71 research outputs found
A mobile endocytic network connects clathrin-independent receptor endocytosis to recycling and promotes T cell activation
No full textThis file contains raw data of publication by E.B. Compeer et al. Nature Communications 2018. (link will be updated when paper is published online)
Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia
No full textAntiplatelet-antibody-producing B cells play a key role immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand(CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in ITP
Activation-induced thrombospondin-4 works with thrombospondin-1 to build cytotoxic supramolecular attack particles
No full textCytotoxic attack particles released by CTLs and NK cells include diverse phospholipid membrane and glycoprotein encapsulated entities that contribute to target cell killing. Supramolecular attack particles (SMAPs) are one type of particle characterized by a cytotoxic core enriched in granzymes and perforin surrounded by a proteinaceous shell including thrombospondin (TSP)-1. TSP-4 was also detected in bulk analysis of SMAPs released by CTLs; however, it has not been investigated whether TSP-4 contributes to distinct SMAP types or the same SMAP type as TSP-1 and, if in the same type of SMAP, whether TSP-4 and TSP-1 cooperate or compete. Here, we observed that TSP-4 expression increased upon CD8+ T cell activation while, surprisingly, TSP-1 was down-regulated. Correlative Light and Electron Microscopy and Stimulated Emission Depletion microscopy localized TSP-4 and TSP-1 in SMAP-containing multicore granules. Superresolution dSTORM revealed that TSP-4 and TSP-1 are usually enriched in the same SMAPs while particles with single-positive shells are rare. Retention Using Selective Hooks assays showed that TSP-4 localizes to the lytic granules faster than TSP-1 and promotes its accumulation therein. TSP-4 contributed to direct CTL-mediated killing, as previously shown for TSP-1. TSP-4 and TSP-1 were both required for latent SMAP-mediated cell killing, in which released SMAPs kill targets after removal of the CTLs. Of note, we found that chronic lymphocytic leukemia (CLL) cell culture supernatants suppressed expression of TSP-4 in CTL and latent SMAP-mediated killing. These results identify TSP-4 as a functionally important component of SMAPs and suggest that SMAPs may be targeted for immune suppression by CLL
A new concept fiber positioner: Exploring the posibilities of an alternative r-theta design
No full textLarge multi-object spectroscopy telescopes measure the light from millions of stars and galaxies for the use in astronomical studies. One part of these telescopes is the fiber positioner, where a few thousand of optical fibers need to be individually positioned very accurately. The problem with current fiber positioners is the small patrol area, the long production times and the light loss due to the incorrect movement of the tip. The goal of this research is to design a new type of positioner which solves the mentioned problems; large patrol area, fast production and reduction of light loss. The final design is an r-theta design with one rotating motor and a displacement mechanism to move the fiber horizontally over the focal plane. The design is based on the best suitable straight line mechanism from the Reuleaux collection: the Scott-Russell linkage. Flexures are used in the final design. This eliminates backlash and slip-stick effects in therefore improves the accuracy. An experiment with a scale model has been done to show that an exact horizontal positioning with the fiber exactly orthogonal is possible with this design. By adjusting two parameters in the design, the movement and the angle between the horizontal and the fiber can be adjusted. This means an exact movement can be finetuned in order to reduce light loss. The flexure based displacement system is monolithic and can be made by laser cutting. This reduces the production and assembly time of the system drastically. The design meets the patrol area requirement and shows large potential to increase this area up to an estimated 4 times the pitch. In order to validate the remaining requirements of this very promising design, additional experiments with a real scale fully functional prototype is needed.Mechanical Engineerin
Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis
No full textGerminal center (GC) B cells undergo proliferation at very high rates in a hypoxic microenvironment but the cellular processes driving this are incompletely understood. Here we show that the mitochondria of GC B cells are highly dynamic, with significantly upregulated transcription and translation rates associated with the activity of transcription factor A, mitochondrial (TFAM). TFAM, while also necessary for normal B cell development, is required for entry of activated GC precursor B cells into the germinal center reaction; deletion of Tfam significantly impairs GC formation, function and output. Loss of TFAM in B cells compromises the actin cytoskeleton and impairs cellular motility of GC B cells in response to chemokine signaling, leading to their spatial disorganization. We show that B cell lymphoma substantially increases mitochondrial translation and that deletion of Tfam in B cells is protective against the development of lymphoma in a c-Myc transgenic mouse model. Finally, we show that pharmacological inhibition of mitochondrial transcription and translation inhibits growth of GC-derived human lymphoma cells and induces similar defects in the actin cytoskeleton
Suction Grasp Pose Planning Using Self-supervision and Transfer Learning
No full textPlanning grasp poses for a robot on unknown objects in cluttered environments is still an open problem. Recent research suggests that deep learning technique is a promising approach to plan grasp poses on unknown objects in cluttered environments. In this field, three types of data are used for training: (a) human labeled data; (b) synthetic data; (c) real robot data. Each of them has different properties in terms of the cost of collection and label accuracy. Recent approaches solely use a single type of data to train a model. The problem of such a methodology is that human labeled data is inaccurate and costly, synthetic data is scalable but inaccurate, and real robot data is accurate but costly. In this paper, we use the method of combining synthetic data and real robot data to train a Grasp Quality Convolution Neural Network (GQ-CNN). We collect a real robot dataset of 10000 datapoints without human-annotation, by running a UR5 equipped with a pneumatic suction gripper, with an algorithmic supervisor. We use this dataset to fine-tune a GQ-CNN model. We evaluate models both by classifying collected data and running physical robot grasping experiments. We use 50 unknown objects with prismatic and complex shapes for testing. Our method achieves 100% grasp success rate on these objects, and results suggest that the fine-tuned model learns the diameter and the great suction force of the suction cup.Mechanical Engineerin
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