1,369 research outputs found

    Überlegungen zum Verhältnis von Raum und Wissen im platonischen Bildbegriff

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    Platon gilt gemeinhin nicht als Freund von Bild und Kunst, insofern diese einer wahren Erkenntnis diametral entgegenstehen. Anhand der Trias von Raum, Wissen und Bild wird aufgezeigt, dass Platon das Verhältnis von Bild und Wissen in mehreren Hinsichten in dezidiert räumlichen Kategorien erörtert, womit sich seine Bildkritik auf den Bereich der skiagraphia einschränken lässt. In einem zweiten Schritt werden Raum und Wissen vor dem Hintergrund von Platons Prinzipienlehre aufeinander bezogen, wobei der strukturellen Parallele von Bild und chôra eine entscheidende Rolle zukommt. Hierdurch ergibt sich, dass – expliziert an Platons Höhlengleichnis – dem Bild eine entscheidende Rolle im Aufstieg zur Erkenntnis zukommen kann. Weiterhin wird im Anschluss an den platonischen Ansatz ein Raumbegriff skizziert, der den Raum über die Kategorie des Sinns zu begreifen sucht

    Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation

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    © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Troetschel, C., Hamzeh, H., Alvarez, L., Pascal, R., Lavryk, F., Boenigk, W., Koerschen, H. G., Mueller, A., Poetsch, A., Rennhack, A., Gui, L., Nicastro, D., Struenker, T., Seifert, R., & Kaupp, U. B. Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation. Embo Journal, 39(4), (2020): e102723, doi:10.15252/embj.2019102723.Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca2+ rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin Arbacia punctulata. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H+, and Ca2+. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.We thank Heike Krause for preparing the manuscript. Financial support by the Deutsche Forschungsgemeinschaft (DFG) via the priority program SPP 1726 “Microswimmers” and the Cluster of Excellence 1023 “ImmunoSensation” is gratefully acknowledged. We thank D. Stoddard for management of the UTSW cryo‐electron microscope facility, which is funded in part by a Cancer Prevention and Research Institute of Texas (CPRIT) Core Facility Award (RP170644). This study was supported by HHS|National Institutes of Health (NIH) grant R01 GM083122 and by CPRIT grant RR140082 to D. Nicastro

    The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision

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    Calcium (Ca2+) plays an important role in the function and health of neurons. In vertebrate cone photoreceptors, Ca2+ controls photoresponse sensitivity, kinetics, and light adaptation. Despite the critical role of Ca2+ in supporting the function and survival of cones, the mechanism for its extrusion from cone outer segments is not well understood. Here, we show that the Na+/Ca2+, K+ exchanger NCKX4 is expressed in zebrafish, mouse, and primate cones. Functional analysis of NCKX4-deficient mouse cones revealed that this exchanger is essential for the wide operating range and high temporal resolution of cone-mediated vision. We show that NCKX4 shapes the cone photoresponse together with the cone-specific NCKX2: NCKX4 acts early to limit response amplitude, while NCKX2 acts late to further accelerate response recovery. The regulation of Ca2+ by NCKX4 in cones is a novel mechanism that supports their ability to function as daytime photoreceptors and promotes their survival

    Unrecognised language teaching: Teaching Australian Curriculum content in remote Aboriginal community schools

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    The case study in this article offers a descriptive account of challenges involved in teaching Australian Curriculum content in the common teaching context in remote communities where an Indigenous language is spoken as the everyday form of communication and students learn English in what is essentially a foreign language setting. An on-theground description of the work of a Primary school teaching team servesto illustrate the language teaching aspect of delivering Australian Curriculum content in areas such as History, Geography and Science. This aspect of the teaching team’s work is underestimated in the curriculum itself and in the guidance provided to teachers, yet is essential for student learning in this context. While the team draws on students’ L1 and early L2 English proficiency abilities to teach curriculum content, this work is not expedited from outside their classroom. An analysis of current curriculum offerings and the teaching team’s approaches finds that they receive little direction for the extensive language planning required. The findings suggest an urgent need for tailor-made curriculum and teacher guidance which better recognise this dual language context. This article canvases different curriculum settings that would alleviate this situation considerably, not only for this teaching team but for others in similar remote schools

    Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism

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    Dihydrotestosterone (DHT) has acute/non-genomic actions in adult mammalian skeletal muscles whose physiological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the acute/non-genomic effects of DHT on amino acid uptake as well as the cellular signal transduction events underlying these actions in mouse fast- and slow-twitch skeletal muscle fibre bundles. 14C-Labelled amino acids were used to investigate the effects of DHT and testosterone (T) on amino acid uptake and pharmacological interventions were used to determine the cellular signal transduction events mediating these actions. While T had no effect on the uptake of isoleucine (Ile) and a-methylaminoisobutyric acid (MeAIB) in both fibre types, DHT increased their uptake in the fast-twitch fibre bundles. This effect was reversed by inhibitors of protein translation, the epidermal growth factor receptor (EGFR), system A, system L, mTOR and MEK. However, it was relatively insensitive to inhibitors of transcription, androgen receptors and PI3K/Akt. Additionally, DHT treatment increased the expression of LAT2 and the phosphorylation of the EGFR in the fast-twitch fibre bundles and that of ERK1/2, RSK1/2 and ATF2 in both fibre types. Also, it decreased the phosphorylation of eEF2 and increased the incorporation of Ile into proteins in both fibre types. Most of these effects were reversed by EGFR and MEK inhibitors. From these findings we suggest that another physiological function of the acute/non-genomic actions of DHT in isolated mammalian skeletal muscle fibres is to stimulate amino acid uptake. This effect is mediated through the EGFR and involves the activation of the MAPK pathway and an increase in LAT2 expression

    Stereoselektive Synthesewege zu (+)-Biotin aus L-Cystein

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    A novel synthesis of (+)-biotin (vitamin H) via a pathway which avoids separation of enantiomers is described. Starting with L-cysteine, the key intermediate 7 is synthesized in four steps without racemization. In a short reaction sequence 7 is converted into 10 or 14 in an overall yield of 40% and 27%, respectively. Both known intermediates are easily transformed into (+)-biotin

    19 Language revitalisation: community and school programs working together

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    Analysis of four PCR/SNaPshot multiplex assays analyzing 52 SNPforID markers

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    The SNPforID consortium identified a panel of 52 SNPs forensic analysis that has been used by several laboratories worldwide. The original analysis of the 52 SNPs was based on a single multiplex reaction followed by two single-base-extension (SBE) reactions each of which was analyzed using capillary electrophoresis. The SBE assays were designed for high throughput genetic analyzers and were difficult to use on the single capillary ABI PRISM 310 Genetic Analyzer and the latest generation 3500 Genetic Analyzer, as sensitivity on the 310 was low and separation of products on the 3500 with POP-7™ was poor. We have modified the original assay and split it into four multiplex reactions, each followed by an SBE assay. These multiplex assays were analyzed using polymer POP-4™ on ABI 310 PRISM® and polymers POP-4™, POP-6™ and POP-7™ on the 3500 Genetic Analyzer. The assays were sensitive and reproducible with input DNA as low as 60 pg using both the ABI 310 and 3500. In addition, we found that POP-6™ was most effective with the 3500, based on the parameters that we assessed, achieving better separation of the small SBE products; this conflicted with the recommended use of POP-7™ by the instrument manufacturer. To support the use of the SNP panel in casework in Malaysia we have created an allele frequency database from 325 individuals, representing the major population groups within Malaysia. Population and forensic parameters were estimated for all populations and its efficacy evaluated using 51 forensic samples from challenging casework

    Proteomics of Brucella

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    Brucella spp. are Gram negative intracellular bacteria responsible for brucellosis, a worldwide distributed zoonosis. A prominent aspect of the Brucella life cycle is its ability to invade, survive and multiply within host cells. Comprehensive approaches, such as proteomics, have aided in unravelling the molecular mechanisms underlying Brucella pathogenesis. Technological and methodological advancements such as increased instrument performance and multiplexed quantification have broadened the range of proteome studies, enabling new and improved analyses, providing deeper and more accurate proteome coverage. Indeed, proteomics has demonstrated its contribution to key research questions in Brucella biology, i.e., immunodominant proteins, host-cell interaction, stress response, antibiotic targets and resistance, protein secretion. Here, we review the proteomics of Brucella with a focus on more recent works and novel findings, ranging from reconfiguration of the intracellular bacterial proteome and studies on proteomic profiles of Brucella infected tissues, to the identification of Brucella extracellular proteins with putative roles in cell signaling and pathogenesis. In conclusion, proteomics has yielded copious new candidates and hypotheses that require future verification. It is expected that proteomics will continue to be an invaluable tool for Brucella and applications will further extend to the currently ill-explored aspects including, among others, protein processing and post-translational modification.Fil: Poetsch, Ansgar. Center For Marine And Molecular Biotechnology; China. Ocean University of China; ChinaFil: Marchesini, Maria Ines. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentin

    Genesis and Classification Considerations of Some Prairie-Formed Soil Profiles From Local Alluvium in Adair County, Iowa

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    Data are presented on three profiles formed under prairie from Late Wisconsin to Recent age local alluvium of moderately fine texture. In the upper 20 inches nitrogen and base saturation values are quite similar to those found for normative upland Brunizems. Below 20 to about 50 inches, nitrogen and base saturation values decrease and increase, respectively, more slowly in the local alluvium-formed soils. It is suggested that the classic ABC soil genesis concept does not apply to the local alluvium-formed soils of this study. Rather, through cumulative effects of new parent material at the surface, this new C was transformed to an Ac horizon (c for cumulative effect), the former A1 was transformed to a Bc horizon, and the former B became a substratum Cc horizon. Soil genesis effects in such cumulative soil genesis systems need further attention, as these soils comprise about one-fourth of the land area of Iowa, are important agriculturally, and an understanding will further knowledge of other soils of Iowa
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