1,264 research outputs found

    Elucidating different pattern of immunoregulation in BALB/c and C57BL/6 mice and their F1 progeny

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    © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .Helminths are large multicellular parasites that infect one quarter of the human population. To prolong their survival, helminths suppress the immune responses of their hosts. Strongyloides ratti delays its expulsion from the gut by induction of regulatory circuits in a mouse strain-specific manner: depletion of Foxp3+ regulatory T cells (Treg) improves the anti-S. ratti immunity in BALB/c but not in C57BL/6 mice. In the current study we compare the hierarchy of immunoregulatory pathways in BALB/c, C57BL/6 mice and their F1 progeny (BALB/c × C57BL/6). Using multicolor flow cytometry, we show that S. ratti induces a distinct pattern of inhibitory checkpoint receptors by Foxp3+ Treg and Foxp3- T cells. Intensity of expression was highest in C57BL/6 and lowest in BALB/c mice, while the F1 cross had an intermediate phenotype or resembled BALB/c mice. Treg subsets expanded during infection in all three mouse strains. Similar to BALB/c mice, depletion of Treg reduced intestinal parasite burden and increased mucosal mast cell activation in S. ratti-infected F1 mice. Our data indicate that Treg dominate the regulation of immune responses in BALB/c and F1 mice, while multiple regulatory layers exist in C57BL/6 mice that may compensate for the absence of Treg.Open Access funding enabled and organized by Projekt DEAL.info:eu-repo/semantics/publishedVersio

    Multiple Approaches to Investigate the Transport and Activity-Dependent Release of BDNF and Their Application in Neurogenetic Disorders

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    Studies utilizing genetic and pharmacological manipulations in rodent models and neuronal cultures have revealed myriad roles of brain-derived neurotrophic factor (BDNF). Currently, this knowledge of BDNF function is being translated into improvement strategies for several debilitating neurological disorders in which BDNF abnormalities play a prominent role. Common among the BDNF-related disorders are irregular trafficking and release of mature BDNF (mBDNF) and/or its prodomain predecessor, proBDNF. Thus, investigating the conditions required for proper trafficking and release of BDNF is an essential step toward understanding and potentially improving these neurological disorders. This paper will provide examples of disorders related to BDNF release and serve as a review of the techniques being used to study the trafficking and release of BDNF

    Design eines Virtuellen Supportteams.: Konzeptionelle Überlegungen und empirische Befunde zur Entwicklung Fakultät übergreifender virtueller Teams in der IT-Administration einer Hochschule

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    Körperschaften öffentlichen Rechts im Bildungsbereich zeichnen sich durch eine zunehmende Digitalisierung der Geschäftsprozesse aus. Dies trifft auch für Hochschulen zu, wobei die Produktion der Bildung (hier unter dem Begriff eLearning) ein intensiv untersuchtes Themenfeld ist, sowohl betreffen die Lehre selbst (Fischer et al., 2006)) als auch die dafür erforderlichen Services (Neumann, 2006). Weniger intensiv debattiert wird die Betreuung der IT-Administration als Thema der Organisationsentwicklung. ... Beispielhaft anhand des Bereiches Geistes- und Sozialwissenschaften der Technischen Universität Dresden thematisiert der Beitrag die aktuell anstehenden Gestaltungserfordernisse vor dem Hintergrund der Zielestellung, ein virtuelles Serviceteam für die Aufgaben der IT-Administration in Lehre, Forschung und Verwaltung über mehrere Fakultäten hinweg zu konzipieren. ... [Aus: Einleitung

    Two types of functionally distinct Ca2+ stores in hippocampal neurons

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    It is widely assumed that inositol trisphosphate (IP3) and ryanodine (Ry) receptors share the same Ca2+ pool in central mammalian neurons. We now demonstrate that in hippocampal CA1 pyramidal neurons IP3- and Ry-receptors are associated with two functionally distinct intracellular Ca2+ stores, respectively. While the IP3-sensitive Ca2+ store refilling requires Orai2 channels, Ry-sensitive Ca2+ store refilling involves voltage-gated Ca2+ channels (VGCCs). Our findings have direct implications for the understanding of function and plasticity in these central mammalian neurons

    Self-similar shear-thickening behavior in CTAB/NaSal surfactant solutions

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    The effect of salt concentration Cs on the critical shear rate required for the onset of shear thickening and apparent relaxation time of the shear-thickened phase, has been investigated systematically for dilute CTAB/NaSal solutions. Experimental data suggest a self-similar behavior of the critical shear rate and relaxation time as functions of Cs. Specifically, the former ~ Cs^(-6) whereas the latter ~ Cs^(6) such that an effective Weissenberg number for the onset of the shear thickened phase is only weakly dependent on Cs. A procedure has been developed to collapse the apparent shear viscosity versus shear rate data obtained for various values of Cs into a single master curve. The effect of Cs on the elastic modulus and mesh size of the shear-induced gel phase for different surfactant concentrations is discussed. Experiments performed using different flow cells (Couette and cone-and-plate) show that the critical shear rate, relaxation time and the maximum viscosity attained are geometry-independent. The elastic modulus of the gel phase inferred indirectly by employing simplified hydrodynamic instability analysis of a sheared gel-fluid interface is in qualitative agreement with that predicted for an entangled phase of living polymers. A qualitative mechanism that combines the effect of Cs on average micelle length and Debye parameter with shear-induced configurational changes of rod-like micelles is proposed to rationalize the self-similarity of SIS formation.Comment: 27 pages, 17 figure

    IL-33 facilitates rapid expulsion of the parasitic nematode <i>Strongyloides ratti</i> from the intestine via ILC2- and IL-9-driven mast cell activation

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    Parasitic helminths are sensed by the immune system via tissue-derived alarmins that promote the initiation of the appropriate type 2 immune responses. Here we establish the nuclear alarmin cytokine IL-33 as a non-redundant trigger of specifically IL-9-driven and mast cell-mediated immunity to the intestinal parasite Strongyloides ratti. Blockade of endogenous IL-33 using a helminth-derived IL-33 inhibitor elevated intestinal parasite burdens in the context of reduced mast cell activation while stabilization of endogenous IL-33 or application of recombinant IL-33 reciprocally reduced intestinal parasite burdens and increased mast cell activation. Using gene-deficient mice, we show that application of IL-33 triggered rapid mast cell-mediated expulsion of parasites directly in the intestine, independent of the adaptive immune system, basophils, eosinophils or Gr-1+ cells but dependent on functional IL-9 receptor and innate lymphoid cells (ILC). Thereby we connect the described axis of IL-33-mediated ILC2 expansion to the rapid initiation of IL-9-mediated and mast cell-driven intestinal anti-helminth immunity

    Fungal phytochrome chromophore biosynthesis at mitochondria

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    Mitochondria are essential organelles because of their function in energy conservation. Here, we show an involvement of mitochondria in phytochrome-dependent light sensing in fungi. Phytochrome photoreceptors are found in plants, bacteria, and fungi and contain a linear, heme-derived tetrapyrrole as chromophore. Linearization of heme requires heme oxygenases (HOs) which reside inside chloroplasts in planta. Despite the poor degree of conservation of HOs, we identified two candidates in the fungus Alternaria alternata. Deletion of either one phenocopied phytochrome deletion. The two enzymes had a cooperative effect and physically interacted with phytochrome, suggesting metabolon formation. The metabolon was attached to the surface of mitochondria with a C-terminal anchor (CTA) sequence in HoxA. The CTA was necessary and sufficient for mitochondrial targeting. The affinity of phytochrome apoprotein to HoxA was 57,000-fold higher than the affinity of the holoprotein, suggesting a “kiss-and-go” mechanism for chromophore loading and a function of mitochondria as assembly platforms for functional phytochrome. Hence, two alternative approaches for chromophore biosynthesis and insertion into phytochrome evolved in plants and fungi

    Individually switchable InGaN/GaN nano-LED arrays as highly resolved illumination engines

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    GaN-based light emitting diodes (LEDs) have been shown to effectively operate down to nanoscale dimensions, which allows further downscaling the chip-based LED display technology from micro- to nanoscale. This brings up the question of what resolution limit of the illumination pattern can be obtained. We show two different approaches to achieve individually switchable nano-LED arrays. We evaluated both designs in terms of near-field spot size and optical crosstalk between neighboring pixels by using finite difference time domain (FDTD) simulations. The numerical results were compared with the performance data from a fabricated nano-LED array. The outcome underlines the influence of geometry of the LED array and materials used in contact lines on the final illumination spot size and shape

    Impairment of LTD and cerebellar learning by Purkinje cell–specific ablation of cGMP-dependent protein kinase I

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    The molecular basis for cerebellar plasticity and motor learning remains controversial. Cerebellar Purkinje cells (PCs) contain a high concentration of cGMP-dependent protein kinase type I (cGKI). To investigate the function of cGKI in long-term depression (LTD) and cerebellar learning, we have generated conditional knockout mice lacking cGKI selectively in PCs. These cGKI mutants had a normal cerebellar morphology and intact synaptic calcium signaling, but strongly reduced LTD. Interestingly, no defects in general behavior and motor performance could be detected in the LTD-deficient mice, but the mutants exhibited an impaired adaptation of the vestibulo-ocular reflex (VOR). These results indicate that cGKI in PCs is dispensable for general motor coordination, but that it is required for cerebellar LTD and specific forms of motor learning, namely the adaptation of the VOR
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