20 research outputs found
Modelling of electrode-plasma interactions in Pulsed Plasma Thrusters
No full textElectric propulsion is generally characterized by higher specific impulse than traditional chemical rockets, which gives them propellant saving benefits. These have been applied in deep-space missions and micro-satellites. A Pulsed Plasma Thruster consists of two electrodes around a block of teflon. A pulsed discharge ablates the teflon and ionizes the vapor. This plasma forms a current bridge between the electrodes which is accelerated outwards by the self-induced magnetic field, producing thrust. The current research project has developed and used a 1D model to investigate the current bridge with a focus on the plasma electrode interaction. The influence of electron temperature and density, cathode temperature, voltage, geometry and propellant type on the current density and magnetic field has been explored. The influence of thermionic electron emissions on the current-voltage characteristic has been demonstrated.Aerospace Engineerin
РОЛЬ ОБРАЗОВАТЕЛЬНЫХ УЧРЕЖДЕНИЙ В САМОАКТУАЛИЗАЦИИ ЛИЧНОСТИ УЧАЩИХСЯ
No full textThe article is devoted to the problem of selfactualization at the early stages of development; that is, the infant and child periods. When they speak about self-actualization, specialists of the humanistic direction in psychology they refer more to the adult generation. Therefore, the author sought in their theories about indications of self-actualization features in the early stages of development, and found many of them. Furthermore, the article deals with the role of the educational institutions and their staff in the development of self-actualization of their students.В статье рассматривается роль образовательных учреждений в самоактуализации учащихся. Освещаются отдельные подходы представителей гуманистического направления касающиеся проблемы самоактуализации личности. Рассматривается роль образовательных учреждений в самовыражении школьников и студентов
TMED10 regulates SHH packaing and secretion in EVs and subsequent signalling activity
No full textInternational audienceThe secretion of the morphogen Sonic Hedgehog (SHH) plays a vital role in embryonic brain development in vertebrates. Numerous studies have demonstrated that SHH acts on target cells at a distance from SHH-producing cells via transport in extracellular vesicles (EVs). Previously published work from our lab demonstrated that SHH is packaged and secreted in a distinct subtype of EVs known as ART-EVs due to their unique protein signature of AXL, Rab18 and TMED10. However, the molecular mechanisms that govern the intracellular transport of SHH and its subsequent secretion in ART-EVs is still poorly understood. Here, we employed the retention using selective hooks (RUSH) system to show that newly-synthesized SHH is trafficked through the classical biosynthetic secretory pathway, using TMED10 as an ER cargo receptor for efficient ER-to-Golgi transport. Moreover, silencing of TMED10 leads to a decreased trafficking of SHH to the cell surface, while neosynthesized transferrin receptor (TfR) transport was independent of TMED10. As a consequence, we observed decreased SHH levels in small EVs (sEV) secreted by TMED10-depleted cells and subsequent reduced SHH signalling activity on receiving cells. Finally, we utilized the Drosophila wing imaginal disc model to demonstrate that the homologue of TMED10, Baiser, participates in Hedgehog (Hh) secretion and signalling in vivo. In conclusion, our work highlights the role of TMED10 in cargo-specific egress from the ER and sheds light on a novel important partner of neosynthesized SHH secretion
Slac2-b Coordinates Extracellular Vesicle Secretion to Regulate Keratinocyte Adhesion and Migration
No full textSlac2-b, also known as exophilin-5, is a Rab27b effector protein with a role in exosome transport and is encoded by the EXPH5 gene. We previously described biallelic loss-of-function mutations in EXPH5 in an autosomal recessive form of epidermolysis bullosa simplex. However, how the loss of Slac2-b expression leads to skin fragility and erosions is unknown. In this study, we demonstrate that keratinocytes (KCs) isolated from two different individuals with mutations in EXPH5 have significant defects in cell‒matrix adhesion. EXPH5-mutant KCs also showed increased perinuclear accumulation and significantly reduced trafficking of CD63+ vesicles. These phenotypes were also seen in Slac2-b‒deficient KCs. This was coincident with a reduction in Rab27a protein expression in Slac2-b‒mutant KCs as well as reduced secretion of extracellular vesicles containing extracellular matrix proteins. Live imaging analysis revealed a strong correlation between CD63+ vesicle trafficking to the plasma membrane and focal adhesion dynamics. These findings support a role for Slac2-b in regulating local focal adhesion dynamics to support effective KC adhesion and provide insight into the underlying pathophysiology of inherited skin blistering.</p
TMED10 mediates the loading of neosynthesised Sonic Hedgehog in COPII vesicles for efficient secretion and signalling
No full textInternational audienceThe morphogen Sonic Hedgehog (SHH) plays an important role in coordinating embryonic development. Short- and long-range SHH signalling occurs through a variety of membrane-associated and membrane-free forms. However, the molecular mechanisms that govern the early events of the trafficking of neosynthesised SHH in mammalian cells are still poorly understood. Here, we employed the retention using selective hooks (RUSH) system to show that newly-synthesised SHH is trafficked through the classical biosynthetic secretory pathway, using TMED10 as an endoplasmic reticulum (ER) cargo receptor for efficient ER-to-Golgi transport and Rab6 vesicles for Golgi-to-cell surface trafficking. TMED10 and SHH colocalized at ER exit sites (ERES), and TMED10 depletion significantly delays SHH loading onto ERES and subsequent exit leading to significant SHH release defects. Finally, we utilised the Drosophila wing imaginal disc model to demonstrate that the homologue of TMED10, Baiser (Bai), participates in Hedgehog (Hh) secretion and signalling in vivo. In conclusion, our work highlights the role of TMED10 in cargo-specific egress from the ER and sheds light on novel important partners of neosynthesised SHH secretion with potential impact on embryonic development
TMED10 regulates SHH packaing and secretion in EVs and subsequent signalling activity
No full textInternational audienceThe secretion of the morphogen Sonic Hedgehog (SHH) plays a vital role in embryonic brain development in vertebrates. Numerous studies have demonstrated that SHH acts on target cells at a distance from SHH-producing cells via transport in extracellular vesicles (EVs). Previously published work from our lab demonstrated that SHH is packaged and secreted in a distinct subtype of EVs known as ART-EVs due to their unique protein signature of AXL, Rab18 and TMED10. However, the molecular mechanisms that govern the intracellular transport of SHH and its subsequent secretion in ART-EVs is still poorly understood. Here, we employed the retention using selective hooks (RUSH) system to show that newly-synthesized SHH is trafficked through the classical biosynthetic secretory pathway, using TMED10 as an ER cargo receptor for efficient ER-to-Golgi transport. Moreover, silencing of TMED10 leads to a decreased trafficking of SHH to the cell surface, while neosynthesized transferrin receptor (TfR) transport was independent of TMED10. As a consequence, we observed decreased SHH levels in small EVs (sEV) secreted by TMED10-depleted cells and subsequent reduced SHH signalling activity on receiving cells. Finally, we utilized the Drosophila wing imaginal disc model to demonstrate that the homologue of TMED10, Baiser, participates in Hedgehog (Hh) secretion and signalling in vivo. In conclusion, our work highlights the role of TMED10 in cargo-specific egress from the ER and sheds light on a novel important partner of neosynthesized SHH secretion
The endoplasmic reticulum as a cradle for virus and extracellular vesicle secretion
No full textInternational audienceExtracellular vesicles (EVs) are small membranous carriers of protein, lipid, and nucleic acid cargoes and play a key role in intercellular communication. Recent work has revealed the previously under-recognized participation of endoplasmic reticulum (ER)-associated proteins (ERAPs) during EV secretion, using pathways reminiscent of viral replication and secretion. Here, we present highlights of the literature involving ER/ERAPs in EV biogenesis and propose mechanistic parallels with ERAPs exploited during viral infections. We propose that ERAPs play an active role in the release of EVs and viral particles, and we present views on whether viruses hijack or enhance pre-existing ERAP-dependent secretory machineries or whether they repurpose ERAPs to create new secretory pathways
A Framework for Evaluating Skyline Queries over Incomplete Data
No full textAbstractResearch interest in skyline queries has been significantly increased over the years, as skyline queries can be utilized in many contemporary applications, such as multi-criteria decision-making system, decision support system, recommendation system, data mining, and personalized systems. Skyline queries return data item that is not dominated by any other data items in all dimensions (attributes). Most of the existing skyline approaches assumed that database is complete and values are present during the skyline process. However, such assumption is not always to be true, particularly in a real world database where values of data item might not be available (missing) in one or more dimensions. Thus, the incompleteness of the data impacts negatively on skyline process due to losing the transitivity property which leads into the issue of cyclic dominance. Therefore, applying skyline technique directly on an incomplete database is prohibitive and might result into exhaustive pairwise comparison. This paper presents an approach that efficiently evaluates skyline queries in incomplete database. The approach aims at reducing the number of pairwise comparisons and shortens the searching space in identifying the skylines. Several experiments have been conducted to demonstrate that our approach outperforms the previous approach through producing a lower number of pairwise comparisons. Furthermore, the result also illustrates that our approach is scalable and efficient
Monitoring the dynamics of exosomes through the tracking of Rab7 partners
No full textExtracellular vesicles (EVs) play a crucial role in cell-cell signaling, and their dysregulation is linked to various pathologies. EVs can originate from the plasma membrane as microvesicles, or form within endosomal compartments that fuse with the plasma membrane, releasing their intraluminal vesicles in the extracellular space as exosomes. However, distinguishing between these two types of EVs is challenging due to their common protein markers, necessitating cumbersome isolation methods. To overcome this limitation, we developed an innovative tool using Rab7-mediated proximity labelling and mass spectrometry. This technological advancement enables the covalent labeling of Rab7 partners allowing the tracking of intracellular and extracellular exosomal cargoes
