An Experimental and Computational Study of Effects of Microtubule Stabilization on T-Cell Polarity

T-killer cells eliminate infected and cancerous cells with precision by positioning their centrosome near the interface (immunological synapse) with the target cell. The mechanism of centrosome positioning has remained controversial, in particular the role of microtubule dynamics in it. We re-examined the issue in the experimental model of Jurkat cells presented with a T cell receptor-binding artificial substrate, which permits controlled stimulation and reproducible measurements. Neither 1-µM taxol nor 100-nM nocodazole inhibited the centrosome positioning at the “synapse” with the biomimetic substrate. At the same time, in micromolar taxol but not in nanomolar nocodazole the centrosome adopted a distinct peripheral rather than the normally central position within the synapse. This effect was reproduced in a computational energy-minimization model that assumed no microtubule dynamics, but only a taxol-induced increase in the length of the microtubules. Together, the experimental and computational results indicate that microtubule dynamics are not essential for the centrosome positioning, but that the fit of the microtubule array in the deformed body of the conjugated T cell is a major factor. The possibility of modulating the T-cell centrosome position with well-studied drugs and of predicting their effects in silico appears attractive for designing anti-cancer and antiviral therapies

A Model for the Interplay of Receptor Recycling and Receptor-Mediated Contact in T Cells

Orientation of organelles inside T cells (TC) toward antigen-presenting cells (APC) ensures that the immune response is properly directed, but the orientation mechanisms remain largely unknown. Structural dynamics of TC are coupled to dynamics of T-cell receptor (TCR), which recognizes antigen on the APC surface. Engagement of the TCR triggers its internalization followed by delayed polarized recycling to the plasma membrane through the submembrane recycling compartment (RC), which organelle shares intracellular location with the TC effector apparatus. TCR engagement also triggers TC-APC interface expansion enabling further receptor engagement. To analyze the interplay of the cell-cell contact and receptor dynamics, we constructed a new numerical model. The new model displays the experimentally observed selective stabilization of the contact initiated next to the RC, and only transient formation of contact diametrically opposed to the RC. In the general case wherein the TC-APC contact is initiated in an arbitrary orientation to the RC, the modeling predicts that the contact dynamics and receptor recycling can interact, resulting effectively in migration of the contact to the TC surface domain adjacent to the submembrane RC. Using three-dimensional live-cell confocal microscopy, we obtain data consistent with this unexpected behavior. We conclude that a TC can stabilize its contact with an APC by aligning it with the polarized intracellular traffic of TCR. The results also suggest that the orientation of TC organelles, such as the RC and the effector apparatus, toward the APC can be achieved without any intracellular translocation of the organelles

Sucrose in the concentrated solution or the supercooled “state” : a review of caramelisation reactions and physical behaviour

Sucrose is probably one of the most studied molecules by food scientists, since it plays an important role as an ingredient or preserving agent in many formulations and technological processes. When sucrose is present in a product with a concentration near or greater than the saturation point—i.e. in the supercooled state—it possesses high potentialities for the food industry in areas as different as pastry industry, dairy and frozen desserts or films and coatings production. This paper presents a review on critical issues and research on highly concentrated sucrose solutions—mainly, on sucrose thermal degradation and relaxation behaviour in such solutions. The reviewed works allow identifying several issues with great potential for contributing to significant advances in Food Science and Technology.Authors are grateful for the valuable discussions with Teresa S. Brandao and Rosiane Lopes da Cunha during this research. Author M. A. C. Quintas acknowledges the financial support of her research by FCT grant SFRH/BPD/41715/2007

Environmental Control on Biotic Development in Siberia (Verkhoyansk Region) and Neighbouring Areas During Permian-Triassic Large Igneous Province Activity

We propose an updated ammonoid zonation for the Permian-Triassic boundary succession (the lower Nekuchan Formation) in the Verkhoyansk region of Siberia: (1) Otoceras concavum zone (uppermost Changhsingian); (2) Otoceras boreale zone (lowermost Induan); (3) Tompophiceras morpheous zone (lower Induan); and (4) Wordieoceras decipiens zone (lower Induan). The Tompophiceras pascoei zone, previously defined between the Otoceras boreale and Tompophiceras morpheous zones, is removed in our scheme. Instead of this the Tompophiceras pascoei epibole zone is proposed for the lower part of the Tompophiceras morpheous zone. New and previously published nitrogen isotope records are interpreted as responses to climatic fluctuations in the middle to higher palaeolatitudes of Northeastern Asia and these suggest a relatively cool climatic regime for the Boreal Superrealm; however the trend towards warming across the Permian-Triassic boundary transition is also seen. The evolutionary development and geographical differentiation of otoceratid ammonoids and associated groups are considered. It is likely that the Boreal Superrealm was their main refugium, where otocerid, dzhulfitid and some other ammonoids survived the major biotic crisis at the end of the Permian. The similarity of ontogenetic development of suture lines of Otoceras woodwardi Griesbach and O. boreale Spath gives some grounds for suggesting a monophyletic origin of the genus Otoceras, having bipolar distribution