Time-mapping and future-oriented behavior in free-ranging wild fruit bats.

Episodic memory and mental time travel have been viewed as uniquely human traits.1,2,3 This view began to shift with the development of behavioral criteria to assess what is referred to as "episodic-like memory" in animals.4,5 Key findings have ranged from evidence of what-where-when memory in scrub-jays, rats, and bees; through decision-making that impacts future foraging in frugivorous primates; to evidence of planning based on future needs in scrub-jays and tool use planning in great apes.4,6,7,8,9,10,11,12,13 Field studies of these issues have been rare, though there is field-based evidence for future-oriented behaviors in primates.8,10,14,15 We report evidence that free-ranging wild fruit bats rely on mental temporal maps and exhibit future-oriented behaviors when foraging. We tracked young bats as they navigated and foraged, documenting every tree they visited over many months. We prevented the bats from foraging outside for different time periods and monitored their foraging decisions, revealing that the bats map the spatiotemporal patterns of resources in their environment. Following a long period in captivity, the bats did not visit those trees that were no longer providing fruit. We show that this time-mapping ability requires experience and is lacking in inexperienced bats. Careful analysis of the bats' movement and foraging choices indicated that they plan which tree to visit while still in the colony, thus exhibiting future-oriented behavior and delayed gratification on a nightly basis. Our findings demonstrate how the need for spatiotemporal mental mapping can drive the evolution of high cognitive abilities that were previously considered exclusive to humans.

A ceramide-1-phosphate analogue, PCERA-1, simultaneously suppresses tumour necrosis factor-alpha and induces interleukin-10 production in activated macrophages.

Tight regulation of the production of the key pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) is essential for the prevention of chronic inflammatory diseases. In vivo administration of a synthetic phospholipid, named hereafter phospho-ceramide analogue-1 (PCERA-1), was previously found to suppress lipopolysaccharide (LPS)-induced TNF-alpha blood levels. We therefore investigated the in vitro anti-inflammatory effects of PCERA-1. Here, we show that extracellular PCERA-1 potently suppresses production of the pro-inflammatory cytokine TNF-alpha in RAW264.7 macrophages, and in addition, independently and reciprocally regulates the production of the anti-inflammatory cytokine interleukin-10 (IL-10). Specificity is demonstrated by the inability of the phospholipids ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) to perform these activities. Similar TNF-alpha suppression and IL-10 induction by PCERA-1 were observed in macrophages when activated by Toll-like receptor 4 (TLR4), TLR2 and TLR7 agonists. Regulation of cytokine production is demonstrated at the mRNA and protein levels. Finally, we show that, while PCERA-1 does not block activation of nuclear factor (NF)-kappaB and mitogen-activated protein kinases by LPS, it elevates the intracellular cAMP level. In conclusion, the anti-inflammatory activity of PCERA-1 seems to be mediated by a cell membrane receptor, upstream of cAMP production, and eventually TNF-alpha suppression and IL-10 induction. Thus, identification of the PCERA-1 receptor may provide new pharmacological means to block inflammation.

Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1).

Ceramide-1-phosphate (C1P) is known as a second messenger regulating a multitude of processes including cell growth, apoptosis and inflammation. Exciting recent findings now suggest that C1P can stimulate macrophages migration in an extra-cellular manner via a G protein-coupled receptor (GPCR). Interestingly, a synthetic C1P analog, named phospho-ceramide analogue-1 (PCERA-1), was recently described as a potent in-vivo anti-inflammatory agent, and was suggested to act on macrophages in an extra-cellular manner via a GPCR. Here we summarize and compare the receptor-mediated as well as receptor-independent activities of natural C1P and its synthetic analog. We also provide experimental data in support of distinct C1P and PCERA-1 receptors.