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The Neural Cell Adhesion Molecule (NCAM) plays a crucial role in development of the central nervous system regulating cell migration, differentiation and synaptogenesis. NCAM mediates cell-cell adhesion through homophilic NCAM binding, subsequently resulting in activation of the fibroblast growth factor receptor (FGFR). NCAM-mediated adhesion leads to activation of various intracellular signal transduction pathways, including the Ras-mitogen activated protein kinase (MAPK) and the phosphatidylinositol-3-kinase (PI3K)-Akt pathways. A synthetic peptide derived from the second fibronectin type III module of NCAM, the FGL peptide, binds to and induces phosphorylation of FGFR without prior homophilic NCAM binding. We here present evidence that this peptide is able to mimic NCAM heterophilic binding to the FGFR by inducing neuronal differentiation as reflected by neurite outgrowth through a direct interaction with FGFR in primary cultures of three different neuronal cell types all expressing FGFR subtype 1: dopaminergic, hippocampal and cerebellar granule neurons. Moreover, we show that the FGL peptide promotes neuronal survival upon induction of cell death in the same three cell types. The effects of the FGL peptide are shown to depend on activation of FGFR and the MAPK and PI3K intracellular signalling pathways, all three kinases being necessary for the effects of FGL on neurite outgrowth and neuronal survival. The neural cell adhesion molecule, NCAM, is a membraneassociated glycoprotein expressed on the surface of neurons and glial cells. NCAM plays a key role in morphogenesis of the nervous system, synaptic plasticity in relation to learning and memory consolidation, and regeneration of damaged neural tissue (Rønn et al. 1998).NCAM is a member of the immunoglobulin (Ig) superfamily and mediates cell)cell adhesion. It is involved in homophilic interactions (NCAM binding to NCAM) between opposing, NCAM-expressing cells and heterophilic binding between NCAM and a series of proteins including the fibroblast growth factor receptor (FGFR), the neuronal cell adhesion molecule L1 and different types of collagens and proteoglycans Crossin and Krushel 2000;Povlsen et al. 2003;Hinsby et al. 2004). Additionally, NCAM has recently been shown to bind glial cell Abbreviations used: Ab 25-35, Amyloid-b peptide; BDNF, brainderived neurotrophic factor; CGN, cerebellar granule neurons; Erk1/2, extracellular signal-regulated kinases 1 and 2; F3, fibronectin type III module; FAK, focal adhesion kinase; FGFR, fibroblast growth factor receptor; FGLd, FG loop peptide dendrimer; FGLm, FG loop peptide monomer; GDNF, glial cell line-derived neurotrophic factor; Ig, immunoglobulin; IGF-1, insulin-like growth factor 1; MAPK, Ras-mitogen activated protein kinase; NCAM, neural cell adhesion molecule; 6-OHDA, 6-hydroxydopamine; PI3K, phosphatidylinositol-3-kinase; PKC, protein kinase C; PLCc, phospholipase Cc.

This national survey is the largest series of nasal vestibule cancer ever published. Wang classification is more prognostic and easier to use than the Union Internationale Contre le Cancer 2002. Surgery or hypofractionated RT can be used for T1 lesions, whereas larger lesions should be treated with combined approach.

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In many social species, groups of animals defend a shared territory against rival conspecifics. Intruders can be detected from a variety of cues, including faecal deposits, and the strength of response is expected to vary depending on the identity of the rival group. Previous studies examining differences in response to neighbour and stranger groups have focused on the immediate response to the relevant cues. Here, we investigated how simulated intrusions of rival groups affect both immediate responses and post-inspection movement patterns. To do so, we used a faecal translocation experiment at latrine sites within the territories of dwarf mongoose Helogale parvula groups. Immediate responses were adjusted to the level of threat, with greater scentmarking behaviour, time spent at the latrine and group-member participation when groups were presented with faecal matter from out-group rivals relative to control (own-group and herbivore) faeces. Subsequent movement of the group was also affected by threat level, with a decrease in speed and distance covered following simulated intrusions by out-group rivals compared to control conditions. However, there were no significant differences in immediate responses or post-latrine movement patterns when comparing simulated neighbour and stranger intrusions. These results indicate that territorial intrusions can elicit not just an immediate change in behaviour but more farreaching consequences in terms of movement dynamics. They also raise the possibility that neighbour-stranger discrimination predictions are not necessarily as clear-cut as previously described.

In social species, conspecific outsiders present various threats to groups and their members. These out-group threats are predicted to affect subsequent within-group interactions (e.g., affiliation and aggression) and individual behavior (e.g., foraging and vigilance decisions). However, experimental investigations of such consequences are rare, especially in natural conditions. We used field-based call playbacks and fecal presentations on habituated wild dwarf mongooses (Helogale parvula)—a cooperatively breeding, territorial species—to examine postinteraction responses to the simulated threat of a rival group. Dwarf mongooses invested more in grooming of groupmates, foraged closer together, and more regularly acted as sentinels (a raised guard) after encountering indicators of rival-group presence compared to control conditions. These behavioral changes likely arise from greater anxiety and, in the case of increased vigilance, the need to seek additional information about the threat. The influence of an out-group threat lasted at least 1 h but individuals of different dominance status and sex responded similarly, potentially because all group members suffer costs if a contest with rivals is lost. Our results provide field-based experimental evidence from wild animals that out-group threats can influence within-group behavior and decision making, and suggest the need for greater consideration of the lasting impacts of social conflict.

The neural cell adhesion molecule (NCAM) can bind to and activate fibroblast growth factor receptor 1 (FGFR1). However, there are four major FGFR isoforms (FGFR1-FGFR4), and it is not known whether NCAM also interacts directly with the other three FGFR isoforms. In this study, we show by surface plasmon resonance analysis that NCAM can bind to FGFR2 with an affinity similar to that for the NCAM-FGFR1 interaction. However, the kinetic parameters for the NCAM-FGFR2 binding are different from those of the NCAM-FGFR1 binding. Both receptors were shown to cycle relatively fast between the NCAM bound and unbound states, although FGFR2 cycling was clearly faster (13 times) than the FGFR1 cycling. Moreover, ATP was more effective in inhibiting the binding of NCAM to FGFR1 than to FGFR2, indicating that the binding sites in NCAM for the two receptors are similar, but not identical.

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