64 research outputs found

    On the change of growth and wood constructive substances in Salix Koriyanagi which was grown in different soil moisture conditions

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    textabstractThe cellular interactions that drive the formation and maintenance of the insulating myelin sheath around axons are only partially understood. Leucine-rich glioma-inactivated (LGI) proteins play important roles in nervous system development and mutations in their genes have been associated with epilepsy and amyelination. Their function involves interactions with ADAM22 and ADAM23 cell surface receptors, possibly in apposing membranes, thus attenuating cellular interactions. LGI4-ADAM22 interactions are required for axonal sorting and myelination in the developing peripheral nervous system (PNS). Functional analysis revealed that, despite their high homology and affinity for ADAM22, LGI proteins are functionally distinct. To dissect the key residues in LGI proteins required for coordinating axonal sorting and myelination in the developing PNS, we adopted a phylogenetic and computational approach and demonstrate that the mechanism of action of LGI4 depends on a cluster of three amino acids on the outer surface of the LGI4 protein, thus providing a structural basis for the mechanistic differences in LGI protein function in nervous system development and evolution

    Genetic control of Schwann cell differentiation

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    Genetic control of Schwann cell differentiation

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    Schwann cellen myelineren axonen onder de invloed van axonale signalen. Het is nog niet volkomen duidelijk welke signalen dat zijn. Ondanks dat zijn er de laatste jaren wel veel intracellulaire regulatoren van het myelinatie programma geïdentificeerd en bestudeerd. Verschillende factoren die een rol spelen tijdens de ontwikkeling van de myelinerende Schwann cel worden in dit proefschrift beschreven. Twee van de belangrijkste factoren zijn Oct-6 en Krox-20. Wanneer een van beide factoren afwezig is tijdens de ontwikkeling dan vindt er geen myelinatie plaats in de Krox-20 knock-out muis en in de Oct-6 knock-out muis uiteindelijk wel, maar met een flinke vertraging. Omdat er in de Oct-6 mutant uiteindelijk alsnog myelinatie plaatsvindt is er gezocht naar eventuele ander factoren die daar verantwoordelijk voor zouden kunnen zijn. Het blijkt nu als Brn-2 samen met Oct-6 afwezig is tijdens de ontwikkeling van de zenuwen dat dan ook in dit geval geen myelinatie meer optreedt. Wanneer nu overexpressie van Brn-2 in de Oct-6 mutant tot stand wordt gebracht blijkt dat myelinatie van de axonen op bijna het normale niveau plaats vindt. Naast deze Oct-6 en Krox-20 mutanten is er ook nog een natuurlijke mutant clawpaw. Deze mutant vertoont net als de Oct-6 mutant een ernstige vertraging in de myelinatie van de axonen. De natuurlijke mutant clawpaw heeft een afwijkende Lgi4 expressie. Dit kan een indicatie zijn dat Lgi4 betrokken is bij het myelinatie proces in de Schwann cel

    The acid-base flow battery:Tradeoffs between energy density, efficiency, and stability

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    The deployment of renewable energy inevitably relies on environmentally friendly energy storage systems. An acid-base flow battery (ABFB) uses the principle of bipolar membrane (BPM) (reverse) electrodialysis to store excess electrical energy in abundant and benign materials (sodium chloride and water). However, this technology suffers from high energy losses due to undesired ion crossover through the membranes. In this study, we investigate the contribution of the membrane type as well as the different ions in the battery, and identify the major causes for this crossover and thus capacity losses. We also study the ion crossover under different ABFB operating conditions (pH gradient, current density, and used ions). The main losses are due to the diffusion-driven acid crossover through the BPM, facilitated by the small size and high mobility of protons. Operating at higher pH gradients leads to a higher energy density, but the ABFB stability is compromised due to the higher driving force for co-ion crossover. Running the ABFB at higher current densities does not alter the diffusion-driven crossover, but does make it relatively less important than the desired electromigration. However, this goes at the expense of higher ohmic losses and thus lower voltaic efficiency. Switching to divalent ions (such as sulfate) successfully prevents acid crossover through the BPM, but increases the membranes resistance, thus decreasing the voltaic efficiency.</p

    Functional phylogenetic analysis of LGI proteins identifies an interaction motif crucial for myelination

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    The cellular interactions that drive the formation and maintenance of the insulating myelin sheath around axons are only partially understood. Leucine-rich glioma-inactivated (LGI) proteins play important roles in nervous system development and mutations in their genes have been associated with epilepsy and amyelination. Their function involves interactions with ADAM22 and ADAM23 cell surface receptors, possibly in apposing membranes, thus attenuating cellular interactions. LGI4-ADAM22 interactions are required for axonal sorting and myelination in the developing peripheral nervous system (PNS). Functional analysis revealed that, despite their high homology and affinity for ADAM22, LGI proteins are functionally distinct. To dissect the key residues in LGI proteins required for coordinating axonal sorting and myelination in the developing PNS, we adopted a phylogenetic and computational approach and demonstrate that the mechanism of action of LGI4 depends on a cluster of three amino acids on the outer surface of the LGI4 protein, thus providing a structural basis for the mechanistic differences in LGI protein function in nervous system development and evolution

    Functional phylogenetic analysis of LGI proteins identifies an interaction motif crucial for myelination

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    The cellular interactions that drive the formation and maintenance of the insulating myelin sheath around axons are only partially understood. Leucine-rich glioma-inactivated (LGI) proteins play important roles in nervous system development and mutations in their genes have been associated with epilepsy and amyelination. Their function involves interactions with ADAM22 and ADAM23 cell surface receptors, possibly in apposing membranes, thus attenuating cellular interactions. LGI4-ADAM22 interactions are required for axonal sorting and myelination in the developing peripheral nervous system (PNS). Functional analysis revealed that, despite their high homology and affinity for ADAM22, LGI proteins are functionally distinct. To dissect the key residues in LGI proteins required for coordinating axonal sorting and myelination in the developing PNS, we adopted a phylogenetic and computational approach and demonstrate that the mechanism of action of LGI4 depends on a cluster of three amino acids on the outer surface of the LGI4 protein, thus providing a structural basis for the mechanistic differences in LGI protein function in nervous system development and evolution

    A reference map of murine cardiac transcription factor chromatin occupancy identifies dynamic and conserved enhancers

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    Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering developmental transcriptional programs. Here we use biotinylated knockin alleles of seven key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult mouse heart. These maps show that TF occupancy is dynamic between developmental stages and that multiple TFs often collaboratively occupy the same chromatin region through indirect cooperativity. Multi-TF regions exhibit features of functional regulatory elements, including evolutionary conservation, chromatin accessibility, and activity in transcriptional enhancer assays. H3K27ac, a feature of many enhancers, incompletely overlaps multi-TF regions, and multi-TF regions lacking H3K27ac retain conservation and enhancer activity. TEAD1 is a core component of the cardiac transcriptional network, co-occupying cardiac regulatory regions and controlling cardiomyocyte-specific gene functions. Our study provides a resource for deciphering the cardiac transcriptional regulatory network and gaining insights into the molecular mechanisms governing heart development

    Novel Foxo1-dependent transcriptional programs control Treg cell function

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    Regulatory T (T(reg)) cells, characterized by expression of the transcription factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self-destructive immune responses. Foxp3 operates as a late-acting differentiation factor controlling T(reg) cell homeostasis and function, whereas the early T(reg)-cell-lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors. However, whether Foxo proteins act beyond the T(reg)-cell-commitment stage to control T(reg) cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of T(reg )cell function. T(reg) cells express high amounts of Foxo1 and display reduced T-cell-receptor-induced Akt activation, Foxo1 phosphorylation and Foxo1 nuclear exclusion. Mice with T(reg)-cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to that seen in Foxp3-deficient mice, but without the loss of T(reg) cells. Genome-wide analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the pro-inflammatory cytokine Ifng, that do not seem to be directly regulated by Foxp3. These findings show that the evolutionarily ancient Akt-Foxo1 signalling module controls a novel genetic program indispensable for T(reg) cell function
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