The [α/Fe]-[Fe/H] relation in the E-MOSAICS simulations: its connection to the birth place of globular clusters and the fraction of globular cluster field stars in the bulge

The {\alpha}-element abundances of the globular cluster (GC) and field star populations of galaxies encode information about the formation of each of these components. We use the E-MOSAICS cosmological simulations of ~L* galaxies and their GCs to investigate the [{\alpha}/Fe]-[Fe/H] distribution of field stars and GCs in 25 Milky Way-mass galaxies. The [{\alpha}/Fe]-[Fe/H] distribution go GCs largely follows that of the field stars and can also therefore be used as tracers of the [{\alpha}/Fe]-[Fe/H] evolution of the galaxy. Due to the difference in their star formation histories, GCs associated with stellar streams (i.e. which have recently been accreted) have systematically lower [{\alpha}/Fe] at fixed [Fe/H]. Therefore, if a GC is observed to have low [{\alpha}/Fe] for its [Fe/H] there is an increased probability that this GC was accreted recently alongside a dwarf galaxy. There is a wide range of shapes for the field star [{\alpha}/Fe]-[Fe/H] distribution, with a notable subset of galaxies exhibiting bimodal distributions, in which the high [{\alpha}/Fe] sequence is mostly comprised of stars in the bulge, a high fraction of which are from disrupted GCs. We calculate the contribution of disrupted GCs to the bulge component of the 25 simulated galaxies and find values between 0.3-14 per cent, where this fraction correlates with the galaxy's formation time. The upper range of these fractions is compatible with observationally-inferred measurements for the Milky Way, suggesting that in this respect the Milky Way is not typical of L* galaxies, having experienced a phase of unusually rapid growth at early times

Wolbachia in the flesh: symbiont intensities in germ-line and somatic tissues challenge the conventional view of Wolbachia transmission routes

Symbionts can substantially affect the evolution and ecology of their hosts. The investigation of the tissue-specific distribution of symbionts (tissue tropism) can provide important insight into host-symbiont interactions. Among other things, it can help to discern the importance of specific transmission routes and potential phenotypic effects. The intracellular bacterial symbiont Wolbachia has been described as the greatest ever panzootic, due to the wide array of arthropods that it infects. Being primarily vertically transmitted, it is expected that the transmission of Wolbachia would be enhanced by focusing infection in the reproductive tissues. In social insect hosts, this tropism would logically extend to reproductive rather than sterile castes, since the latter constitute a dead-end for vertically transmission. Here, we show that Wolbachia are not focused on reproductive tissues of eusocial insects, and that non-reproductive tissues of queens and workers of the ant Acromyrmex echinatior, harbour substantial infections. In particular, the comparatively high intensities of Wolbachia in the haemolymph, fat body, and faeces, suggest potential for horizontal transmission via parasitoids and the faecal-oral route, or a role for Wolbachia modulating the immune response of this host. It may be that somatic tissues and castes are not the evolutionary dead-end for Wolbachia that is commonly thought

The cost of promiscuity: sexual transmission of Nosema microsporidian parasites in polyandrous honey bees

Multiple mating (and insemination) by females with different males, polyandry, is widespread across animals, due to material and/or genetic benefits for females. It reaches particularly high levels in some social insects, in which queens can produce significantly fitter colonies by being polyandrous. It is therefore a paradox that two thirds of eusocial hymenopteran insects appear to be exclusively monandrous, in spite of the fitness benefits that polyandry could provide. One possible cost of polyandry could be sexually transmitted parasites, but evidence for these in social insects is extremely limited. Here we show that two different species of Nosema microsporidian parasites can transmit sexually in the honey bee Apis mellifera. Honey bee males that are infected by the parasite have Nosema spores in their semen, and queens artificially inseminated with either Nosema spores or the semen of Nosema-infected males became infected by the parasite. The emergent and more virulent N. ceranae achieved much higher rates of infection following insemination than did N. apis. The results provide the first quantitative evidence of a sexually transmitted disease (STD) in social insects, indicating that STDs may represent a potential cost of polyandry in social insects

Improving the management of pain from advanced cancer in the community: study protocol for a pragmatic multi-centre randomised controlled trial

Introduction: For patients with advanced cancer, research shows that pain is frequent, burdensome and undertreated. Evidence-based approaches to support cancer pain management have been developed but have not been implemented within the context of the UK National Health Service. This protocol is for a pragmatic multi-centre randomised controlled trial to assess feasibility, acceptability, effectiveness and cost effectiveness for a multi-component intervention for pain management in patients with advanced cancer. Methods and Analysis: This trial will assess the feasibility of implementation and uptake of evidence based interventions, developed and piloted as part of the IMPACCT Programme grant, into routine clinical practice and determine whether there are potential differences with respect to patient rated pain, patient pain knowledge and experience, healthcare use, quality of life, and cost effectiveness. 160 patients will receive either the intervention (usual care plus supported self-management) delivered within the oncology clinic and palliative care services by locally assigned community palliative care nurses, consisting of a self-management educational intervention and eHealth intervention for routine pain assessment and monitoring; or usual care. The primary outcomes are to assess implementation and uptake of the interventions, and differences in terms of pain severity. Secondary outcomes include pain interference, participant pain knowledge and experience, and cost effectiveness. Outcome assessment will be blinded and patient reported outcome measures collected via post at 6 and 12 weeks following randomisation. Ethics and Dissemination: This RCT has the potential to significantly influence NHS service delivery to community based patients with pain from advanced cancer. We aim to provide definitive evidence of whether two simple interventions delivered by community palliative care nurse in palliative care that support-self-management are clinically and cost effective additions to standard community palliative care

RepSeq-A database of amino acid repeats present in lower eukaryotic pathogens

BACKGROUND Amino acid repeat-containing proteins have a broad range of functions and their identification is of relevance to many experimental biologists. In human-infective protozoan parasites (such as the Kinetoplastid and Plasmodium species), they are implicated in immune evasion and have been shown to influence virulence and pathogenicity. RepSeq http://repseq.gugbe.com is a new database of amino acid repeat-containing proteins found in lower eukaryotic pathogens. The RepSeq database is accessed via a web-based application which also provides links to related online tools and databases for further analyses. RESULTS The RepSeq algorithm typically identifies more than 98% of repeat-containing proteins and is capable of identifying both perfect and mismatch repeats. The proportion of proteins that contain repeat elements varies greatly between different families and even species (3 - 35% of the total protein content). The most common motif type is the Sequence Repeat Region (SRR) - a repeated motif containing multiple different amino acid types. Proteins containing Single Amino Acid Repeats (SAARs) and Di-Peptide Repeats (DPRs) typically account for 0.5 - 1.0% of the total protein number. Notable exceptions are P. falciparum and D. discoideum, in which 33.67% and 34.28% respectively of the predicted proteomes consist of repeat-containing proteins. These numbers are due to large insertions of low complexity single and multi-codon repeat regions. CONCLUSION The RepSeq database provides a repository for repeat-containing proteins found in parasitic protozoa. The database allows for both individual and cross-species proteome analyses and also allows users to upload sequences of interest for analysis by the RepSeq algorithm. Identification of repeat-containing proteins provides researchers with a defined subset of proteins which can be analysed by expression profiling and functional characterisation, thereby facilitating study of pathogenicity and virulence factors in the parasitic protozoa. While primarily designed for kinetoplastid work, the RepSeq algorithm and database retain full functionality when used to analyse other species

Canrightiopsis, a new Early Cretaceous fossil with Clavatipollenites-type pollen bridge the gap between extinct Canrightia and extant Chloranthaceae

Canrightiopsis with three species (C. intermedia, C. crassitesta, C. dinisii) is described from the Early Cretaceous of Portugal based on small, one-seeded berries. The fruits are derived from bisexual flowers with three stamens borne on one side of the ovary. There are no traces of a perianth. Pollen is of the Clavatipollenites-type, monocolpate, semitectate, reticulate-columellate with heterobrochate reticulum and muri with beaded supratectal ornamentation. The ovary is unilocular with a single pendant, orthotropous and bitegmic ovule. The seed is endotestal. The endotesta consists of one layer of palisade-shaped crystal cells with fibrous infillings. The fruit wall has resin bodies or cavities from presumed ethereal oil cells sometimes seen as stomata-like structures on the fruit surface. A phylogenetic analysis resolves Canrightiopsis as a close relative of extant Chloranthaceae, particularly close to extant Chloranthus and Sarcandra. All three taxa share the one-sided position of the stamens on the ovary. An evolutionary sequence from fossil Canrightia to fossil Canrightiopsis and extant Chloranthus and Sarcandra is suggested by loss of perianth, reduction in number of ovules and stamens and displacement of stamens to one side of the ovary. Canrightiopsis also shares several critical features with extant Ascarina including monoaperturate pollen and beaded supratectal ornamentation of the pollen wall.Swiss Light Source (European Union) [20110963, 20130185]; Swedish Research Council [621-2011-5431]; CretaCarbo project [PTDC/CTE-GIX/113983/2009]info:eu-repo/semantics/publishedVersio

Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells

Low fruit and vegetable consumption and high saturated fat consumption causes elevated circulating cholesterol and are breast cancer risk factors. During cholesterol metabolism, oxysterols form that bind and activate the liver X receptors (LXRs). Oxysterols halt breast cancer cell proliferation but enhance metastatic colonization, indicating tumour suppressing and promoting roles. Phytosterols and phytostanols in plants, like cholesterol in mammals, are essential components of the plasma membrane and biochemical precursors, and in human cells can alter LXR transcriptional activity. Here, a panel of breast cancer cell lines were treated with four dietary plant sterols and a stanol, alone or in combination with oxysterols. LXR activation and repression were measured by gene expression and LXR-luciferase reporter assays. Oxysterols activated LXR in all cell lines, but surprisingly phytosterols failed to modulate LXR activity. However, phytosterols significantly inhibited the ability of oxysterols to drive LXR transcription. These data support a role for phytosterols in modulating cancer cell behaviour via LXR, and therefore suggest merit in accurate dietary recordings of these molecules in cancer patients during treatment and perhaps supplementation to benefit recovery

Characterization and prognostic value of LXR splice variants in triple-negative breast cancer

Activity of liver x receptor (LXR), the homeostatic regulator of cholesterol metabolism, is elevated in triple-negative breast cancer (BCa) relative to other BCa subtypes, driving drug resistance and metastatic gene signatures. The loci encoding LXRα and LXRβ produce multiple alternatively spliced proteins, but the true range of variants and their relevance to cancer remain poorly defined. Here, we report seven LXR splice variants, three of which have not previously been reported and five that were prognostic for disease-free survival. Expression of full-length LXRα splice variants was associated with poor prognosis, consistent with a role as an oncogenic driver of triple-negative tumor pathophysiology. Contrary to this was the observation that high expression of truncated LXRα splice variants or any LXRβ splice variant was associated with longer survival. These findings indicate that LXR isoform abundance is an important aspect of understanding the link between dysregulated cholesterol metabolism and cancer pathophysiology

Vigorous star formation hidden by dust in a galaxy at z=1.4z=1.4

Near-infrared surveys have revealed a substantial population of enigmatic faint galaxies with extremely red optical-to-near-infrared colours and with a sky surface density comparable to that of faint quasars. There are two scenarios for these extreme colours: (i) these distant galaxies have formed virtually all their stars at very high redshifts and, due to the absence of recently formed stars, the colours are extremely red and (ii) these distant galaxies contain large amounts of dust, severely reddening the rest-frame UV--optical spectrum. HR10 ($z = 1.44$) is considered the archetype of the extremely red galaxies. Here we report the detection of the continuum emission from HR10 at 850$\mu$m and at 1250$\mu$m, demonstrating that HR10 is a very dusty galaxy undergoing a major episode of star formation. Our result provides a clear example of a high-redshift galaxy where the star formation rate inferred from the ultraviolet luminosity would be underestimated by a factor up to 1000, and shows that great caution should be used to infer the global star formation history of the Universe from optical observations only.Comment: 12 pages, 1 figure, Nature, in press (30 April 1998