243 research outputs found

    The evolution of reproductive isolation in a simultaneous hermaphrodite, the freshwater snail Physa

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    <p>Abstract</p> <p>Background</p> <p>The cosmopolitan freshwater snail <it>Physa acuta </it>has recently found widespread use as a model organism for the study of mating systems and reproductive allocation. Mitochondrial DNA phylogenies suggest that <it>Physa carolinae</it>, recently described from the American southeast, is a sister species of <it>P. acuta</it>. The divergence of the <it>acuta/carolinae </it>ancestor from the more widespread <it>P. pomilia </it>appears to be somewhat older, and the split between a hypothetical <it>acuta/carolinae/pomilia </it>ancestor and <it>P. gyrina </it>appears older still.</p> <p>Results</p> <p>Here we report the results of no-choice mating experiments yielding no evidence of hybridization between <it>gyrina </it>and any of four other populations (<it>pomilia, carolinae</it>, Philadelphia <it>acuta</it>, or Charleston <it>acuta</it>), nor between <it>pomilia </it>and <it>carolinae</it>. Crosses between <it>pomilia </it>and both <it>acuta </it>populations yielded sterile F1 progeny with reduced viability, while crosses between <it>carolinae </it>and both <it>acuta </it>populations yielded sterile F1 hybrids of normal viability. A set of mate-choice tests also revealed significant sexual isolation between <it>gyrina </it>and all four of our other <it>Physa </it>populations, between <it>pomilia </it>and <it>carolinae</it>, and between <it>pomilia </it>and Charleston <it>acuta</it>, but not between <it>pomilia </it>and the <it>acuta </it>population from Philadelphia, nor between <it>carolinae </it>and either <it>acuta </it>population. These observations are consistent with the origin of hybrid sterility prior to hybrid inviability, and a hypothesis that speciation between <it>pomilia </it>and <it>acuta </it>may have been reinforced by selection for prezygotic reproductive isolation in sympatry.</p> <p>Conclusions</p> <p>We propose a two-factor model for the evolution of postzygotic reproductive incompatibility in this set of five <it>Physa </it>populations consistent with the Dobzhansky-Muller model of speciation, and a second two-factor model for the evolution of sexual incompatibility. Under these models, species trees may be said to correspond with gene trees in American populations of the freshwater snail, <it>Physa</it>.</p

    Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3

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    TLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1. Only the late pathway requires kinase competent RIPK3 and MLKL function. Mechanistically, FADD/caspase-8 scaffolding function provides a post-translational signal 1 in the intermediate pathway, whereas in the late pathway it helps the oligomerization of RIPK3, which together with MLKL provides both signal 1 and 2 for inflammasome assembly. Cytoplasmic dsRNA activates NLRP3 independent of TRIF, RIPK1, RIPK3 or mitochondrial DRP1, but requires FADD/caspase-8 in wildtype macrophages to remove RIPK3 inhibition. Our study provides a comprehensive analysis of pathways that lead to NLRP3 inflammasome activation in response to dsRNA

    What’s on trial? The making of field experiments in international development

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    In the last 20 years, the drive for evidence‐based policymaking has been coupled with a concurrent push for the use of randomized controlled trials (RCTs) as the “gold‐standard” for generating rigorous evidence on whether or not development interventions work. Drawing on content analysis of 63 development RCTs and 4 years of participant observation, I provide a rich description of the diverse set of actors and the transnational organizational effort required to implement development RCTs and maintain their “scientific status.” Particularly, I investigate the boundary work that proponents of RCTs—also known as randomistas—do to differentiate the purposes and merits of testing development projects from doing them, as a way to bypass the political and ethical problems presented by adopting the experimental method with foreign aid beneficiaries in poor countries. Although randomistas have been mostly successful in differentiating RCTs from the projects evaluated, I also examine cases where they were not able to do so, as a means to highlight the controversies associated with implementing RCTs in international development.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154964/1/bjos12723_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154964/2/bjos12723.pd

    Ultrathin Oxide Films by Atomic Layer Deposition on Graphene

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    In this paper, a method is presented to create and characterize mechanically robust, free standing, ultrathin, oxide films with controlled, nanometer-scale thickness using Atomic Layer Deposition (ALD) on graphene. Aluminum oxide films were deposited onto suspended graphene membranes using ALD. Subsequent etching of the graphene left pure aluminum oxide films only a few atoms in thickness. A pressurized blister test was used to determine that these ultrathin films have a Young's modulus of 154 \pm 13 GPa. This Young's modulus is comparable to much thicker alumina ALD films. This behavior indicates that these ultrathin two-dimensional films have excellent mechanical integrity. The films are also impermeable to standard gases suggesting they are pinhole-free. These continuous ultrathin films are expected to enable new applications in fields such as thin film coatings, membranes and flexible electronics.Comment: Nano Letters (just accepted

    Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene

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    Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state

    First limits on the 21 cm power spectrum during the Epoch of X-ray heating

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    We present first results from radio observations with the Murchison Widefield Array seeking to constrain the power spectrum of 21 cm brightness temperature fluctuations between the redshifts of 11.6 and 17.9 (113 and 75 MHz). 3 h of observations were conducted over two nights with significantly different levels of ionospheric activity. We use these data to assess the impact of systematic errors at low frequency, including the ionosphere and radio-frequency interference, on a power spectrum measurement. We find that after the 1–3 h of integration presented here, our measurements at the Murchison Radio Observatory are not limited by RFI, even within the FM band, and that the ionosphere does not appear to affect the level of power in the modes that we expect to be sensitive to cosmology. Power spectrum detections, inconsistent with noise, due to fine spectral structure imprinted on the foregrounds by reflections in the signal-chain, occupy the spatial Fourier modes where we would otherwise be most sensitive to the cosmological signal. We are able to reduce this contamination using calibration solutions derived from autocorrelations so that we achieve an sensitivity of 104 mK on comoving scales k ~< 0.5 h Mpc−1. This represents the first upper limits on the 21 cm power spectrum fluctuations at redshifts 12~< z ~< 18 but is still limited by calibration systematics. While calibration improvements may allow us to further remove this contamination, our results emphasize that future experiments should consider carefully the existence of and their ability to calibrate out any spectral structure within the EoR window

    Landholder Typologies Used in the Development of Natural Resource Management Programs in Australia - A Review

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    This article reviews the literature on the identification of landholder typologies that can be used to assist the design and delivery of natural resource management (NRM) programs. Australian researchers have developed typologies of landholders based on a variety of criteria. The rationale for developing landholder typologies is first discussed before reviewing the various approaches that have been used by Australian researchers and comparing their findings. The methods employed have differed according to the theories used to guide the research and the 'clients' or 'sponsors' of the research. The landholder types they describe, however, have a number of similarities. These similarities suggest that the studies have identified the same fundamental divisions in the rural community, and that it may be possible to integrate landholder typologies for a variety of NRM and non-NRM applications. It is concluded that further research could usefully investigate whether concepts of social class or sub-cultures may be appropriate to define and describe the variations in landholder types

    Worms take to the slo lane: a perspective on the mode of action of emodepside

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    The cyclo-octapdepsipeptide anthelmintic emodepside exerts a profound paralysis on parasitic and free-living nematodes. The neuromuscular junction is a significant determinant of this effect. Pharmacological and electrophysiological analyses in the parasitic nematode Ascaris suum have resolved that emodepside elicits a hyperpolarisation of body wall muscle, which is dependent on extracellular calcium and the efflux of potassium ions. The molecular basis for emodepside’s action has been investigated in forward genetic screens in the free-living nematode Caenorhabditis elegans. Two screens for emodepside resistance, totalling 20,000 genomes, identified several mutants of slo-1, which encodes a calcium-activated potassium channel homologous to mammalian BK channels. Slo-1 null mutants are more than 1000-fold less sensitive to emodepside than wild-type C. elegans and tissue-specific expression studies show emodepside acts on SLO-1 in neurons regulating feeding and motility as well as acting on SLO-1 in body wall muscle. These genetic data, combined with physiological measurements in C. elegans and the earlier physiological analyses on A. suum, define a pivotal role for SLO-1 in the mode of action of emodepside. Additional signalling pathways have emerged as determinants of emodepside’s mode of action through biochemical and hypothesis-driven approaches. Mutant analyses of these pathways suggest a modulatory role for each of them in emodepside’s mode of action; however, they impart much more modest changes in the sensitivity to emodepside than mutations in slo-1. Taken together these studies identify SLO-1 as the major determinant of emodepside’s anthelmintic activity. Structural information on the BK channels has advanced significantly in the last 2 years. Therefore, we rationalise this possibility by suggesting a model that speculates on the nature of the emodepside pharmacophore within the calcium-activated potassium channels
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