186 research outputs found

    Studies of Charge Exchange in a High‐Pressure Pulsed Electron Impact Source

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    This is the publisher's version, also available electronically from http://scitation.aip.org/content/aip/journal/jcp/56/3/10.1063/1.1677327.A high pressure pulsed ion source has been used in a time‐of‐flight mass spectrometer in order to study the charge exchangereactions in Ar–H2 and Ar–D2 systems using the ion source in the Čermák mode of operation. As the source was used in a pulsed mode, it was possible to identify the various secondary ions arising from the charge exchangereactions in these systems. Very good agreement has been shown to exist between the experimental results and simple theoretical deductions. Calculations have been made to determine the cross sections for the charge exchangereactions between the various species from the experimental data

    Alzheimer's Risk Gene TREM2 Determines Functional Properties of New Type of Human iPSC-Derived Microglia

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    Microglia are key in the homeostatic well-being of the brain and microglial dysfunction has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Due to the many limitations to study microglia in situ or isolated for large scale drug discovery applications, there is a high need to develop robust and scalable human cellular models of microglia with reliable translatability to the disease. Here, we describe the generation of microglia-like cells from human induced pluripotent stem cells (iPSC) with distinct phenotypes for mechanistic studies in AD. We started out from an established differentiation protocol to generate primitive macrophage precursors mimicking the yolk sac ontogeny of microglia. Subsequently, we tested 36 differentiation conditions for the cells in monoculture where we exposed them to various combinations of media, morphogens, and extracellular matrices. The optimized protocol generated robustly ramified cells expressing key microglial markers. Bulk mRNA sequencing expression profiles revealed that compared to cells obtained in co-culture with neurons, microglia-like cells derived from a monoculture condition upregulate mRNA levels for Triggering Receptor Expressed On Myeloid Cells 2 (TREM2), which is reminiscent to the previously described disease-associated microglia. TREM2 is a risk gene for AD and an important regulator of microglia. The regulatory function of TREM2 in these cells was confirmed by comparing wild type with isogenic TREM2 knock-out iPSC microglia. The TREM2-deficient cells presented with stronger increase in free cytosolic calcium upon stimulation with ATP and ADP, as well as stronger migration towards complement C5a, compared to TREM2 expressing cells. The functional differences were associated with gene expression modulation of key regulators of microglia. In conclusion, we have established and validated a work stream to generate functional human iPSC-derived microglia-like cells by applying a directed and neuronal co-culture independent differentiation towards functional phenotypes in the context of AD. These cells can now be applied to study AD-related disease settings and to perform compound screening and testing for drug discoverySG was supported by the Roche Postdoctoral Fellowship (RPF) program and IP by the Roche Internships for Scientific Exchange (RiSE) progra

    Studien über anorganische Kolloide

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    Dialysatoren

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    Beiträge zur Kenntnis der Tellursäure

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    Ueber das Atomgewicht des Tellurs II

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    Über Bromosalze des Platins

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