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51.
Kremer MC Christiansen F Leiss F Paehler M Knapek S Andlauer TF Förstner F Kloppenburg P Sigrist SJ Tavosanis G 《Current biology : CB》2010,20(21):1938-1944
How does the sensory environment shape circuit organization in higher brain centers? Here we have addressed the dependence on activity of a defined circuit within the mushroom body of adult Drosophila. This is a brain region receiving olfactory information and involved in long-term associative memory formation. The main mushroom body input region, named the calyx, undergoes volumetric changes correlated with alterations of experience. However, the underlying modifications at the cellular level remained unclear. Within the calyx, the clawed dendritic endings of mushroom body Kenyon cells form microglomeruli, distinct synaptic complexes with the presynaptic boutons of olfactory projection neurons. We developed tools for high-resolution imaging of pre- and postsynaptic compartments of defined calycal microglomeruli. Here we show that preventing firing of action potentials or synaptic transmission in a small, identified fraction of projection neurons causes alterations in the size, number, and active zone density of the microglomeruli formed by these neurons. These data provide clear evidence for activity-dependent organization of a circuit within the adult brain of the fly. 相似文献
52.
Fiegel HC Pryymachuk G Rath S Bleiziffer O Beier JP Bruns H Kluth D Metzger R Horch RE Till H Kneser U 《Journal of cellular and molecular medicine》2010,14(1-2):267-274
The use of foetal liver cells (FLC) in the context of hepatic tissue engineering might permit efficient in vitro expansion and cryopreservation in a cell bank. A prerequisite for successful application of bioartificial liver tissue is sufficient initial vascularization. In this study, we evaluated the transplantation of fibrin gel-immobilized FLC in a vascularized arterio-veno-venous (AV)-loop model. FLC were isolated from embryonic/foetal (ED 16) rat livers and were enriched by using magnetic cell sorting (MACS). After cryopreservation, FLC were labelled by pkh-26. Cells were transplanted in a fibrin matrix into a subcutaneous chamber containing a microsurgically created AV-loop in the femoral region of the recipient rat. The chambers were explanted after 14 days. Subcutaneous implants without an AV-loop and cell-free implants served as controls. Fluorescence microscopy of the constructs was used to identify pkh-26+ - donor cells. Characterization was performed by RT-PCR and immunhistology (IH) for CK-18 and CD31. Transplantation of FLC using the AV-loop permitted a neo -tissue formation in the fibrin matrix. A high-density vascularization was observed in the AV-loop constructs as shown by CD31 IH. Viable foetal donor cells were detected which expressed CK-18. FLC can be successfully used for heterotopic transplantation. Fibrin matrix permits rapid blood vessel ingrowth from the AV-loop and supports engraftment of FLC. It is therefore an appropriate environment for hepatocyte transplantation in combination with microsurgical vascularization strategies. Transplantation of fibrin gel-immobilized FLC may be a promising approach for the development of highly vascularized in vivo tissue-engineering-based liver support systems. 相似文献
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Experiments with gummy bears With gelatin in the form of gummy bears, the differences to vegetable gelling agents can be easily demonstrated by simple experiments. How these gummy bears can also be used to produce sustainable labels is shown in this article. The presented experiments and instructions are part of a experiment kit with teaching materials for the implementation of a project week in schools with the topic “sustainability”. 相似文献
55.
Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion 总被引:3,自引:0,他引:3
Rosenstiel P Sina C End C Renner M Lyer S Till A Hellmig S Nikolaus S Fölsch UR Helmke B Autschbach F Schirmacher P Kioschis P Hafner M Poustka A Mollenhauer J Schreiber S 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(12):8203-8211
Mucosal epithelial cell layers are constantly exposed to a complex resident microflora. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by pathogen binding. This report describes the regulation and function of DMBT1 in intestinal epithelial cells, which form the primary immunological barrier for invading pathogens. We report that intestinal epithelial cells up-regulate DMBT1 upon proinflammatory stimuli (e.g., TNF-alpha, LPS). We demonstrate that DMBT1 is a target gene for the intracellular pathogen receptor NOD2 via NF-kappaB activation. DMBT1 is strongly up-regulated in the inflamed intestinal mucosa of Crohn's disease patients with wild-type, but not with mutant NOD2. We show that DMBT1 inhibits cytoinvasion of Salmonella enterica and LPS- and muramyl dipeptide-induced NF-kappaB activation and cytokine secretion in vitro. Thus, DMBT1 may play an important role in the first line of mucosal defense conferring immune exclusion of bacterial cell wall components. Dysregulated intestinal DMBT1 expression due to mutations in the NOD2/CARD15 gene may be part of the complex pathophysiology of barrier dysfunction in Crohn's disease. 相似文献
56.
Beuerle T Theuring C Klewer N Schulz S Hartmann T 《Insect biochemistry and molecular biology》2007,37(1):80-89
Arctiids which as larvae sequester pyrrolizidine alkaloids (PAs) from their food plants are known to synthesize insect-specific PAs by esterifying necine bases derived from plant PAs with necic acids of insect origin. There are two classes of insect PAs, the creatonotines and the callimorphines. The creatonotines contain as necic acids either 2-hydroxy-3-methylbutyric acid (creatonotine A) or 2-hydroxy-3-methylpentanoic acid (creatonotine B). The three known callimorphines contain 2-hydroxy-2-methylbutanoic acid whose hydroxyl group can be either free (deacetylcallimorphine) or acetylated (callimorphine) or propionylated (homocallimorphine). Insect PAs are assumed to play an important role in the recycling of plant derived necine bases and the processing by trans-esterification of PA monoesters that cannot be directly transmitted to the insect's pupal and adult life-stages. The absolute configuration of the insect-specific necic acids was elucidated in the context of the suggested role of the insect PAs as insect-made mimics of plant monoester PAs of the lycopsamine type. For this purpose all needed stereoisomers were synthesized and a gas chromatography-mass spectrometry (GC-MS) method was established that allows the enantioselective separation and assignment of the stereochemistry of all insect specific necic acids as their methyl esters. The method could also be applied to the GC-MS analysis of the intact alkaloids which were hydrolyzed during injection and converted into their methyl esters. Analysis of the creatonotines and callimorphines isolated from the polyphagous arctiids Estigmene acrea and Grammia geneura that were fed with pure PAs and defined PA mixtures revealed the following absolute configuration: the callimorphines and creatonotine A were present in 2'R configuration, whereas creatonotine B was found as mixture of (2'R, 3'S)- and (2'S, 3'S)-stereoisomers. The ratio of 2'S to 2'R was extremely variable ranging from 98% S to 94% R. The cause of the lack of stereospecificity is discussed particularly in respect of a possible epimerization of the hydroxyl group at C-2' in analogy to the known epimerization at C-3' of plant acquired PAs of the lycopsamine type. 相似文献
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Seigo Terawaki Voahirana Camosseto Francesca Prete Till Wenger Alexia Papadopoulos Christiane Rondeau Alexis Combes Christian Rodriguez Rodrigues Thien-Phong Vu Manh Mathieu Fallet Luc English Rodrigo Santamaria Ana R. Soares Tobias Weil Hamida Hammad Michel Desjardins Jean-Pierre Gorvel Manuel A.S. Santos Evelina Gatti Philippe Pierre 《The Journal of cell biology》2015,210(7):1133-1152
Autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain–containing protein 4 (RUFY4) as a positive molecular regulator of macroautophagy in primary dendritic cells (DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in turn actively promote LC3 degradation, Syntaxin 17–positive autophagosome formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen presentation by MHC II and allows host control of Brucella abortus replication in IL-4–treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first molecule characterized to date that promotes autophagy and influences endosome dynamics in a subset of immune cells. 相似文献
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60.
Till Fassbinder Ute Saunders Eva Mickholz Elisabeth Jung Heidemarie Becker Bernhard Schlüter Annett Marita Jacobi 《Arthritis research & therapy》2015,17(1)
IntroductionDisease activity and therapy show an impact on cellular and serological parameters in patients with systemic lupus erythematosus (SLE). This study was performed to compare the influence of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) therapy on these parameters in patients with flaring, organ-threatening disease.MethodsSLE patients currently receiving CYC (n = 20), MMF (n = 25) or no immunosuppressive drugs (n = 22) were compared using a cross-sectional design. Median disease activity and daily corticosteroid dose were similar in these treatment groups. Concurrent medication, organ manifestations, and disease activity were recorded, and cellular and serological parameters were determined by routine diagnostic tests or flow cytometric analysis. In addition follow-up data were obtained from different sets of patients (CYC n = 24; MMF n = 23).ResultsAlthough both drugs showed a significant effect on disease activity and circulating B cell subsets, only MMF reduced circulating plasmablasts and plasma cells as well as circulating free light chains within three months of induction therapy. Neither MMF nor CYC were able to reduce circulating memory B cells. MMF lowered IgA levels more markedly than CYC. We did not observe a significant difference in the reduction of IgG levels or anti-dsDNA antibodies comparing patients receiving MMF or CYC. In contrast to MMF, induction therapy with CYC was associated with a significant increase of circulating CD8+ effector T cells and plasmacytoid dendritic cells (PDCs) after three months.ConclusionsThe results indicate differences between MMF and CYC with regard to the mechanism of action. MMF, but not CYC, treatment leads to a fast and enduring reduction of surrogate markers of B cell activation, such as circulating plasmablasts, plasma cells and free light chains but a comparable rate of hypogammaglobulinemia.