Staphylococcal Superantigen (TSST-1) Mutant Analysis Reveals that T Cell Activation Is Required for Biological Effects in the Rabbit Including the Cytokine Storm

Staphylococcal superantigens (sAgs), such as toxic shock syndrome toxin 1 (TSST-1), induce massive cytokine production, which may result in toxic shock syndrome (TSS) and sepsis. Recently, we reported that in vitro studies in human peripheral blood mononuclear cells (PBMC) do not reflect the immunological situation of the host, because after exposure to superantigens (sAgs) in vivo, mononuclear cells (MNC) leave the circulation and migrate to organs, e.g., the spleen, liver and lung. Our experimental model of choice is the rabbit because it is comparable to humans in its sensitivity to sAg. T cell activation has been assessed by lymphocyte proliferation and IL-2 gene expression after in vivo challenge with TSST-1 and the mutant antigens; expression of the genes of proinflammatory cytokines were taken as indicators for the inflammatory reaction after the combined treatment with TSST-1 and LPS. The question as to whether the biological activities of TSST-1, e.g., lymphocyte extravasation, toxicity and increased sensitivity to LPS, are mediated by T cell activation or activation by MHC II-only, are unresolved and results are contradictory. We have addressed this question by studying these reactions in vivo, with two TSST-1 mutants: one mutated at the MHC binding site (G31R) with reduced MHC binding with residual activity still present, and the other at the T cell binding site (H135A) with no residual function detectable. Here, we report that the mutant G31R induced all the biological effects of the wild type sAg, while the mutant with non-functional TCR binding did not retain any of the toxic effects, proving the pivotal role of T cells in this system

Signal regulatory protein alpha (SIRPα) regulates the homeostasis of CD103⁺CD11b⁺ DCs in the intestinal lamina propria

Signal regulatory protein alpha (SIRP alpha/CD172a) is a conserved transmembrane protein thought to play an inhibitory role in immune function by binding the ubiquitous ligand CD47. SIRP alpha expression has been used to identify dendritic cell subsets across species and here we examined its expression and function on intestinal DCs in mice. Normal mucosa contains four subsets of DCs based on their expression of CD103 and CD11b and three of these express SIRP alpha. However, loss of SIRP alpha signaling in mice leads to a selective reduction in the CD103(+)CD11b(+) subset of DCs in the small intestine, colon, and amongmigratory DCs in the mesenteric lymph node. In parallel, these mice have reduced numbers of T(H)17 cells in steady-state intestinal mucosa, and a defective T(H)17 response to Citrobacter infection. Identical results were obtained in CD47KO mice. DC precursors from SIRP alpha mutant mice had an enhanced ability to generate CD103(+)CD11b(+) DCs in vivo, but CD103(+)CD11b(+) DCs from mutant mice were more prone to die by apoptosis. These data show a previously unappreciated and crucial role for SIRP alpha in the homeostasis of CD103(+)CD11b(+) DCs in the intestine, as well as providing further evidence that this subset of DCs is critical for the development of mucosal T(H)17 responses

Immunoreactivity of CD99 in Non-Hodgkin's Lymphoma: Unexpected Frequent Expression in ALK-positive Anaplastic Large Cell Lymphoma

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified

Laser melting manufacturing of large elements of lunar regolith simulant for paving on the Moon

The next steps for the expansion of the human presence in the solar system will be taken on the Moon. However, due to the low lunar gravity, the suspended dust generated when lunar rovers move across the lunar soil is a significant risk for lunar missions as it can affect the systems of the exploration vehicles. One solution to mitigate this problem is the construction of roads and landing pads on the Moon. In addition, to increase the sustainability of future lunar missions, in-situ resource utilization (ISRU) techniques must be developed. In this paper, the use of concentrated light for paving on the Moon by melting the lunar regolith is investigated. As a substitute of the concentrated sunlight, a high-power CO2 laser is used in the experiments. With this set-up, a maximum laser spot diameter of 100 mm can be achieved, which translates in high thicknesses of the consolidated layers. Furthermore, the lunar regolith simulant EAC-1A is used as a substitute of the actual lunar soil. At the end of the study, large samples (approximately 250 × 250 mm) with interlocking capabilities were fabricated by melting the lunar simulant with the laser directly on the powder bed. Large areas of lunar soil can be covered with these samples and serve as roads and landing pads, decreasing the propagation of lunar dust. These manufactured samples were analysed regarding their mineralogical composition, internal structure and mechanical properties

Introducing EDEN ISS - A European project on advancing plant cultivation technologies and operations

Plant cultivation in large-scale closed environments is challenging and several key technologies necessary for space-based plant production are not yet space-qualified or remain in early stages of development. The EDEN ISS project foresees development and demonstration of higher plant cultivation technologies, suitable for future deployment on the International Space Station and from a long-term perspective, within Moon and Mars habitats. The EDEN ISS consortium will design and test essential plant cultivation technologies using an International Standard Payload Rack form factor cultivation system for potential testing on-board the International Space Station. Furthermore, a Future Exploration Greenhouse will be designed with respect to future planetary bio-regenerative life support system deployments. The technologies will be tested in a laboratory environment as well as at the highly-isolated German Antarctic Neumayer Station III. A small and mobile container-sized test facility will be built in order to provide realistic mass flow relationships. In addition to technology development and validation, food safety and plant handling procedures will be developed. This paper describes the goals and objectives of EDEN ISS and the different project phases and milestones. Furthermore, the project consortium will be introduced and the role of each partner within the project is explained

Association of CD99 short and long forms with MHC class I, MHC class II and tetraspanin CD81 and recruitment into immunological synapses

<p>Abstract</p> <p>Background</p> <p>CD99, a leukocyte surface glycoprotein, is broadly expressed in many cell types. On the cell surface, CD99 is expressed as two distinct isoforms, a long form and a short form. CD99 has been demonstrated to play a key role in several biological processes, including the regulation of T cell activation. However, the molecular mechanisms by which CD99 participates in such processes are unclear. As CD99 contains a short cytoplasmic tail, it is unlikely that CD99 itself takes part in its multi-functions. Association of CD99 with other membrane proteins has been suggested to be necessary for exerting its functions.</p> <p>Results</p> <p>In this study, we analyzed the association of CD99 with other cell surface molecules involved in T cell activation. We demonstrate the association of MHC class I, MHC class II and tetraspanin CD81 with CD99 molecules on the cell surface. Association of CD99 with its partners was observed for both isoforms. In addition, we determined that CD99 is a lipid raft-associated membrane protein and is recruited into the immunologic synapse during T cell activation. The implication of CD99 on T cell activation was investigated. Inhibition of anti-CD3 induced T cell proliferation by an anti-CD99 monoclonal antibody was observed.</p> <p>Conclusions</p> <p>We provide evidence that CD99 directly interact and form the complex with the MHC class I and II, and tetraspanin CD81, and is functionally linked to the formation of the immunologic synapse. Upon T cell activation, CD99 engagement can inhibit T cell proliferation. We speculate that the CD99-MHC-CD81 complex is a tetraspanin web that plays an important role in T cell activation.</p

Ernährungsphysiologische Bewertung und Optimierung von Frühstückscerealien für die Zielgruppe der Kinder im Alter von 7 bis 10 Jahren

Das Frühstück gilt insbesondere für Kinder als die wichtigste Mahlzeit des Tages und wird trotz allem am Häufigsten ausgelassen. Damit Kinder und auch Erwachsene von den gesundheitlichen Vorteilen einer regelmäßigen ausgewogenen Frühstücksmahlzeit profitieren können, ist die Lebensmittelauswahl entscheidend. Ziel dieser Arbeit ist die ernährungsphysiologische Bewertung der Nährwertprofile von 27 Frühstückscerealien anhand der D-A-CH Referenzwerte für die Nährstoffzufuhr (2015) für Kinder zwischen 7 und 10 Jahren, sowie das Herausarbeiten von Unterschieden zwischen Knusper- und Flockencerealien hinsichtlich ihrer Nährwertprofile. Die Datenanalyse erfolgte mittels Microsoft Excel 2016 (Microsoft, Richmond, WA, USA). Die errechneten Energie- und Nährstoffwerte pro Portion Cerealien, zubereitet mit unter-schiedlichen Milchsorten bzw. -alternativen, wurden mit den für jeden Nährstoff errechneten minimalen bzw. maximalen Referenzwert verglichen. Die Ergebnisse zeigen nur geringe Unterschiede der beiden Cerealien-Gruppen hinsichtlich ihres Energie- und Kohlenhydratgehalts. Flockencerealien schnitten bezüglich ihres Gehalts an Fett, gesättigten Fettsäuren, Zucker, Ballaststoffen, Protein und Salz durchschnittlich besser ab als die Produkte der Gruppe Knuspercerealien. Die empfohlene Zufuhr von 25 Prozent des Richtwertes bzw. der Empfehlung der Tageszufuhr an Energie und Nährstoffen wurde in der Gruppe der Mädchen bei mehr Produkten überschritten als bei den Jungs. Besonders bei den Risikonährstoffen Zucker und gesättigte Fettsäuren als auch bei den Ballaststoffen wurde die 25% Marke in der Gruppe der Mädchen häufiger überschritten. Auf Basis der Ergebnisse der ernährungsphysiologischen Bewertung der am Markt verfügbaren Produkte wurden Rezepturvorschläge für drei Flockencerealien mit Frucht-/Gemüse- oder Kakao-/Nussanteil sowie einem reinem Flockenmix erarbeitet. Die Berechnungen erfolgten mit Hilfe der Nährwertdatenbank BLS 3.02. Das Müsli „Apfel-Karotte“ verfügte in der Gruppe der drei neu entwickelten Produkte über den höchsten Ballaststoffgehalt, den höchsten Eiweißgehalt, den geringsten Fettgehalt und den niedrigsten Gehalt an gesättigten Fettsäuren. Der Flockenmix schnitt innerhalb der drei optimierten Produkte hinsichtlich Zucker- und Salzgehalt am besten ab. Der Flockenmix verfügt innerhalb der neu entwickelten Produkte über den höchsten Kohlenhydratgehalt, den geringsten Zuckergehalt und den geringsten Salzgehalt. Eine Flockenmischung ist als Basismüsli zu empfehlen und kann hervorragend mittels frischem saisonalen oder tiefgefrorenem Obst ergänzt werden.Breakfast is often considered the most important meal of the day and in spite the most commonly omitted one. In order to profit from the various health benefits of a regularly consumed breakfast, the choice of food is crucial. The aim of this thesis is the assessment of the nutritional profiles of 27 breakfast cereals based on the D-A-CH reference values (2015) for energy and nutrient intake for children aged between 7 and 10 years. In Addition, differences between crisp cereals and cereal flakes in terms of their nutritional profiles are determined. Data analysis was done using Excel 2016 (Microsoft, Richmond, WA, USA). The calculated energy and nutrient values per serving cereal, prepared with different milks or milk alternatives, were compared with the minimum and maximum reference value for each nutrient. The results show only minor differences between the two cereal groups regarding their energy and carbohydrate content. Cereal flakes outperform better regarding their content of fat, saturated fatty acids, sugar, dietary fiber, protein and salt compared to crisp cereals. The recommended breakfast intake of 25% of the reference value of daily intake is exceeded by more products with girls compared to boys. Regarding sugar, saturated fatty acid and fiber content, the 25% mark is exceeded more often in the girls group. Based on the results of the nutritional assessment, recipe proposals have been drafted for three different cereal flakes with either different cereals, fruits/vegetables or cocoa/nut ingredients. Calculations were done based on the nutritional database BLS 3.02. Regarding fat, fatty acid, protein and fiber content, the new developed breakfast cereal „apple-carrot” performed best within the three optimized products. Regarding sugar and salt content, the new flake mixture has the best nutritional profile. A flake mixture served with fresh seasonal or frozen fruits can be recommended as an optimal meal for breakfast

EDEN ISS: HUMAN FACTORS AND SUSTAINABILITY FOR SPACE AND EARTH ANALOGUE

In light of upcoming plans for human Moon/Mars missions, the German Aerospace Center (DLR) and its partners are developing a greenhouse to be tested at the German Neumayer station III in Antarctica: the EDEN ISS project. One critical component of future human exploration of unknown worlds will be the supply of edible food for crewmembers. Thus, developing innovations for the cultivation of food in closed-loop systems will become essential for future missions. EDEN ISS focuses on ground demonstration of plant cultivation technologies and their application in Space. It develops safe food production for use on board the International Space Station (ISS) and for future human Space exploration vehicles and planetary outposts. After an introduction on sustainability and the relationship with the EDEN ISS project, this paper deals with research into a range of challenges regarding the improvement and optimization of the greenhouse project’s safety and performance in terms of human-system interaction. The main points are: 1. Human factors for safety and performance 2. Analysis of the main challenges of the EDEN ISS project (with a long-term focus on applicability to future Space-based plant production systems) 3. Human factors implementation proposals The focus is on operator interaction, tackled from the human factors perspective and applying a holistic approach. In other words, the operator’s needs are investigated with regard to psychological, physical, socio-cultural, environmental, and operational factors that need to be taken into account

From ice to space: a greenhouse design for Moon or Mars based on a prototype deployed in Antarctica

The future of human space exploration is aimed at long-term missions to Moon and Mars. Currently, plans are elaborated by NASA, ESA, CNSA and others for a return to the lunar environment within the next decade as an intermediate step towards the goal of reaching the surface of Mars. For sustenance and crew comfort the crew of such long-duration missions should be provided with fresh food on the lunar or Martian surface. Due to the associated power demand, the required resources and technological complexity, this is a major challenge for this kind of missions. To continuously provide fresh food without the need for cargo transfer from Earth towards Moon or Mars an on-site greenhouse system is required, producing the fresh food in situ. The associated effort and cost for all resources to be transported to the base of operation prohibit any waste of resources, requiring a system operating in a (nearly) closed loop. Developing and validating a prototype for an effective and efficient greenhouse, labeled future exploration greenhouse (FEG) for space exploration has been the goal of the EDEN ISS project, funded by the EU, in the past 4 years. This paper shows the results of a design elaboration of the FEG into a greenhouse for planetary deployment on Moon or Mars. Guided by lessons learned from operating the FEG in Antarctica for one year and based on assumptions concerning the mission scenario, e.g. assuming an existing base infrastructure on-site, the presented design incorporates a plant growth area which is more than a factor of two larger than the prototype. The total mass of the cylindrical system, including equipment required during launch, transfer and landing, is about 19 mT, fitting into a Falcon 9 launcher. The versatile design is compatible with a wide variety of mission scenarios, e.g. ESA’s Moon Village, and currently public mission plans