Lck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement

In spite of a comprehensive understanding of the schematics of T cell receptor (TCR) signaling, the mechanisms regulating compartmentalization of signaling molecules, their transient interactions, and rearrangement of membrane structures initiated upon TCR engagement remain an outstanding problem. These gaps in our knowledge are exemplified by recent data demonstrating that TCR triggering is largely dependent on a preactivated pool of Lck concentrated in T cells in a specific type of membrane microdomains. Our current model posits that in resting T cells all critical components of TCR triggering machinery including TCR/CD3, Lck, Fyn, CD45, PAG, and LAT are associated with distinct types of lipid-based microdomains which represent the smallest structural and functional units of membrane confinement able to negatively control enzymatic activities and substrate availability that is required for the initiation of TCR signaling. In addition, the microdomains based segregation spatially limits the interaction of components of TCR triggering machinery prior to the onset of TCR signaling and allows their rapid communication and signal amplification after TCR engagement, via the process of their coalescence. Microdomains mediated compartmentalization thus represents an essential membrane organizing principle in resting T cells. The integration of these structural and functional aspects of signaling into a unified model of TCR triggering will require a deeper understanding of membrane biology, novel interdisciplinary approaches and the generation of specific reagents. We believe that the fully integrated model of TCR signaling must be based on membrane structural network which provides a proper environment for regulatory processes controlling TCR triggering

Использование барий-стронциевого карбонатита при изготовлении сварочных флюсов на основе техногенных отходов металлургического производства

В данной работе рассмотрена возможность использования барий-стронциевого карбонатита при изготовлении сварочных флюсов на основе шлака производства силикомарганца, а так же на основе ковшевых электросталеплавильных шлаков, образованных при производстве рельсовых марок стали. В серии опытов в лабораторных условиях изготавливали и исследовали различные составы сварочных флюсов, были определены химические составы наплавленного металла, проведен металлографический анализ.In this paper the possibility of using barium-strontium carbonatite in the manufacture of welding fluxes on the basis of slag from the production of silicomanganese, and based on ladle steelmaking slags formed in the production of rail steel grades. In a series of experiments in the laboratory have produced and investigated different compositions of welding fluxes, were determined the chemical compositions of the weld metal metallographic analysis

Age-related prefrontal cortex activation in associative memory: an fNIRS pilot study.

Older adults typically perform more poorly than younger adults in free recall memory tests. This age-related deficit has been linked to decline of brain activation and brain prefrontal lateralization, which may be the result of compensatory mechanisms. In the present pilot study, we investigated the effect of age on prefrontal cortex (PFC) activation during performance of a task that requires memory associations (temporal vs. spatial clustering), using functional Near-Infrared Spectroscopy (fNIRS). Ten younger adults, ten cognitively high-performing older individuals, and ten low-performing older individuals completed a free recall task, where either a temporal or spatial strategy (but not both simultaneously) could be employed to retrieve groups of same-category stimuli, whilst changes in PFC haemodynamics were recorded by means of a 12-channel fNIRS system. The results suggest PFC activation, and right lateralization specific to younger adults. Moreover, age did not affect use of memory organization, given that temporal clustering was preferred over spatial clustering in all groups. These findings are in line with previous literature on the aging brain and on temporal organization of memory. Our results also suggest that the PFC may be specifically involved in memory for temporal associations. Future research may consider whether age-related deficits in temporal organization may be an early sign of PFC pathology and possible neurodegeneration

Plant diversity effects on grassland productivity are robust to both nutrient enrichment and drought

Global change drivers are rapidly altering resource availability and biodiversity. While there is consensus that greater biodiversity increases the functioning of ecosystems, the extent to which biodiversity buffers ecosystem productivity in response to changes in resource availability remains unclear. We use data from 16 grassland experiments across North America and Europe that manipulated plant species richness and one of two essential resources—soil nutrients or water—to assess the direction and strength of the interaction between plant diversity and resource alteration on above-ground productivity and net biodiversity, complementarity, and selection effects. Despite strong increases in productivity with nutrient addition and decreases in productivity with drought, we found that resource alterations did not alter biodiversity–ecosystem functioning relationships. Our results suggest that these relationships are largely determined by increases in complementarity effects along plant species richness gradients. Although nutrient addition reduced complementarity effects at high diversity, this appears to be due to high biomass in monocultures under nutrient enrichment. Our results indicate that diversity and the complementarity of species are important regulators of grassland ecosystem productivity, regardless of changes in other drivers of ecosystem function

Multiple Facets of Biodiversity Drive the Diversity-Stability Relationship

A significant body of evidence has demonstrated that biodiversity stabilizes ecosystem functioning over time in grassland ecosystems. However, the relative importance of different facets of biodiversity underlying the diversity–stability relationship remains unclear. Here we used data from 39 biodiversity experiments and structural equation modeling to investigate the roles of species richness, phylogenetic diversity, and both the diversity and community-weighted mean of functional traits representing the ‘fast–slow’ leaf economics spectrum in driving the diversity–stability relationship. We found that high species richness and phylogenetic diversity stabilize biomass production via enhanced asynchrony. Contrary to our hypothesis, low phylogenetic diversity also enhances ecosystem stability directly, albeit weakly. While the diversity of fast–slow functional traits has a weak effect on ecosystem stability, communities dominated by slow species enhance ecosystem stability by increasing mean biomass production relative to the standard deviation of biomass over time. Our results demonstrate that biodiversity influences ecosystem stability via a variety of facets, thus highlighting a more multicausal relationship than has been previously acknowledged

On the Experimental Analysis of Integral Sliding Modes for Yaw Rate and Sideslip Control of an Electric Vehicle with Multiple Motors

With the advent of electric vehicles with multiple motors, the steady-state and transient cornering responses can be designed and implemented through the continuous torque control of the individual wheels, i.e., torque-vectoring or direct yaw moment control. The literature includes several papers on sliding mode control theory for torque-vectoring, but the experimental investigation is so far limited. More importantly, to the knowledge of the authors, the experimental comparison of direct yaw moment control based on sliding modes and typical controllers used for stability control in production vehicles is missing. This paper aims to reduce this gap by presenting and analyzing an integral sliding mode controller for concurrent yaw rate and sideslip control. A new driving mode, the Enhanced Sport mode, is proposed, inducing sustained high values of sideslip angle, which can be limited to a specified threshold. The system is experimentally assessed on a four-wheel-drive electric vehicle. The performance of the integral sliding mode controller is compared with that of a linear quadratic regulator during step steer tests. The results show that the integral sliding mode controller significantly enhances the tracking performance and yaw damping compared to the more conventional linear quadratic regulator based on an augmented singletrack vehicle model formulation. © 2018, The Korean Society of Automotive Engineers and Springer-Verlag GmbH Germany, part of Springer Natur

Lifespan Extension by Preserving Proliferative Homeostasis in Drosophila

Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs) and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK) signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan

Epigenetická agens indikují expresi MHC glykoproteinů I. třídy na nádorových buňkách a reexpresi dočasně umlčeného znaku u nádorů myeloidního původu

1. lékařská fakultaFirst Faculty of Medicin