8,975 research outputs found

    Diversity in parasitic nematode genomes: the microRNAs of Brugia pahangi and Haemonchus contortus are largely novel

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    <b>BACKGROUND:</b> MicroRNAs (miRNAs) play key roles in regulating post-transcriptional gene expression and are essential for development in the free-living nematode Caenorhabditis elegans and in higher organisms. Whether microRNAs are involved in regulating developmental programs of parasitic nematodes is currently unknown. Here we describe the the miRNA repertoire of two important parasitic nematodes as an essential first step in addressing this question. <b>RESULTS:</b> The small RNAs from larval and adult stages of two parasitic species, Brugia pahangi and Haemonchus contortus, were identified using deep-sequencing and bioinformatic approaches. Comparative analysis to known miRNA sequences reveals that the majority of these miRNAs are novel. Some novel miRNAs are abundantly expressed and display developmental regulation, suggesting important functional roles. Despite the lack of conservation in the miRNA repertoire, genomic positioning of certain miRNAs within or close to specific coding genes is remarkably conserved across diverse species, indicating selection for these associations. Endogenous small-interfering RNAs and Piwi-interacting (pi)RNAs, which regulate gene and transposon expression, were also identified. piRNAs are expressed in adult stage H. contortus, supporting a conserved role in germline maintenance in some parasitic nematodes. <b>CONCLUSIONS:</b> This in-depth comparative analysis of nematode miRNAs reveals the high level of divergence across species and identifies novel sequences potentially involved in development. Expression of novel miRNAs may reflect adaptations to different environments and lifestyles. Our findings provide a detailed foundation for further study of the evolution and function of miRNAs within nematodes and for identifying potential targets for intervention

    Radio Astronomical Polarimetry and the Lorentz Group

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    In radio astronomy the polarimetric properties of radiation are often modified during propagation and reception. Effects such as Faraday rotation, receiver cross-talk, and differential amplification act to change the state of polarized radiation. A general description of such transformations is useful for the investigation of these effects and for the interpretation and calibration of polarimetric observations. Such a description is provided by the Lorentz group, which is intimately related to the transformation properties of polarized radiation. In this paper the transformations that commonly arise in radio astronomy are analyzed in the context of this group. This analysis is then used to construct a model for the propagation and reception of radio waves. The implications of this model for radio astronomical polarimetry are discussed.Comment: 10 pages, accepted for publication in Astrophysical Journa

    Increased complexity of Tmem16a/Anoctamin 1 transcript alternative splicing

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    <p>Abstract</p> <p>Background</p> <p>TMEM16A (Anoctamin 1; ANO1) is an eight transmembrane protein that functions as a calcium-activated chloride channel. <it>TMEM16A </it>in human exhibits alternatively spliced exons (6b, 13 and 15), which confer important roles in the regulation of channel function. Mouse <it>Tmem16a </it>is reported to consist of 25 exons that code for a 956 amino acid protein. In this study our aim was to provide details of mouse <it>Tmem16a </it>genomic structure and to investigate if <it>Tmem16a </it>transcript undergoes alternative splicing to generate channel diversity.</p> <p>Results</p> <p>We identified <it>Tmem16a </it>transcript variants consisting of alternative exons 6b, 10, 13, 14, 15 and 18. Our findings indicate that many of these exons are expressed in various combinations and that these splicing events are mostly conserved between mouse and human. In addition, we confirmed the expression of these exon variants in other mouse tissues. Additional splicing events were identified including a novel conserved exon 13b, tandem splice sites of exon 1 and 21 and two intron retention events.</p> <p>Conclusion</p> <p>Our results suggest that <it>Tmem16a </it>gene is significantly more complex than previously described. The complexity is especially evident in the region spanning exons 6 through 16 where a number of the alternative splicing events are thought to affect calcium sensitivity, voltage dependence and the kinetics of activation and deactivation of this calcium-activated chloride channel. The identification of multiple <it>Tmem16a </it>splice variants suggests that alternative splicing is an exquisite mechanism that operates to diversify TMEM16A channel function in both physiological and pathophysiological conditions.</p

    Predicting the contributions of novel marine prey resources from angling and anadromy to the diet of a freshwater apex predator

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    1. Anadromous fishes can be important prey resources for piscivorous fauna in lowland rivers. Freshwater anglers exploiting large-bodied cypriniform fishes use high quantities of pelletized marine fishmeal baits that can contribute substantially to fish diets. This marine-derived energy pathway also potentially provides a marine prey resource for freshwater piscivores. However, large-bodied cypriniform fishes are often in a size refuge against predation due to their large sizes. 2. Stable isotope (δ15N and δ13C) analysis assessed how novel marine prey resources influenced the diet of a freshwater apex predator, Northern pike Esox lucius, in an impounded river basin (lower River Severn, Western England). Up to three groups of prey resources were present: anadromous European shad (Alosa spp.), cypriniform fishes with dietary specialisms based on marine fishmeal baits, and freshwater prey. The availability of these prey resources to E. lucius varied according to river connectivity and levels of angling exploitation in different river reaches. 3. Where the three prey groups were present, E. lucius were more enriched in δ13C values (range: -24.74 to -16.34 ‰) compared to river reaches where aspects of the marine prey groups were absent. (range: -28.30 to -21.47) In all reaches, δ13C increased as E. lucius length increased. In the reach where all prey groups were present, the isotopic niches of three E. lucius size classes were strongly partitioned; this was not apparent in reaches where the marine pathways were unavailable. 4. Stable isotope mixing models suggested that freshwater prey were the most important prey item, contributing between 42 and 96 % to the diet of individual E. lucius. However, where present, anadromous fishes and cypriniform fishes specialising on marine fishmeal baits were also important prey items, contributing substantially to the diet of larger E. lucius (length > 650 mm). The total dietary contributions of the marine resources varied considerably among the individual larger fish (22 to 58 % of total diet). 5. The presence of two marine resource pathways in a lowland river thus strongly influenced the diet of an apex predator, but with contributions being a function of their spatial availability, E. lucius body size and individual trophic specialisations. These results emphasise how the anthropogenic activities of river engineering and human subsidies can affect the trophic dynamics of apex predators

    The effect of worrying on intolerance of uncertainty and positive and negative beliefs about worry

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    Background and Objectives: The effect of a worry manipulation on the clinical constructs intolerance of uncertainty (IU), negative beliefs about the consequences of worry (NCOW), positive beliefs about the consequences of worry (PCOW), in addition to the emotions anxiety and sadness, was examined. Methods: A non-clinical sample was split into two groups, a worry group (n = 29), who were asked to generate 20 potential worries about a hypothetical scenario, and a control group (n = 28), who were asked to generate 2 potential worries about the same scenario. Subsequently, participants were asked to complete measures of IU, NCOW, PCOW, sadness and anxiety. Results: The worry group scored significantly higher than the control group on measures of IU, NCOW and PCOW but not on measures of sadness and anxiety. Limitations: Possible limitations of the current study include the use of a student sample and the use of a hypothetical worry scenario. Conclusions: The results suggest that engaging in worry can increase scores on measures of the beliefs and thought patterns often used to causally explain worry. The results are in line with recent research showing bidirectionality between anxiety related symptoms and their associated clinical constructs, and are consistent with an approach which sees anxiety symptoms as part of an evolved integrated threat management system that alerts the individual to threats to goals or challenges, and coordinates cognitive, behavioral, and affective reactions to enable effective responding to these threats and challenges

    High resolution characterisation of microstructural evolution in Rbx_{x}Fe2−y_{2-y}Se2_{2} crystals on annealing

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    The superconducting and magnetic properties of phase-separated Ax_xFe2−y_{2-y}Se2_2 compounds are known to depend on post-growth heat treatments and cooling profiles. This paper focusses on the evolution of microstructure on annealing, and how this influences the superconducting properties of Rbx_xFe2−y_2-ySe2_2 crystals. We find that the minority phase in the as-grown crystal has increased unit cell anisotropy (c/a ratio), reduced Rb content and increased Fe content compared to the matrix. The microstructure is rather complex, with two-phase mesoscopic plate-shaped features aligned along {113} habit planes. The minority phase are strongly facetted on the {113} planes, which we have shown to be driven by minimising the volume strain energy introduced as a result of the phase transformation. Annealing at 488K results in coarsening of the mesoscopic plate-shaped features and the formation of a third distinct phase. The subtle differences in structure and chemistry of the minority phase(s) in the crystals are thought to be responsible for changes in the superconducting transition temperature. In addition, scanning photoemission microscopy has clearly shown that the electronic structure of the minority phase has a higher occupied density of states of the low binding energy Fe3d orbitals, characteristic of crystals that exhibit superconductivity. This demonstrates a clear correlation between the Fe-vacancy-free phase with high c/a ratio and the electronic structure characteristics of the superconducting phase.Comment: 6 figures v2 is exactly the same as v1. The typesetting errors in the abstract have been correcte

    Protein kinase C theta is required for efficient induction of IL-10-secreting T cells

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    <div><p>Secretion of interleukin-10 (IL-10) by CD4<sup>+</sup> T cells is an essential immunoregulatory mechanism. The work presented here assesses the role of the signaling molecule protein kinase C theta (PKCθ) in the induction of IL-10 expression in CD4<sup>+</sup> T cells. Using wildtype and PKCθ-deficient Tg4 T cell receptor transgenic mice, we implemented a well-described protocol of repeated doses of myelin basic protein (MBP)Ac1-9[4Y] antigen to induce Tr1-like IL-10<sup>+</sup> T cells. We find that PKCθ is required for the efficient induction of IL-10 following antigen administration. Both serum concentrations of IL-10 and the proportion of IL-10<sup>+</sup> T cells were reduced in PKCθ-deficient mice relative to wildtype mice following [4Y] treatment. We further characterized the T cells of [4Y] treated PKCθ-deficient Tg4 mice and found reduced expression of the transcription factors cMaf, Nfil3 and FoxP3 and the surface receptors PD-1 and Tim3, all of which have been associated with the differentiation or function of IL-10<sup>+</sup> T cells. Finally, we demonstrated that, unlike [4Y] treated wildtype Tg4 T cells, cells from PKCθ-deficient mice were unable to suppress the priming of naïve T cells <i>in vitro</i> and <i>in vivo</i>. In summary, we present data demonstrating a role for PKCθ in the induction of suppressive, IL-10-secreting T cells induced in TCR-transgenic mice following chronic antigen administration. This should be considered when contemplating PKCθ as a suitable drug target for inducing immune suppression and graft tolerance.</p></div
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