Challenges for identifying the neural mechanisms that support spatial navigation: the impact of spatial scale.

Spatial navigation is a fascinating behavior that is essential for our everyday lives. It involves nearly all sensory systems, it requires numerous parallel computations, and it engages multiple memory systems. One of the key problems in this field pertains to the question of reference frames: spatial information such as direction or distance can be coded egocentrically-relative to an observer-or allocentrically-in a reference frame independent of the observer. While many studies have associated striatal and parietal circuits with egocentric coding and entorhinal/hippocampal circuits with allocentric coding, this strict dissociation is not in line with a growing body of experimental data. In this review, we discuss some of the problems that can arise when studying the neural mechanisms that are presumed to support different spatial reference frames. We argue that the scale of space in which a navigation task takes place plays a crucial role in determining the processes that are being recruited. This has important implications, particularly for the inferences that can be made from animal studies in small scale space about the neural mechanisms supporting human spatial navigation in large (environmental) spaces. Furthermore, we argue that many of the commonly used tasks to study spatial navigation and the underlying neuronal mechanisms involve different types of reference frames, which can complicate the interpretation of neurophysiological data

1,1'-Binaphthyl-2,2'-diamine-Based Chiral Phosphorous Triamides: Synthesis and Application in Asymmetric Catalysis

A set of chiral monodentate phosphorous triamides (PTA) comprising 1,1'-binaphthyl-2,2'-diamine as the common moiety have been synthesised. Electronic and steric tuning of the ligands was achieved by variation of the substituents at the diamine nitrogen atoms by incorporating methyl, p-tolyl and tosyl groups. Both chiral and achiral building blocks were used as monoamine components. Notably, (11bR)-3,5-dimethyl-N,N-bis[(S)-1-phenylethyl]-3,5-dihydro-4H-dinaphtho[2,1-d:1',2'-f][1,3,2]diazaphosphepin-4-amine, which is the PTA most closely related to the Feringa phosphoramidite ligand, was synthesised and characterised by NMR spectroscopy and X-ray diffraction. This PTA displays increased conformational rigidity in comparison with the corresponding phosphoramidite and adopts a C1-symmetric structure both in the solid state and in solution, even at room temperature. The new PTA ligands were used in the copper-catalysed conjugate addition of diethylzinc to cyclohex-2-enone and the nickel-catalysed hydrovinylation of styrene giving good activities and chemoselectivities at moderate enantioselectivities in both reactions.

Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons from gene expression analysis

International audienceThe formation of granulomas is associated with the resolution of Q fever, a zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells (PBMCs) and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells of which more than 50% were commonly modulated genes in response to C. burnetii and BCG. They included M1-related genes and genes related to chemotaxis. The inhibition of the chemokines, CCL2 and CCL5, directly interfered with granuloma formation. C. burnetii granulomas also expressed a specific transcriptional profile that was essentially enriched in genes associated with type I interferon response. Our results showed that granuloma formation is associated with a core of transcriptional response based on inflammatory genes. The specific granulomatous response to C. burnetii is characterized by the activation of type 1 interferon pathway