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91.
Contact of T lymphocytes with nicotinamide adenine dinucleotide (NAD) or ATP causes cell death that requires expression of purinergic receptor P2X(7) (P2X(7)R). T cell subsets differ in their responses to NAD and ATP, which awaits a mechanistic explanation. Here, we show that sensitivity to ATP correlates with P2X(7)R expression levels in CD4 cells, CD8 cells and CD4(+)CD25(+) cells from both C57BL/6 and BALB/c mice. But P2X(7)R ligands do not only induce cell death but also shedding of CD62L. It is shown here that in CD62L(high) T cells, CD62L shedding correlates with low expression of P2X(7)Rs and lower cell death, whereas in CD62L(low) cells P2X(7)R expression and death are higher. The possibility is therefore investigated that P2X(7)Rs induce T cell activation. Experiments show that spontaneous T cell proliferation is somewhat higher in cells expressing P2X(7)Rs, but this effect we suggest is caused by P2X(7)R expression on accessory cells. 相似文献
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Doehlemann G Wahl R Horst RJ Voll LM Usadel B Poree F Stitt M Pons-Kühnemann J Sonnewald U Kahmann R Kämper J 《The Plant journal : for cell and molecular biology》2008,56(2):181-195
The fungal pathogen Ustilago maydis establishes a biotrophic relationship with its host plant maize (Zea mays). Hallmarks of the disease are large plant tumours in which fungal proliferation occurs. Previous studies suggested that classical defence pathways are not activated. Confocal microscopy, global expression profiling and metabolic profiling now shows that U. maydis is recognized early and triggers defence responses. Many of these early response genes are downregulated at later time points, whereas several genes associated with suppression of cell death are induced. The interplay between fungus and host involves changes in hormone signalling, induction of antioxidant and secondary metabolism, as well as the prevention of source leaf establishment. Our data provide novel insights into the complexity of a biotrophic interaction. 相似文献
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Butyrate reversibly arrests the proliferation of normal and Rous sarcoma virus-infected chicken heart mesenchymal cells 总被引:3,自引:0,他引:3
Sodium butyrate at 5 X 10(-3) M reversibly arrests the proliferation of both normal and RSV-infected chicken heart mesenchymal cells. This finding suggests that butyrate acts by causing non-specific inhibition of cell proliferation, rather then by specifically suppressing the neoplastic phenotype or by inducing recovery of cells from the neoplastic state. 相似文献
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Diagnosis of patients with a disorder of consciousness is very challenging. Previous studies investigating resting state networks demonstrate that 2 main features of the so-called default mode network (DMN), metabolism and functional connectivity, are impaired in patients with a disorder of consciousness. However, task-induced deactivation--a third main feature of the DMN--has not been explored in a group of patients. Deactivation of the DMN is supposed to reflect interruptions of introspective processes. Seventeen patients with unresponsive wakefulness syndrome (UWS, former vegetative state), 8 patients in minimally conscious state (MCS), and 25 healthy controls were investigated with functional magnetic resonance imaging during a passive sentence listening task. Results show that deactivation in medial regions is reduced in MCS and absent in UWS patients compared to healthy controls. Moreover, behavioral scores assessing the level of consciousness correlate with deactivation in patients. On single-subject level, all control subjects but only 2 patients in MCS and 6 with UWS exposed deactivation. Interestingly, all patients who deactivated during speech processing (except for one) showed activation in left frontal regions which are associated with conscious processing. Our results indicate that deactivation of the DMN can be associated with the level of consciousness by selecting those who are able to interrupt ongoing introspective processes. In consequence, deactivation of the DMN may function as a marker of consciousness. 相似文献
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Drug safety and efficacy are highly variable among patients. Most patients will experience the desired drug effect, but some may suffer from adverse drug reactions or gain no benefit. Pharmacogenetic testing serves as a pre-treatment diagnostic option in situations where failure or adverse events should be avoided at all costs. One such situation is human space flight. On the international space station (ISS), a list of drugs is available to cover typical emergency settings, as well as the long-term treatment of common conditions for the use in self-medicating common ailments developing over a definite period. Here, we scrutinized the list of the 78 drugs permanently available at the ISS (year 2014) to determine the extent to which their metabolism may be affected by genetic polymorphisms, potentially requiring genotype-specific dosing or choice of an alternative drug. The purpose of this analysis was to estimate the potential benefit of pharmacogenetic diagnostics in astronauts to prevent therapy failure or side effects. 相似文献
100.
Laura K. Gunther John A. Rohde Wanjian Tang Joseph A. Cirilo Jr. Christopher P. Marang Brent D. Scott David D. Thomas Edward P. Debold Christopher M. Yengo 《The Journal of biological chemistry》2020,295(51):17383
Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport. 相似文献