Candida albicans Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation

Received 28 August 2014 Accepted 28 October 2014 Published 2 December 2014 This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license. ACKNOWLEDGMENTS We thank Janet Willment, Aberdeen Fungal Group, University of Aberdeen, for kindly providing the soluble Dectin-1-Fc reporter. All microscopy was performed with the assistance of the University of Aberdeen Core Microscopy & Histology Facility, and we thank the IFCC for their assistance with flow cytometry. We thank the Wellcome Trust for funding (080088, 086827, 075470, 099215, 097377, and 101873). E.R.B. and A.J.P.B. are funded by the European Research Council (ERC-2009-AdG-249793), and J.L. is funded by a Medical Research Council Clinical Training Fellowship.Peer reviewedPublisher PD

miR-515-5p controls cancer cell migration through MARK4 regulation

Here, we show that miR-515-5p inhibits cancer cell migration and metastasis. RNA-seq analyses of both oestrogen receptor receptor-positive and receptor-negative breast cancer cells overexpressing miR-515-5p reveal down-regulation of NRAS, FZD4, CDC42BPA, PIK3C2B and MARK4 mRNAs. We demonstrate that miR-515-5p inhibits MARK4 directly 3' UTR interaction and that MARK4 knock-down mimics the effect of miR-515-5p on breast and lung cancer cell migration. MARK4 overexpression rescues the inhibitory effects of miR-515-5p, suggesting miR-515-5p mediates this process through MARK4 down-regulation. Furthermore, miR-515-5p expression is reduced in metastases compared to primary tumours derived from both in vivo xenografts and samples from patients with breast cancer. Conversely, miR-515-5p overexpression prevents tumour cell dissemination in a mouse metastatic model. Moreover, high miR-515-5p and low MARK4 expression correlate with increased breast and lung cancer patients' survival, respectively. Taken together, these data demonstrate the importance of miR-515-5p/MARK4 regulation in cell migration and metastasis across two common cancers

Improved phylogenetic resolution within Siphonophora (Cnidaria) with implications for trait evolution

Siphonophores are a diverse group of hydrozoans (Cnidaria) that are found at most depths of the ocean - from the surface, like the familiar Portuguese man of war, to the deep sea. They play important roles in ocean ecosystems, and are among the most abundant gelatinous predators. A previous phylogenetic study based on two ribosomal RNA genes provided insight into the internal relationships between major siphonophore groups. There was, however, little support for many deep relationships within the clade Codonophora. Here, we present a new siphonophore phylogeny based on new transcriptome data from 29 siphonophore species analyzed in combination with 14 publicly available genomic and transcriptomic datasets. We use this new phylogeny to reconstruct several traits that are central to siphonophore biology, including sexual system (monoecy vs. dioecy), gain and loss of zooid types, life history traits, and habitat. The phylogenetic relationships in this study are largely consistent with the previous phylogeny, but we find strong support for new clades within Codonophora that were previously unresolved. These results have important implications for trait evolution within Siphonophora, including favoring the hypothesis that monoecy arose at least twice

Temperature effects on larval development in the lithodid crab Lithodes maja

Physiological adaptations enabling tolerance of low temperature, as well as adaptations in larval development, are thought to be critical to the global radiation of deep-water lineages of lithodine crabs. However, global climate change is warming the oceans, potentially impacting the biogeographic distributions of these large predatory crabs. To date, larval thermal scope has only been explored in a few deep-water lineage lithodines. We assessed larval development parameters in the northern stone crab Lithodes maja at temperatures ranging from 1 °C to 15 °C. We examined larval survival, duration of development, energetic reserve utilisation, and respiration rate. L. maja larvae displayed a narrow thermal tolerance window and metamorphosed successfully at 6 °C only. Differential uses of energetic reserves among temperatures during development in L. maja support the interpretation of a narrow larval thermal scope and indicate that 6 °C is the optimum temperature for development in this species. Consequently, continued ocean warming is likely to force biogeographic range shifts in L. maja.</p

Temperature adaptation in larval development of lithodine crabs from deep-water lineages

Adaptations in per-offspring investment and larval development are considered to have been crucial to the global radiation of deep-water lineages of lithodine crabs (Lithodinae). Temperature is proposed to drive latitudinal trends in energy provisioning of eggs in marine invertebrates, mediated by thermally dependent intraspecific plasticity in per-offspring investment. Consequently, a changing climate may be expected to directly affect larval provisioning. We analysed available data to examine any differences in per-offspring investment and larval development among deep-water lineage lithodines. Although data are few, interspecific differences in the thermal scope of deep-water-lineage lithodine larvae appear coupled with differences in biogeography. This coupling suggests environmental temperature influences larval thermal scope. Lithodine phylogeography suggests that larval cold-eurythermy in deep-water-lineage lithodines is a derived trait that has evolved in relatively warm and variable subantarctic shallow water. Therefore, we hypothesise that capacity to adapt to warmer and more variable environmental conditions may afford deep-water-lineage lithodines some resilience to ocean warming, depending on the rates of environmental and adaptive change. Interspecific comparisons also suggest that larval duration and per-offspring investment are positively correlated. Faster development at a given temperature is associated with higher respiration rates and greater energetic reserve utilisation. Therefore, we hypothesise that selection pressure for contrasting metabolic adaptations in different thermal environments contributes to shifts in larval duration and per-offspring investment

Developing Vulnerability: A Situational Response to the Abuse of Women with Mental Disabilities

In this paper I present a critical analysis of the English law relating to the safeguarding of vulnerable adults, in particular how the law impacts on the sexual lives of adult women with mental disabilities. I consider the discourses of vulnerability that surround the different legal regimes and whether the emerging theoretical vulnerability literature can assist in developing more nuanced legal responses. I argue that the inherent jurisdiction and Care Act 2014 provide an opportunity to move away from the focus on inherent features of vulnerability such as mental disability towards a more nuanced, situational and embodied account of what it means to safeguard ‘vulnerable adults’. This has the potential to be developed in England through the new legal framework of the Care Act and can be achieved through targeting interventions against the situational causes of vulnerability, for example the perpetrators of sexual violence

Cashless Welfare Transfers for ‘Vulnerable’ Welfare Recipients: Law, Ethics and Vulnerability

This article aims to contribute to literature on the conceptualisation of ‘vulnerability’ and its use by neo-liberal welfare regimes to demean, stigmatize and responsibilize welfare recipients. Several conceptions of ‘vulnerability’ will be explored and utilised in the context of welfare reforms that purport to regulate social security recipients as highly risky ‘vulnerable’ subjects. However, as this article will make clear, ‘vulnerability’ is a somewhat slippery concept and one susceptible to abuse by powerful interests intent on increasing coercive surveillance, discipline and disentitlement for those designated as ‘vulnerable’. Legislation enacted ostensibly to address the ‘vulnerability’ of welfare recipients can foster intensive regulation and it must be asked who benefits most from such arrangements and the rhetoric that supports them.Full Tex