Nuclear factor of activated T cells (NFAT) was first identified more than two decades ago as a major stimulation-responsive DNA-binding factor and transcriptional regulator in T cells. It is now clear that NFAT proteins have important functions in other cells of the immune system and regulate numerous developmental programmes in vertebrates. Dysregulation of these programmes can lead to malignant growth and cancer. This Review focuses on recent advances in our understanding of the transcriptional functions of NFAT proteins in the immune system and provides new insights into their potential roles in cancer development.
Sustainable supply chain management has emerged as a growing topic, receiving increasing interest in the sustainability and supply chain management area. So far, the fi eld is dominated by either case or survey based research. Few attempts have been made to take a broader look at the overarching issues, which form core topics of sustainable supply chain management. This paper presents the fi ndings from a Delphi study where experts were asked to contribute their opinion. The Delphi study allows an aggregation of these opinions and extracts underlying topics in a structured manner. Four major topics were identifi ed, which are (1) pressures and incentives for sustainable supply chain management, (2) identifying and measuring impacts on sustainable supply chain management, (3) supplier management (particularly addressing issues at the supplier-buyer interface) and (4) supply chain management (dealing with issues across all companies involved in the supply chain). The research presented contributes to substantiating and consolidating the fi eld of sustainable supply chain management.
Rab3 interacting molecules (RIMs) are evolutionarily conserved scaffolding proteins that are located at presynaptic active zones. In the mammalian nervous system, RIMs have two major activities that contribute to the fidelity of baseline synaptic transmission: they concentrate calcium channels at the active zone and facilitate synaptic vesicle docking/priming. Here we confirm that RIM has an evolutionarily conserved function at the Drosophila neuromuscular junction and then define a novel role for RIM during homeostatic synaptic plasticity. We show that loss of RIM disrupts baseline vesicle release, diminishes presynaptic calcium influx, and diminishes the size of the readily-releasable pool (RRP) of synaptic vesicles, consistent with known activities of RIM. However, loss of RIM also completely blocks the homeostatic enhancement of presynaptic neurotransmitter release that normally occurs after inhibition of postsynaptic glutamate receptors, a process termed synaptic homeostasis. It is established that synaptic homeostasis requires enhanced presynaptic calcium influx as a mechanism to potentiate vesicle release. However, despite a defect in baseline calcium influx in rim mutants, the homeostatic modulation of calcium influx proceeds normally. Synaptic homeostasis is also correlated with an increase in the size of the RRP of synaptic vesicles, although the mechanism remains unknown. Here we demonstrate that the homeostatic modulation of the RRP is blocked in the rim mutant background. Therefore, RIM-dependent modulation of the RRP is a required step during homeostatic plasticity. By extension, homeostatic plasticity appears to require two genetically separable processes, the enhancement of presynaptic calcium influx and a RIM-dependent modulation of the RRP.
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