expression in mussel digestive glands, and that metallothionein genes are upregulated; PEPCK downregulation suggests that altered energy metabolism may also be related to the effects of ZnPT. Significant relationships were found between % tail DNA (comet assay) and all higher level responses (CR, attachment, SoS) in addition to PEPCK expression. Principal component analyses suggested that expression of selected genes described more variability within groups whereas % tail DNA reflected different ZnPT concentrations

Exposure to tritiated water at an elevated temperature: Genotoxic and transcriptomic effects in marine mussels (M. galloprovincialis).

Temperature is an abiotic factor of particular concern for assessing the potential impacts of radionuclides on marine species. This is particularly true for tritium, which is discharged as tritiated water (HTO) in the process of cooling nuclear institutions. Additionally, with sea surface temperatures forecast to rise 0.5 - 3.5 C in the next 30-100 years, determining the interaction of elevated temperature with radiological exposure has never been more relevant. We assessed the tissue-specific accumulation, transcriptional expression of key genes, and genotoxicity of tritiated water to marine mussels at either 15 or 25 C, over a 7 day time course with sampling after 1 h, 12 h, 3 d and 7d. The activity concentration used (15 MBq L-1) resulted in tritium accumulation that varied with both time and temperature, but consistently produced dose rates (calculated using the ERICA tool) of <20 Gy h-1, i.e. considerably below the recommended guidelines of the IAEA and EURATOM. Despite this, there was significant induction of DNA strand breaks (as measured by the comet assay), which also showed a temperature-dependent time shift. At 15 C, DNA damage was only significantly elevated after 7 d, in contrast to 25 C where a similar response was observed after only 3 d. The transcription profiles of two isoforms of hsp70, hsp90, mt20, p53 and rad51 indicated potential mechanisms behind this temperature-induced acceleration of genotoxicity, which may be the result of compromised defence. Specifically, genes involved in protein folding, DNA double strand break repair and cell cycle checkpoint control were upregulated after 3 d HTO exposure at 15 C, but significantly downregulated when the same exposure occurred at 25 C. This study is the first to investigate temperature efects on radiation-induced genotoxicity in an ecologically relevant marine invertebrate, Mytilus galloprovincialis. From an ecological perspective, our study suggests that mussels (or similar marine species) exposed to increased temperature and HTO may have a compromised ability to defend against genotoxic stress. Abbreviations: HTO, tritiated water; Fpg, formamidopyrimidine glyco- sylase; GoI, gene of interest; LSC, liquid scintillation counting; tDAC, tissue dry activity concentration; TFWT, tissue free water tritium; tTAC, tissue total activity concentration; woTAC, whole organism total activity concentration

Limited hybridization between introduced and Critically Endangered indigenous tilapia fishes in northern Tanzania

Hybridization between introduced and indigenous species can lead to loss of unique genetic resources and precipitate extinction. In Tanzania, the Nile tilapia (Oreochromis niloticus) and blue-spotted tilapia (Oreochromis leucostictus) have been widely introduced to non-native habitats for aquaculture and development of capture fisheries. Here, we aimed to quantify interspecific hybridization between these introduced species and the indigenous species Oreochromis esculentus, Oreochromis jipe and Oreochromis korogwe. In the Pangani basin, several hybrids were observed (O. niloticus × O. jipe, O. leucostictus × O. jipe, O. niloticus × O. korogwe), although hybrids were relatively uncommon within samples relative to purebreds. Hybrids between the native O. jipe × O. korogwe were also observed. In the Lake Victoria basin, no evidence of hybrids was found. Analysis of body shape using geometric morphometrics suggested that although purebreds could be discriminated from one another, hybrids could not be readily identified on body and head shape alone. These results provide the first evidence of hybridization between the introduced species and the Critically Endangered O. jipe in Tanzania. Given uncertainty regarding benefits of introduced species over large-bodied indigenous species in aquaculture and capture fisheries, we suggest that future introductions of hybridization-prone species should be carefully evaluated

Treating multiple sclerosis with generic cladribine

Meeting AbstractEuropean Comm Treatment & Res Multiple Sclerosi

Molecular phylogeny of Oreochromis (Cichlidae: Oreochromini) reveals mito-nuclear discordance and multiple colonisation of adverse aquatic environments

Although the majority of cichlid diversity occurs in the African Great Lakes, these fish have also diversified across the African continent. Such continental radiations, occurring in both rivers and lakes have received far less attention than lacustrine radiations despite some members, such as the oreochromine cichlids (commonly referred to as ‘tilapia’), having significant scientific and socioeconomic importance both within and beyond their native range. Unique among cichlids, several species of the genus Oreochromis exhibit adaptation to soda conditions (including tolerance of elevated temperatures and salinity), which are of interest from evolutionary biology research and aquaculture perspectives. Questions remain regarding the factors facilitating the diversification of this group, which to date have not been addressed within a phylogenetic framework. Here we present the first comprehensive (32/37 described species) multi-marker molecular phylogeny of Oreochromis and closely related Alcolapia, based on mitochondrial (1583 bp) and nuclear (3092 bp) sequence data. We show widespread discordance between nuclear DNA and mitochondrial DNA trees. This could be the result of incomplete lineage sorting and/or introgression in mitochondrial loci, although we didn’t find a strong signal for the latter. Based on our nuclear phylogeny we demonstrate that adaptation to adverse conditions (elevated salinity, temperature, or alkalinity) has occurred multiple times within Oreochromis, but that adaptation to extreme (soda) conditions (high salinity, temperature, and alkalinity) has likely arisen once in the lineage leading to O. amphimelas and Alcolapia. We also show Alcolapia is nested within Oreochromis, which is in agreement with previous studies, and here revise the taxonomy to synonymise the genus in Oreochromis, retaining the designation as subgenus Oreochromis (Alcolapia)

An 800-million-solar-mass black hole in a significantly neutral Universe at redshift 7.5

Quasars are the most luminous non-transient objects known and as a result they enable studies of the Universe at the earliest cosmic epochs. Despite extensive efforts, however, the quasar ULAS J1120+0641 at z=7.09 has remained the only one known at z>7 for more than half a decade. Here we report observations of the quasar ULAS J134208.10+092838.61 (hereafter J1342+0928) at redshift z=7.54. This quasar has a bolometric luminosity of 4e13 times the luminosity of the Sun and a black hole mass of 8e8 solar masses. The existence of this supermassive black hole when the Universe was only 690 million years old---just five percent of its current age---reinforces models of early black-hole growth that allow black holes with initial masses of more than about 1e4 solar masses or episodic hyper-Eddington accretion. We see strong evidence of absorption of the spectrum of the quasar redwards of the Lyman alpha emission line (the Gunn-Peterson damping wing), as would be expected if a significant amount (more than 10 per cent) of the hydrogen in the intergalactic medium surrounding J1342+0928 is neutral. We derive a significant fraction of neutral hydrogen, although the exact fraction depends on the modelling. However, even in our most conservative analysis we find a fraction of more than 0.33 (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing well within the reionization epoch of the Universe.Comment: Updated to match the final journal versio

The Thermal Design, Characterization, and Performance of the SPIDER Long-Duration Balloon Cryostat

We describe the SPIDER flight cryostat, which is designed to cool six millimeter-wavelength telescopes during an Antarctic long-duration balloon flight. The cryostat, one of the largest to have flown on a stratospheric payload, uses liquid helium-4 to deliver cooling power to stages at 4.2 and 1.6 K. Stainless steel capillaries facilitate a high flow impedance connection between the main liquid helium tank and a smaller superfluid tank, allowing the latter to operate at 1.6 K as long as there is liquid in the 4.2 K main tank. Each telescope houses a closed cycle helium-3 adsorption refrigerator that further cools the focal planes down to 300 mK. Liquid helium vapor from the main tank is routed through heat exchangers that cool radiation shields, providing negative thermal feedback. The system performed successfully during a 17 day flight in the 2014-2015 Antarctic summer. The cryostat had a total hold time of 16.8 days, with 15.9 days occurring during flight.Comment: 15 pgs, 17 fig

Models of Star-Planet Magnetic Interaction

Magnetic interactions between a planet and its environment are known to lead to phenomena such as aurorae and shocks in the solar system. The large number of close-in exoplanets that were discovered triggered a renewed interest in magnetic interactions in star-planet systems. Multiple other magnetic effects were then unveiled, such as planet inflation or heating, planet migration, planetary material escape, and even modification of the host star properties. We review here the recent efforts in modelling and understanding magnetic interactions between stars and planets in the context of compact systems. We first provide simple estimates of the effects of magnetic interactions and then detail analytical and numerical models for different representative scenarii. We finally lay out a series of future developments that are needed today to better understand and constrain these fascinating interactions.Comment: 23 pages, 10 figures, accepted as a chapter in the Handbook of Exoplanet

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response