74 research outputs found

    Wavelength-dependent optoacoustic imaging probes for NMDA receptor visualisation

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    The cellular localisation and binding specificity of two NMDAR-targeted near-IR imaging probes has been examined by microscopy, followed by exemplification of MSOT to monitor simulated glutamate bursts in cellulo and a preliminary study in mice observing the signal in the brain

    A reversible state of hypometabolism in a human cellular model of sporadic Parkinson's disease

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    Sporadic Parkinson's Disease (sPD) is a progressive neurodegenerative disorder caused by multiple genetic and environmental factors. Mitochondrial dysfunction is one contributing factor, but its role at different stages of disease progression is not fully understood. Here, we showed that neural precursor cells and dopaminergic neurons derived from induced pluripotent stem cells (hiPSCs) from sPD patients exhibited a hypometabolism. Further analysis based on transcriptomics, proteomics, and metabolomics identified the citric acid cycle, specifically the alpha-ketoglutarate dehydrogenase complex (OGDHC), as bottleneck in sPD metabolism. A follow-up study of the patients approximately 10 years after initial biopsy demonstrated a correlation between OGDHC activity in our cellular model and the disease progression. In addition, the alterations in cellular metabolism observed in our cellular model were restored by interfering with the enhanced SHH signal transduction in sPD. Thus, inhibiting overactive SHH signaling may have potential as neuroprotective therapy during early stages of sPD. Mitochondrial dysfunction is a contributing factor in Parkinson's disease. Here the authors carry out a multilayered omics analysis of Parkinson's disease patient-derived neuronal cells, which reveals a reversible hypometabolism mediated by alpha-ketoglutarate dehydrogenase deficiency, which is correlated with disease progression in the donating patients

    High-Resolution Electron Microscopy of Semiconductor Heterostructures and Nanostructures

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    This chapter briefly describes the fundamentals of high-resolution electron microscopy techniques. In particular, the Peak Pairs approach for strain mapping with atomic column resolution, and a quantitative procedure to extract atomic column compositional information from Z-contrast high-resolution images are presented. It also reviews the structural, compositional, and strain results obtained by conventional and advanced transmission electron microscopy methods on a number of III–V semiconductor nanostructures and heterostructures

    Die Relation der Verhaltenstherapie zu systemischer Therapie und Synergetik

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    Fragt man Therapeutinnen und Therapeuten, was das Gemeinsame bzw. Trennende zwischen systemischer Therapie (im Weiteren: ST), Synergetik und Verhaltenstherapie (im Weiteren: VT) ist, bekommt man annähernd so viele Antworten, wie Therapeuten befragt werden. Das lässt sich auf den individuell unterschiedlichen Ausbildungsstand, auf persönliche Arbeitsstile, konkrete therapeutische Erfahrungen, heterogene Darstellungen in der einschlägigen Literatur zurückführen. Die folgende Abhandlung des Themas muss aus den gleichen Gründen subjektiv bleiben, auch wenn durch zahlreiche Bezüge auf die Literatur eine >>objektive<< Verankerung angestrebt wird. Die Frage wird zuweilen von Patienten und Ausbildungskandidaten gestellt - also sollte man auch versuchen, eine Antwort zu finden

    Volumetric tracking of migratory melanophores during zebrafish development by optoacoustic microscopy.

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    Unveiling mechanisms driving specification, recruitment and regeneration of melanophores is key in understanding melanin-related disorders. This study reports on the applicability of a hybrid focus optoacoustic microscope (HFOAM) for volumetric tracking of migratory melanophores in developing zebrafish. The excellent contrast from highly-absorbing melanin provided by the method is shown to be ideal for label-free dynamic visualization of melanophores in their unperturbed environment. We established safe laser energy levels that enable high-contrast longitudinal tracking of the cells over an extended period of developmental time without causing cell toxicity or pigment bleaching. Owing to its hybrid optical and acoustic resolution, the new imaging technique can be seamlessly applied for noninvasive studies of both optically-transparent larval as well as adult stages of the zebrafish model organism, which is not possible using other optical microscopy methods

    Author Correction: Zebrafish and medaka offer insights into the neurobehavioral correlates of vertebrate magnetoreception (Nature Communications DOI: 10.1038/s41467-018-03090-6).

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    In the original version of this Article, Oryzias latipes was incorrectly spelt Oryzias lapites in the main text and in Fig. 1. These errors have been corrected in both the PDF and HTML versions of the Article

    Zebrafish and medaka offer insights into the neurobehavioral correlates of vertebrate magnetoreception.

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    An impediment to a mechanistic understanding of how some species sense the geomagnetic field ("magnetoreception") is the lack of vertebrate genetic models that exhibit well-characterized magnetoreceptive behavior and are amenable to whole-brain analysis. We investigated the genetic model organisms zebrafish and medaka, whose young stages are transparent and optically accessible. In an unfamiliar environment, adult fish orient according to the directional change of a magnetic field even in darkness. To enable experiments also in juveniles, we applied slowly oscillating magnetic fields, aimed at generating conflicting sensory inputs during exploratory behavior. Medaka (but not zebrafish) increase their locomotor activity in this assay. Complementary brain activity mapping reveals neuronal activation in the lateral hindbrain during magnetic stimulation. These comparative data support magnetoreception in teleosts, provide evidence for a light-independent mechanism, and demonstrate the usefulness of zebrafish and medaka as genetic vertebrate models for studying the biophysical and neuronal mechanisms underlying magnetoreception
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