29 research outputs found

    Resolving early mesoderm diversification through single-cell expression profiling.

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    In mammals, specification of the three major germ layers occurs during gastrulation, when cells ingressing through the primitive streak differentiate into the precursor cells of major organ systems. However, the molecular mechanisms underlying this process remain unclear, as numbers of gastrulating cells are very limited. In the mouse embryo at embryonic day 6.5, cells located at the junction between the extra-embryonic region and the epiblast on the posterior side of the embryo undergo an epithelial-to-mesenchymal transition and ingress through the primitive streak. Subsequently, cells migrate, either surrounding the prospective ectoderm contributing to the embryo proper, or into the extra-embryonic region to form the yolk sac, umbilical cord and placenta. Fate mapping has shown that mature tissues such as blood and heart originate from specific regions of the pre-gastrula epiblast, but the plasticity of cells within the embryo and the function of key cell-type-specific transcription factors remain unclear. Here we analyse 1,205 cells from the epiblast and nascent Flk1(+) mesoderm of gastrulating mouse embryos using single-cell RNA sequencing, representing the first transcriptome-wide in vivo view of early mesoderm formation during mammalian gastrulation. Additionally, using knockout mice, we study the function of Tal1, a key haematopoietic transcription factor, and demonstrate, contrary to previous studies performed using retrospective assays, that Tal1 knockout does not immediately bias precursor cells towards a cardiac fate.We thank M. de Bruijn, A. Martinez-Arias, J. Nichols and C. Mulas for discussion, the Cambridge Institute for Medical Research Flow Cytometry facility for their expertise in single-cell index sorting, and S. Lorenz from the Sanger Single Cell Genomics Core for supervising purification of Tal1−/− sequencing libraries. ChIP-seq reads were processed by R. Hannah. Research in the authors’ laboratories is supported by the Medical Research Council, Cancer Research UK, the Biotechnology and Biological Sciences Research Council, Bloodwise, the Leukemia and Lymphoma Society, and the Sanger-EBI Single Cell Centre, and by core support grants from the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute and by core funding from Cancer Research UK and the European Molecular Biology Laboratory. Y.T. was supported by a fellowship from the Japan Society for the Promotion of Science. W.J. is a Wellcome Trust Clinical Research Fellow. A.S. is supported by the Sanger-EBI Single Cell Centre. This work was funded as part of Wellcome Trust Strategic Award 105031/D/14/Z ‘Tracing early mammalian lineage decisions by single-cell genomics’ awarded to W. Reik, S. Teichmann, J. Nichols, B. Simons, T. Voet, S. Srinivas, L. Vallier, B. Göttgens and J. Marioni.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1863

    Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

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    A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

    Evaluating the susceptibility of invasive black rats (Rattusrattus) and house mice (Mus musculus) to brodifacoumas a prelude to rodent eradication on Lord Howe Island

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    The use of anticoagulant rodenticides to eradicate invasive rodents from islands has become a powerful tool to prevent species extinctions and to restore degraded ecosystems. Success is dependent on all targeted individuals consuming rodenticide and dying as a result. Because susceptibility to anticoagulants can vary among rodent populations, it is important when planning an eradication to understand the efficacy of the proposed rodenticide on the target animals, particularly where there has been historic exposure to anticoagulants. The aims of this study were to investigate brodifacoum-susceptibility of black rats Rattus rattus and house mice Mus musculus on Lord Howe Island (LHI), Australia, where an eradication program is being planned. Black rats and house mice were subjected to various dosages of brodifacoum in a series of laboratory feeding trials. The results showed that rats on LHI died after consuming doses of rodenticide within expected ranges (60% died at 0.5 mg kg−1 and 100% died at 0.8 mg kg−1) when exposed to bait for 24 h. Mice, on the other hand, were more tolerant of the rodenticide, with 82% of individuals surviving doses of up to 2.0 mg kg−1 consumed over 24 h and some individuals needing 6.0 mg kg−1 consumed over 4 days to ingest a lethal dose. A laboratory experiment designed to simulate field application showed that all mice tested succumbed to brodifacoum poisoning when given the opportunity to consume sufficient bait (at least 6 days of exposure to toxic bait), although some individuals took 22 days to die. The results of these studies will help inform the Lord Howe Island rodent eradication

    Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

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    Structure-Activity Relations for Neurotransmitter Receptor Agonists and Antagonists

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    Impact of Tillage Methods on Environment, Energy and Economy

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    ISSN 2210-4410, eISBN 9783319990767Soil tillage involves the mechanical manipulation of soils used for crop production. Tillage is done to prepare an optimal seedbed, to loosen compacted soil layers, to control weeds, to increase aeration, to incorporate plant residues into the soil, to facilitate water infiltration and soil moisture storage, and to control soil temperature. Nonetheless, soil tillage is one of the highest energy-consuming, environment-polluting and expensive technological processes in agriculture. Conventional tillage with ploughing is the most widely used practice. Conventional tillage has low efficiency, requires high-powered tractors with high fuel consumption and greenhouse gases emissions. Moreover, the cost of conventional tillage is high, and the influence on the soil structure, degradation, leaching of nutrients and the most fertile soil is negative. Here we review the impact of tillage methods on soil quality, environment and economy. Due to the disadvantages of conventional tillage, sustainable tillage area increases each year by 4-6 million ha worldwide. Under sustainable tillage such as minimal or no-tillage, the total soil surface modified by the wheels of agricultural machinery is 20-40% lower than for conventional tillage. Sustainable tillage preserves better soil physical properties and biological processes. A comparison of tillage methods show that no-tillage has the highest energy efficiency ratio of 14.0, versus 12.4 for deep ploughing. The most expensive tillage operation is deep ploughing. The use of agricultural machinery under sustainable tillage conditions and preparation of soils without using a plough can reduce costs from 25% to 41%, compared with conventional tillageVytauto Didžiojo universitetasŽemės ūkio akademij
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