The role of ceramide synthase 2 in sphingosine-1-phosphate-mediated thymic egress

A key element for effective adaptive immunity against invading pathogens is an everchanging peripheral TCR repertoire, which requires the constant release of newly formed T cells from the thymus. The process of thymic egress into the circulation is of chemotactic nature and is mediated by a soluble gradient of the lipid mediator sphingosine-1- phosphate (S1P), which results from low S1P levels in the thymic interstitium, but high S1P levels at the thymic exit sites and in the blood. Despite its importance for peripheral T cell homeostasis, the exact architecture of the thymic S1P gradient, as well as the underlying mechanisms, which maintain the spatial differences in S1P concentration are incompletely understood. In the present study, we investigated if ceramide synthase 2 (CERS2), as regulator of the S1P precursor sphingosine, is involved in the maintenance of the thymic S1P gradient. We found that CERS2 -deficient mice not only exhibited increased amounts of sphingosine, but also elevated levels of S1P within the thymic parenchyma, in the plasma and in RBCs, which resulted in a robust distortion of the S1P gradient between thymus and blood. Consistently, thymic egress was impaired in CERS2 -deficient mice, indicated by a selective accumulation of egress-competent mature SP thymocytes in the thymus and a corresponding T cell lymphopenia in the periphery. We, therefore, concluded that the CERS2-dependent regulation of sphingosine is an important mechanism to facilitate ef- ficient thymic egress of newly formed T cells into the periphery, as it prevents aberrant S1P synthesis by the sphingosine kinases (SPHKs) and thus stabilizes the chemoattractive S1P gradient between thymus and blood. CERS2 is ubiquitously expressed in the hematopoietic and non-hematopoietic cells of the thymus. However, we observed that neither the exclusive ablation of CERS2 in hematopoietic cells, nor the specific absence of CERS2 in thymic stromal cells could phenocopy the impaired S1P-dependent thymic egress, which was observed in CERS2 -deficient mice. These results indicate that CERS2 shapes the thymic S1P gradient not by regulating S1P production in the thymus itself, but in extrathymic non-hematopoietic cells and thus exclusively by limiting the levels of S1P in the circulation. Based on our CERS2 expression data and the current understanding how S1P levels in blood are regulated, we hypothesize that vascular endothelial cells are the most promising cell type, in which CERS2 might be required to compete with the SPHKs to limit the production and secretion of S1P into the plasma. Taken together, our study establishes for the first time a requirement of CERS2 for S1P gradient regulation between thymus and blood. Thus, we advance the understanding how egress from primary lymphoid organs and peripheral lymphocyte homeostasis are regulated in vivo. Consequently, CERS2 might be a promising pharmacological target to treat autoimmune diseases or other immunological disorders by manipulating lymphocyte trafficking

The Deltoid Curve and Triangle Transformations

Deltoid curves appear as consequences of certain procedures in triangle geometry. The best known of these is the construction based on Simson lines, described by Steiner. This is carefully related, in this article, to a less known construction. The standard deltoid in the complex plane and its tangent lines are principle objects of study in this report. It is known that each point in the interior of this curve is the orthocenter of a triangle with distinct vertices on the unit circle, whose product is one. (If instead the point is on the deltoid, then at least two of the vertices coalesce, resulting in a degenerate triangle.) When the vertices are all raised to some specified integer power, a new (possibly degenerate) triangle results. By varying the triangle, one may thus consider the map taking the original triangle's orthocenter to the resulting triangle's orthocenter. Such maps are the other principle objects of study here. The points that are mapped to the deltoid lie on easily described curves. By varying the power involved in the map, a pleasing family of curves results, which includes a trifolium curve. The points that are mapped instead to the origin are described as the points of intersection of certain tangents to the deltoid

Related Problems in Spherical and Solid Geometry

A problem that is simple to state in the context of spherical geometry, and that seems rather interesting, appears to have been unexamined to date in the mathematical literature. The problem can also be recast as a problem in the real projective plane. The problem on the sphere involves four great circles and their intersections. A substantial claim is made concerning this problem, and subsequently proved by relating the spherical problem to a compelling problem in solid geometry. This latter problem essentially concerns relationships between the angles of a tetrahedron, and has practical applications, particularly in connection with the Perspective 3-Point (Pose) Problem.Comment: 8 pages, 4 figure

"Hierarchical routing in sensor networks using κ-dominating sets "

Michael Q. Rieck is an associate professor at Drake University in Des Moines, Iowa, USA. He holds a Ph. D. in mathematics from the University of South Florida. His primary research interests are in the areas of camera tracking and ad hoc wireless networks. He has also published results in the areas of triangle geometry, discrete mathematics, linear algebra, finite fields and association schemes.For a connected graph, representing a sensor network, distributed algorithms for the Set Covering Problem can be employed to construct reasonably small subsets of the nodes, called k-SPR sets. Such a set can serve as a virtual backbone to facilitate shortest path routing, as introduced in [4] and [14]. When employed in a hierarchical fashion, together with a hybrid (partly proactive, partly reactive) strategy, the κ-SPR set methods become highly scalable, resulting in guaranteed minimal path routing, with comparatively little overhead. © Springer-Verlag Berlin Heidelberg 2005

Posibles consecuencias del cambio climático global en bosques de Lago Puelo

p.79-87Se caracteriza topoclimáticamente los habitats del bosque mixto de coihue (Nothofagus dom beyi) y ciprés (Austrocedrus chilensis), del mixto con especies valdivianas y del de lenga (Nothofagus pumilio) en el Parque Nacional y Reserva Estricta Lago Puelo. Se analiza la posible consecuencia del cambio climático en la distribución y composición de dichos bosques. De mantenerse las tendencias que en la actualidad se observan para la temperatura y la precipitación, el clima en el año 2030 sería más húmedo, más frío en el invierno y más caluroso en el verano. La vegetación debería sufrir cambios para alcanzar un nuevo equilibrio, el cual tentativamente favorecería a la lenga y a especies higrófilas como Pilgerodendron uviferum, Fitzroya cupressoides, Lama apiculata y Myrceugenia exsucca

Curvature Filtrations for Graph Generative Model Evaluation

Graph generative model evaluation necessitates understanding differences between graphs on the distributional level. This entails being able to harness salient attributes of graphs in an efficient manner. Curvature constitutes one such property of graphs, and has recently started to prove useful in characterising graphs. Its expressive properties, stability, and practical utility in model evaluation remain largely unexplored, however. We combine graph curvature descriptors with emerging methods from topological data analysis to obtain robust, expressive descriptors for evaluating graph generative models