8 research outputs found

    Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain

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    6 pĂĄginas, 2 figurasReprogramming technology enables the production of neural progenitor cells (NPCs) from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs) differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs) and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs.This study was supported by research funding from the IMF at University Hospital MĂŒnster to GH (I-HA-111219) and from the DFG to TK (SFB-TRR128-B7).Peer reviewe

    Structural member stability verification in the new Part 1‐1 of the second generation of Eurocode 3: Part 2: Member buckling design rules and further innovations

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    This two‐part article gives an overview of the developments of the structural member verification in prEN 1993‐1‐1:2020 ”Eurocode 3: Design of steel structures – part 1‐1: General rules and rules for buildings“, one of the second generation of Eurocodes. These developments were undertaken by Working Group 1 (WG1) of Subcommittee CEN/TC250/SC3 and by Project Team 1 (SC3.PT1) responsible for drafting the new version of EN 1993‐1‐1. In the past, WG1 collected many topics needing improvement, and the systematic review conducted every five years also yielded topics needing further development. Based on this, the current version of EN 1993‐1‐1 has been developed into a new draft version prEN 1993‐1‐1:2020 enhancing ”ease of use“. The technical content of this new draft was laid down at the end of 2019. Many improvements to design rules have been established with respect to structural analysis, resistance of cross‐sections and stability of members. This two‐part article focuses on member stability design rules and deals with the basis for the calibration of partial factors, the introduction of more economic design rules for semi‐compact sections, methods for structural analysis in relation to the appropriate member stability design rules, new design rules for lateral torsional buckling plus other developments and innovations. This second part of the article is dedicated to illustrating the most relevant changes to member buckling design rules.ISSN:1867-0520ISSN:1867-053

    Structural member stability verification in the new Part 1-1 of the second generation of Eurocode 3

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    This two-part article gives an overview of the developments of the structural member verification in prEN 1993-1-1:2020 ”Eurocode 3: Design of steel structures – part 1-1: General rules and rules for buildings“, one of the second generation of Eurocodes. These developments were undertaken by Working Group 1 (WG1) of Subcommittee CEN/TC250/SC3 and by Project Team 1 (SC3.PT1) responsible for drafting the new version of EN 1993-1-1. In the past, WG1 collected many topics needing improvement, and the systematic review conducted every five years also yielded topics needing further development. Based on this, the current version of EN 1993-1-1 has been developed into a new draft version prEN 1993-1-1:2020 enhancing ”ease of use“. The technical content of this new draft was laid down at the end of 2019. Many improvements to design rules have been established with respect to structural analysis, resistance of cross-sections and stability of members. This two-part article focuses on member stability design rules and deals with the basis for the calibration of partial factors, the introduction of more economic design rules for semi-compact sections, methods for structural analysis in relation to the appropriate member stability design rules, new design rules for lateral torsional buckling plus other developments and innovations. This second part of the article is dedicated to illustrating the most relevant changes to member buckling design rules

    Distinct Neurodegenerative Changes in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia Linked to Mutant TAU Protein

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    Frontotemporal dementia (FTD) is a frequent form of early-onset dementia and can be caused by mutations in MAPT encoding the microtubule-associated protein TAU. Because of limited availability of neural cells from patients’ brains, the underlying mechanisms of neurodegeneration in FTD are poorly understood. Here, we derived induced pluripotent stem cells (iPSCs) from individuals with FTD-associated MAPT mutations and differentiated them into mature neurons. Patient iPSC-derived neurons demonstrated pronounced TAU pathology with increased fragmentation and phospho-TAU immunoreactivity, decreased neurite extension, and increased but reversible oxidative stress response to inhibition of mitochondrial respiration. Furthermore, FTD neurons showed an activation of the unfolded protein response, and a transcriptome analysis demonstrated distinct, disease-associated gene expression profiles. These findings indicate distinct neurodegenerative changes in FTD caused by mutant TAU and highlight the unique opportunity to use neurons differentiated from patient-specific iPSCs to identify potential targets for drug screening purposes and therapeutic intervention
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