Untersuchungen zur genetischen Variabilität der Chemokinrezeptoren CCR7, CXCR4 und CXCR5

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Phylogeny of "Sphecidae" (Hymenoptera: Apoidea) based on molecular data

Die Grabwespen (Sphecidae sensu Bohart & Menke 1976; Sphecidae sensu lato in neueren, phylogenetischen Arbeiten), zu denen nach Day (1984) und späteren Autoren auch die Heterogynaidae zählen, umfassen derzeit 266 Gattungen mit 9559 beschriebene Arten (Pulawski 2006). Zusammen mit den Bienen (= Apiformes nach Michener 2000, bzw. Anthophila nach Engel 2005) bilden die Grabwespen ein gut begründetes Monophylum, das nach Michener (1986) den Namen Apoidea trägt und eine der drei Hauptlinien innerhalb der aculeaten Hymenoptera ist. Die Monophylie der aculeaten Hymenoptera, der Apoidea sowie die der Bienen ist jeweils gut begründet (z.B. Brothers 1975, Königsmann 1978, Lomholdt 1982, Alexander 1992, Brothers & Carpenter 1993). Anders verhält es sich mit den Grabwespen. Neben der phylogenetischen Untersuchung von Brothers & (1993), die die Monophylie der Grabwespen unterstützt, haben andere morphologische als auch molekularsystematische Analysen starken Zweifel an dieser Hypothese aufkommen lassen (z.B. Königsmann 1978, Lomholdt 1982, Alexander 1992, Prentice 1998, Melo 1999, Ohl & Bleidorn 2006).Sequences from the nuclear long-wavelength-rhodopsin and the mitochondrial cytochrom-c-oxidase (subunit I) from different representatives of the Apoidea, with special emphasis on digger wasps (Sphecidae sensu lat), were analysed using maximum parsimony, maximum likelihood and Baysian inference methods. Compared with previous phylogenetic studies based on morphology, the results of the molecular analyses are controversial but correspond in the absence of support for the Sphecidae s. l (sensu Bohart & Menke). The relationships within the Sphecidae sensu stricto correspond largely with recent morphological studies. There is circumstantial evidence that the Ampulicidae and Sphecidae s. str. together form a monophyletic group, whereas the relationships within this taxon are still uncertain. Although there is no evidence for a definitive phylogenetic position of the Heterogynaidae; it can be excluded that they are the sistertaxon to all other Apoidea. Instead, they are probably a derived group within the Crabronidae. In conflict to the majority of current morphological studies, the molecular analyses provide no support for the Crabronidae and Bembicinae. Some molecular analyses imply a close relationship between Philanthinae and bees

Defect-free assembly of 2D clusters of more than 100 single-atom quantum systems

We demonstrate the defect-free assembly of versatile target patterns of up 111 neutral atoms, building on a 361-site subset of a micro-optical architecture that readily provides thousands of sites for single-atom quantum systems. By performing multiple assembly cycles in rapid succession, we drastically increase achievable structure sizes and success probabilities. We implement repeated target pattern reconstruction after atom loss and deterministic transport of partial atom clusters necessary for distributing entanglement in large-scale systems. This technique will propel assembled-atom architectures beyond the threshold of quantum advantage and into a regime with abundant applications in quantum sensing and metrology, Rydberg-state mediated quantum simulation, and error-corrected quantum computation

The role of grain boundaries in low-temperature plasticity of olivine revealed by nanoindentation

The rheological properties of olivine influence large-scale, long-term deformation processes on rocky planets. Studies of the deformation of olivine at low temperatures and high stresses have emphasized the importance of a grain-size effect impacting yield stress. Laboratory studies indicate that aggregates with finer grains are stronger than those with coarser grains. However, the specific interactions between intracrystalline defects and grain boundaries leading to this effect in olivine remain unresolved. In this study, to directly observe and quantify the mechanical properties of olivine grain boundaries, we conduct nanoindentation tests on well characterized bicrystals. Specifically, we perform room-temperature spherical and Berkovich nanoindentation tests on a subgrain boundary (13°, [100]/(016)) and a high-angle grain boundary (60°, [100]/(011)). These tests reveal that plasticity is easier to initiate if the high-angle grain boundary is within the deformation volume, whereas the subgrain boundary does not impact the initiation of plasticity. Additionally, the high-angle grain boundary acts as a barrier to slip transmission, whereas the subgrain boundary does not interact with dislocations in a measurable manner. We suggest that the distribution of grain-boundary types in olivine-rich rocks might play a role in generating local differences in mechanical behavior during deformation

Thymic T Cell Development and Progenitor Localization Depend on CCR7

T cell differentiation in the adult thymus depends on sequential interactions between lymphoid progenitors and stromal cells found in distinct regions of the cortex and medulla. Therefore, migration of T cell progenitors through distinct stromal environments seems to be a crucial process regulating differentiation and homeostasis inside the thymus

Chemokine Receptor CCR9 Contributes to the Localization of Plasma Cells to the Small Intestine

Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA+ PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA+ PCs express high levels of CCR9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR9-deficient IgA+ PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine

Genetic variants of chemokine receptor CCR7 in patients with systemic lupus erythematosus, Sjogren's syndrome and systemic sclerosis

<p>Abstract</p> <p>Background</p> <p>The chemokine receptor CCR7 is a key organizer of the immune system. Gene targeting in mice revealed that Ccr7-deficient animals are severely impaired in the induction of central and peripheral tolerance. Due to these defects, Ccr7-deficient mice spontaneously develop multi-organ autoimmunity showing symptoms similar to those observed in humans suffering from connective tissue autoimmune diseases. However, it is unknown whether mutations of <it>CCR7 </it>are linked to autoimmunity in humans.</p> <p>Results</p> <p>DNA samples were collected from 160 patients suffering from connective tissue autoimmune disease (Sjogren's syndrome, n = 40; systemic lupus erythematosus, SLE, n = 20 and systemic sclerosis, n = 100) and 40 health subjects (n = 40). All participants in this study were of German descent. Samples were screened for single nucleotide polymorphisms (SNP) by sequencing the coding region of the <it>CCR7 </it>gene as well asthe exon flaking intron sites and parts of the regions encoding for the 5'- and 3'-UTR. <it>CCR7 </it>variants were rare. We identified six different sequence variants, which occurred in heterozygosis. The identified SNP were observed at position -60 C/T (observed 1x), +6,476 A/G (7x), +6,555 C/T (15x), +6,560 C/T (6x), +10,440 A/G (3x) and +11,475 C/A (1x). Four of these variants (+6,476 A/G, +6,555 C/T, +6,560 C/T and +10,440 A/G) display allelic frequencies between 1% and 5 % and were present in both patients and control groups. The variants +6,476 A/G, +6,555 C/T, +6,560 C/T are located in the intron 2, while the +10,440 A/G variant corresponds to a silent mutation in exon 3. The variants -60 C/T and +11,475 C/A which are located at the 5'-UTR and 3-UTR respectively, display allelic frequencies below 1%. No correlation between these variants and the autoimmune diseases investigated could be observed. However, reporter gene expression assay demonstrated that the mutation at the -60 C/T position in homozygosis leads to reduced luciferase activity.</p> <p>Conclusion</p> <p>These results suggest that variants of <it>CCR7 </it>gene occur at an extremely low frequency in the German population and that neither Sjogren's syndrome, systemic lupus erythematosus, nor systemic sclerosis are associated with these variants. Nevertheless, the decreased luciferase activity observed in cells transfected with the promoter region bearing the -60 C/T mutation suggests that this <it>CCR7 </it>variant could potentially lead to increased susceptibility to autoimmunity.</p

Cooperating Mechanisms of CXCR5 and CCR7 in Development and Organization of Secondary Lymphoid Organs

Homeostatic chemokines participate in the development of secondary lymphoid organs and later on in the functional organization of these tissues. The development of lymph nodes (LNs) and Peyer's patches depends on the recruitment of CD3− CD4+ interleukin (IL)-7Rαhi cells to sites of future organ development. CD3− CD4+ IL-7Rαhi cells express the chemokine receptor CXCR5 and might be attracted by its ligand CXCL13, which is secreted by mesenchymal cells. Mesenchymal cells also secrete CCL19, a ligand for CCR7, yet it is not clear whether CCR7 and CCL19 are important for secondary lymphoid organ development. Analyzing CXCR5−/− CCR7−/− double deficient mice we now show that these mice lack all examined peripheral LNs suggesting a profound role for both receptors in secondary lymphoid organ development. We demonstrate that CD3− CD4+ IL-7Rαhi cells express CXCR5 as well as CCR7 indicating that both receptors cooperate during an early step of secondary lymphoid organ development. Furthermore, CXCR5−/− CCR7−/− mice display a severely disturbed architecture of mesenteric LN and spleen. Due to an impaired migration of B cells into the white pulp, CXCR5−/− CCR7−/− mice fail to develop B cell follicles but show small clusters of unorganized lymphocytes in the spleen. These data demonstrate a cooperative function of CXCR5 and CCR7 in lymphoid organ organogenesis and organization

Regulatory T cells interfere with the development of bronchus-associated lymphoid tissue

Presence and extent of bronchus-associated lymphoid tissue (BALT) is subject to considerable variations between species and is only occasionally observed in lungs of mice. Here we demonstrate that mice deficient for the chemokine receptor CCR7 regularly develop highly organized BALT. These structures were not present at birth but were detectable from day 5 onwards. Analyzing CCR7−/−/wild-type bone marrow chimeras, we demonstrate that the development of BALT is caused by alterations of the hematopoietic system in CCR7-deficient mice. These observations together with the finding that CCR7-deficient mice posses dramatically reduced numbers of regulatory T cells (T reg cells) in the lung-draining bronchial lymph node suggest that BALT formation might be caused by disabled in situ function of T reg cells. Indeed, although adoptive transfer of wild-type T reg cells to CCR7-deficient recipients resulted in a profound reduction of BALT formation, neither naive wild-type T cells nor T reg cells from CCR7−/− donors impair BALT generation. Furthermore, we provide evidence that CCR7-deficient T reg cells, although strongly impaired in homing to peripheral lymph nodes, are fully effective in vitro. Thus our data reveal a CCR7-dependent homing of T reg cells to peripheral lymph nodes in conjunction with a role for these cells in controlling BALT formation