3,362 research outputs found

    The strange death of number controls in England : paradoxical adventures in higher education market making

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    The paper analyses the impact of a higher education funding mechanism, the 'High Grades' policy, introduced as part of a student number control regime in England that was introduced in 2012/13 and withdrawn after only two years. This marked the end of an experiment in market making based on quality and price within a fixed student number cap. The paper analyses the impact of policy in key areas of institutional behaviour which taken together illustrate why the specific higher education market mechanism failed. The focus will be on two key areas of institutional behaviour which taken together illustrate why the specific higher education market mechanism failed, and how longer term marketisation is affecting the different institution types in the sector in ways inimical to equity and social justice. The two areas are: 1) strategic responses by selective universities (pre-1992s ) to the 'high grades' policy reform and its impact on attempts to protect subject breadth and widening participation (WP); 2) the market pressure felt by post-1992 universities to differentiate themselves from their competitors due to the demands of institutional league tables. These in turn illustrate the ways that longer term marketisation is affecting the different institution types in the sector in ways inimical to autonomy, equity and social justice

    What about nitrogen? Using nitrogen as a carrier gas during the analysis of petroleum biomarkers by gas chromatography mass spectrometry

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    Open access via the Elsevier AgreementPeer reviewedPublisher PD

    Sushi gets serious:the draft genome sequence of the pufferfish Fugu rubripes

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    The publication of the Fugu rubripes draft genome sequence will take this fish from culinary delicacy to potent tool in deciphering the mysteries of human genome function

    2,5-Di-(tert-butyl)-1,4-benzohydroquinone mobilizes inositol 1,4,5-trisphosphate-sensitive and -insensitive Ca2+ stores

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    AbstractIn permcabilized rat hepatocytcs a maximal concentration (25 μM) of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) mobilized 70% of sequestered Ca2+ and a half-maximal effect was produced by 1.7 μM tBuBHQ. Inositol 1,4,5-trisphosphate (Ins(1,4,5) P3) stimulated release of about 40% of the intracellular Ca2+ stores. Combined applications of a range of tBuBHQ concentrations with a maximal concentration of Ins(1,4,5)P3 demonstrated that tBuBHQ has slight selectivity for the Ca2+ transport process of the Ins(1,4,5) P3-sensitive stores. We conclude that the Ins(1,4,5) P3-sensitive stores arc a subset of those sensitive to tBuBHQ and that the latter is therefore unlikely to prove useful as a tool to discriminate Ins(1,4,5) P3-sensitive and -insensitive Ca2+ stores though it may provide opportunities to design more selective agents

    Improved synchronous production of Plasmodium falciparum gametocytes in vitro.

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    The sexual stages of the Plasmodium falciparum life cycle are attractive targets for vaccines and transmission blocking drugs. Difficulties in culturing and obtaining large amounts of sexual stage P. falciparum parasites, particularly early stages, have often limited research progress in this area. We present a new protocol which simplifies the process of stimulating gametocytogenesis leading to improved synchronous gametocyte production. This new method can be adapted to enrich for early stage gametocytes (I and II) with a higher degree of purity than has previously been achieved, using MACS magnetic affinity columns. The protocol described lends itself to large scale culturing and harvesting of synchronous parasites suitable for biochemical assays, northern blots, flow cytometry, microarrays and proteomic analysis

    Revision of Madagascar's Dwarf Lemurs (Cheirogaleidae:Cheirogaleus): Designation of Species, Candidate Species Status and Geographic Boundaries Based on Molecular and Morphological Data

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    The genus Cheirogaleus, the dwarf lemurs, is a radiation of strepsirrhine primates endemic to the island of Madagascar. The dwarf lemurs are taxonomically grouped in the family Cheirogaleidae (Infraorder: Lemuriformes) along with the genera Microcebus, Mirza, Allocebus, and Phaner. The taxonomic history of the genus Cheirogaleus has been controversial since its inception due to a paucity of evidence in support of some proposed species. In this study, we addressed this issue by expanding the geographic breadth of samples by 91 individuals and built upon existing mitochondrial (cytb and COII) and nuclear (FIBA and vWF) DNA datasets to better resolve the phylogeny of Cheirogaleus. The mitochondrial gene fragments D-loop and PAST as well as the CFTR-PAIRB nuclear loci were also sequenced. In agreement with previous genetic studies, numerous deep divergences were resolved in the C. major, C. minor and C. medius lineages. Four of these lineages were segregated as new species, seven were identified as confirmed candidate species, and four were designated as unconfirmed candidate species based on comparative mitochondrial DNA sequence data gleaned from the literature or this study. Additionally, C. thomasi was resurrected. Given the widespread distribution of the genus Cheirogaleus throughout Madagascar, the methodology employed in this study combined all available lines of evidence to standardize investigative procedures in a genus with limited access to type material and a lack of comprehensive sampling across its total distribution. Our results highlighted lineages that likely represent new species and identified localities that may harbor an as-yet undescribed cryptic species diversity pending further field and laboratory work.We are most grateful to the Ahmanson Foundation, the Theodore F. and Claire M. Hubbard Family Foundation, the Primate Action Fund / Conservation International, the Margot Marsh Biodiversity Foundation, and the National Geographic Society, for financial assistance

    Structural and functional conservation of key domains in InsP3 and ryanodine receptors.

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    Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca(2+) channels. In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6 Å) and without (3.0 Å) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-β and IBC-α, identifies two discrete interfaces (α and β) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R and of the ABC domains docked into RyR are remarkably similar. The importance of the α-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations. Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the β-interface and pulling the SD towards the IBC. This reorients an exposed SD loop ('hotspot' (HS) loop) that is essential for InsP(3)R activation. The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease. The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-β or B domain), to gate the pore
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