Functional organization of vestibulospinal inputs on thoracic motoneurons responsible for trunk postural control in Xenopus.

KEY POINTS: Vestibulospinal reflexes participate in postural control. How this is achieved has not been investigated fully. We combined electrophysiological, neuroanatomical and imaging techniques to decipher the vestibulospinal network controlling the activation of back and limb muscles responsible for postural adjustments. We describe two distinct pathways activating either thoracic postural motoneurons alone or thoracic and lumbar motoneurons together, with the latter co-ordinating specifically hindlimb extensors and postural back muscles. ABSTRACT: In vertebrates, trunk postural stabilization is known to rely mainly on direct vestibulospinal inputs on spinal axial motoneurons. However, a substantial role of central spinal commands ascending from lumbar segments is not excluded during active locomotion. In the adult Xenopus, a lumbar drive dramatically overwhelms the descending inputs onto thoracic postural motoneurons during swimming. Given that vestibulospinal fibres also project onto the lumbar segments that shelter the locomotor generators, we investigated whether such a lumbo-thoracic pathway may relay vestibular information and consequently, also be involved in the control of posture at rest. We show that thoracic postural motoneurons exhibit particular dendritic spatial organization allowing them to gather information from both sides of the cord. In response to passive head motion, these motoneurons display both early and delayed discharges, with the latter occurring in phase with ipsilateral hindlimb extensor bursts. We demonstrate that both vestibulospinal and lumbar ascending fibres converge onto postural motoneurons, and that thoracic motoneurons monosynaptically respond to the electrical stimulation of either pathway. Finally, we show that vestibulospinal fibres project to and activate lumbar interneurons with thoracic projections. Taken together, our results complete the scheme of the vestibulospinal control of posture by illustrating the existence of a novel, indirect pathway, which implicates lumbar interneurons relaying vestibular inputs to thoracic motoneurons, and participating in global body postural stabilization in the absence of active locomotion.

Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging.

Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin.

Segmental organization of vestibulospinal inputs to spinal interneurons mediating crossed activation of thoracolumbar motoneurons in the neonatal mouse.

Vestibulospinal pathways activate contralateral motoneurons (MNs) in the thoracolumbar spinal cord of the neonatal mouse exclusively via axons descending ipsilaterally from the vestibular nuclei via the lateral vestibulospinal tract (LVST; Kasumacic et al., 2010). Here we investigate how transmission from the LVST to contralateral MNs is mediated by descending commissural interneurons (dCINs) in different spinal segments. We test the polysynaptic nature of this crossed projection by assessing LVST-mediated ventral root (VR) response latencies, manipulating synaptic responses pharmacologically, and tracing the pathway transynaptically from hindlimb extensor muscles using rabies virus (RV). Longer response latencies in contralateral than ipsilateral VRs, near-complete abolition of LVST-mediated calcium responses in contralateral MNs by mephenesin, and the absence of transsynaptic RV labeling of contralateral LVST neurons within a monosynaptic time window all indicate an overwhelmingly polysynaptic pathway from the LVST to contralateral MNs. Optical recording of synaptically mediated calcium responses identifies LVST-responsive ipsilateral dCINs that exhibit segmental differences in proportion and dorsoventral distribution. In contrast to thoracic and lower lumbar segments, in which most dCINs are LVST responsive, upper lumbar segments stand out because they contain a much smaller and more ventrally restricted subpopulation of LVST-responsive dCINs. A large proportion of these upper lumbar LVST-responsive dCINs project to contralateral L5, which contains many of the hindlimb extensor MNs activated by the LVST. A selective channeling of LVST inputs through segmentally and dorsoventrally restricted subsets of dCINs provides a mechanism for targeting vestibulospinal signals differentially to contralateral trunk and hindlimb MNs in the mammalian spinal cord.

Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni.

An organometallic derivative of praziquantel was studied directly in worms by using inductively coupled plasma-mass spectrometry (ICP-MS) for quantification and synchrotron-based imaging. X-ray fluorescence (XRF) and IR absorption spectromicroscopy were used for the first time in combination to directly locate this organometallic drug candidate in schistosomes. The detection of both CO (IR) and Cr (XRF) signatures proved that the Cr(CO)3 core remained intact in the worms. Images showed a preferential accumulation at the worm's tegument, consistent with a possible targeting of the calcium channel but not excluding other biological targets inside the worm.

Adaptive plasticity of spino-extraocular motor coupling during locomotion in metamorphosing Xenopus laevis.

During swimming in the amphibian ITALIC! Xenopus laevis, efference copies of rhythmic locomotor commands produced by the spinal central pattern generator (CPG) can drive extraocular motor output appropriate for producing image-stabilizing eye movements to offset the disruptive effects of self-motion. During metamorphosis, ITALIC! X. laevisremodels its locomotor strategy from larval tail-based undulatory movements to bilaterally synchronous hindlimb kicking in the adult. This change in propulsive mode results in head/body motion with entirely different dynamics, necessitating a concomitant switch in compensatory ocular movements from conjugate left-right rotations to non-conjugate convergence during the linear forward acceleration produced during each kick cycle. Here, using semi-intact or isolated brainstem/spinal cord preparations at intermediate metamorphic stages, we monitored bilateral eye motion along with extraocular, spinal axial and limb motor nerve activity during episodes of spontaneous fictive swimming. Our results show a progressive transition in spinal efference copy control of extraocular motor output that remains adapted to offsetting visual disturbances during the combinatorial expression of bimodal propulsion when functional larval and adult locomotor systems co-exist within the same animal. In stages at metamorphic climax, spino-extraocular motor coupling, which previously derived from axial locomotor circuitry alone, can originate from both axial and ITALIC! de novohindlimb CPGs, although the latter's influence becomes progressively more dominant and eventually exclusive as metamorphosis terminates with tail resorption. Thus, adaptive interactions between locomotor and extraocular motor circuitry allows CPG-driven efference copy signaling to continuously match the changing spatio-temporal requirements for visual image stabilization throughout the transitional period when one propulsive mechanism emerges and replaces another.

Entasis through hook-and-loop fastening in a glycoligand with cumulative weak forces stabilizing Cu(I).

The idea of a possible control of metal ion properties by constraining the coordination sphere geometry was introduced by Vallee and Williams with the concept of entasis, which is frequently postulated to be at stake in metallobiomolecules. However, the interactions controlling the geometry at metal centers remain often elusive. In this study, the coordination properties toward copper ions­Cu(II) or Cu(I)­of a geometrically constrained glycoligand centered on a sugar scaffold were compared with those of an analogous ligand built on an unconstrained alkyl chain. The sugar-centered ligand was shown to be more preorganized for Cu(II) coordination than its open-chain analogue, with an unusual additional stabilization of the Cu(I) redox state. This preference for Cu(I) was suggested to arise from geometric constraints favoring an optimized folding of the glycoligand minimizing steric repulsions. In other words, the Cu(I) d(10) species is stabilized by valence shell electron pair repulsion (VSEPR). This idea was rationalized by a theoretical noncovalent interactions (NCI) analysis. The cumulative effects of weak forces were shown to create an efficient buckle as in a hook-and-loop fastener, and fine structural features within the glycoligand reduce repulsive interactions for the Cu(I) state. This study emphasizes that monosaccharide platforms are appropriate ligand backbones for a delicate geometric control at the metal center, with a network of weak interactions within the ligand. This structuration availing in glycoligands makes them attractive for metallic entasis.

Restricted neural plasticity in vestibulospinal pathways after unilateral labyrinthectomy as the origin for scoliotic deformations.

Adolescent idiopathic scoliosis in humans is often associated with vestibulomotor deficits. Compatible with a vestibular origin, scoliotic deformations were provoked in adult Xenopus frogs by unilateral labyrinthectomy (UL) at larval stages. The aquatic ecophysiology and absence of body-weight-supporting limb proprioceptive signals in amphibian tadpoles as a potential sensory substitute after UL might be the cause for a persistent asymmetric descending vestibulospinal activity. Therefore, peripheral vestibular lesions in larval Xenopus were used to reveal the morphophysiological alterations at the cellular and network levels. As a result, spinal motor nerves that were modulated by the previously intact side before UL remained permanently silent during natural vestibular stimulation after the lesion. In addition, retrograde tracing of descending pathways revealed a loss of vestibular neurons on the ipsilesional side with crossed vestibulospinal projections. This loss facilitated a general mass imbalance in descending premotor activity and a permanent asymmetric motor drive to the axial musculature. Therefore, we propose that the persistent asymmetric contraction of trunk muscles exerts a constant, uncompensated differential mechanical pull on bilateral skeletal elements that enforces a distortion of the soft cartilaginous skeletal elements and bone shapes. This ultimately provokes severe scoliotic deformations during ontogenetic development similar to the human syndrome.

Influence of the side-chain length on the cellular uptake and the cytotoxicity of rhenium triscarbonyl derivatives: a bimodal infrared and luminescence quantitative study.

Rhenium triscarbonyl complexes fac-[Re(CO)3 (N^N)] with appropriate ancillary N^N ligands are relevant for fluorescent bio-imaging. Recently, we have shown that [Re(CO)3 ] cores can also be efficiently mapped inside cells using their IR signature and that they can thus be used in a bimodal approach. To describe them we have coined the term SCoMPIs for single-core multimodal probes for imaging. In the context of the use of these SCoMPIs in bio-imaging, the questions of their cellular uptake and cytotoxicity are critical. We report here a series of compounds derived from the [Re(CO)3 Cl(pyta)] core (pyta=4-(2-pyridyl)-1,2,3-triazole). The pyta ligand is of interest because it can be easily functionalized. Aliphatic side chains (C4 , C8 , and C12 ) were appended to this core. A correlative study involving IR and luminescence was performed to monitor and quantify their cellular internalization. We studied the relationship between lipophilicity (log P(o/w)), cytotoxicity (IC50 ), and cellular uptake, and we showed that both uptake and cytotoxicity increase with the length of the side chain, with a higher uptake for the C12 derivative. This study stresses the distinction that has to be made between apparent toxicity, determined as an incubation concentration IC50 , and intrinsic toxicity. Indeed, the intrinsic toxicity of a compound can remain hidden if it is not cell permeable. Therefore it must be kept in mind that IC50 values are composite values, reflecting both cellular uptake and intrinsic toxicity.

Luminescence modulations of rhenium tricarbonyl complexes induced by structural variations.

Octahedral d(6) low-spin Re(I) tricarbonyl complexes are of considerable interest as noninvasive imaging probes and have been deeply studied owing to their biological stability, low toxicity, large Stokes shifts, and long luminescence lifetimes. We reported recently the bimodal IR and luminescence imaging of a Re(I) tricarbonyl complex with a Pyta ligand (4-(2-pyridyl)-1,2,3-triazole) in cells and labeled such metal-carbonyl complexes SCoMPIs for single-core multimodal probes for imaging. Re(I) tricarbonyl complexes have unique photophysical properties allowing for their unequivocal detection in cells but also present some weaknesses such as a very low luminescence quantum yield in aqueous medium. Further optimizations would thus be desirable. We therefore developed new Re(I) tricarbonyl complexes prepared from different ancillary ligands. Complexes with benzothiadiazole-triazole ligands show interesting luminescent quantum yields in acetonitrile and may constitute valuable luminescent metal complexes in organic media. A series of complexes with bidentate 1-(2-quinolinyl)-1,2,3-triazole (Taquin) and 1-(2-pyridyl)-1,2,3-triazole (Tapy) ligands bearing various 4-substituted alkyl side chains has been designed and synthesized with efficient procedures. Their photophysical properties have been characterized in acetonitrile and in a H2O/DMSO (98/2) mixture and compared with those of the parent Quinta- and Pyta-based complexes. Tapy complexes bearing long alkyl chains show impressive enhancement of their luminescent properties relative to the parent Pyta complex. Theoretical calculations have been performed to further characterize this new class of rhenium tricarbonyl complexes. Preliminary cellular imaging studies in MDA-MB231 breast cancer cells reveal a strong increase in the luminescence signal in cells incubated with the Tapy complex substituted with a C12 alkyl chain. This study points out the interesting potential of the Tapy ligand in coordination chemistry, which has been so far underexploited.

Toward optimal spatial and spectral quality in widefield infrared spectromicroscopy of IR labelled single cells.

Advancements in widefield infrared spectromicroscopy have recently been demonstrated following the commissioning of IRENI (InfraRed ENvironmental Imaging), a Fourier Transform infrared (FTIR) chemical imaging beamline at the Synchrotron Radiation Center. The present study demonstrates the effects of magnification, spatial oversampling, spectral pre-processing and deconvolution, focusing on the intracellular detection and distribution of an exogenous metal tris-carbonyl derivative 1 in a single MDA-MB-231 breast cancer cell. We demonstrate here that spatial oversampling for synchrotron-based infrared imaging is critical to obtain accurate diffraction-limited images at all wavelengths simultaneously. Resolution criteria and results from raw and deconvoluted images for two Schwarzschild objectives (36×, NA 0.5 and 74×, NA 0.65) are compared to each other and to prior reports for raster-scanned, confocal microscopes. The resolution of the imaging data can be improved by deconvolving the instrumental broadening that is determined with the measured PSFs, which is implemented with GPU programming architecture for fast hyperspectral processing. High definition, rapidly acquired, FTIR chemical images of respective spectral signatures of the cell 1 and shows that 1 is localized next to the phosphate- and Amide-rich regions, in agreement with previous infrared and luminescence studies. The infrared image contrast, localization and definition are improved after applying proven spectral pre-processing (principal component analysis based noise reduction and RMie scattering correction algorithms) to individual pixel spectra in the hyperspectral cube.

Detection of an estrogen derivative in two breast cancer cell lines using a single core multimodal probe for imaging (SCoMPI) imaged by a panel of luminescent and vibrational techniques.

3-Methoxy-17α-ethynylestradiol or mestranol is a prodrug for ethynylestradiol and the estrogen component of some oral contraceptive formulations. We demonstrate here that a single core multimodal probe for imaging - SCoMPI - can be efficiently grafted onto mestranol allowing its tracking in two breast cancer cell lines, MDA-MB-231 and MCF-7 fixed cells. Correlative imaging studies based on luminescence (synchrotron UV spectromicroscopy, wide field and confocal fluorescence microscopies) and vibrational (AFMIR, synchrotron FTIR spectromicroscopy, synchrotron-based multiple beam FTIR imaging, confocal Raman microspectroscopy) spectroscopies were consistent with one another and showed a Golgi apparatus distribution of the SCoMPI-mestranol conjugate in both cell lines.

Locomotor efference copy signaling and gaze control: An evolutionary perspective.

Neural replicas of the spinal motor commands that drive locomotion have become increasingly recognized as an intrinsic neural mechanism for producing gaze-stabilizing eye movements that counteract the perturbing effects of self-generated head/body motion. By pre-empting reactive signaling by motion-detecting vestibular sensors, such locomotor efference copies (ECs) provide estimates of the sensory consequences of behavioral action. Initially demonstrated in amphibian larvae during spontaneous fictive swimming in deafferented in vitro preparations, direct evidence for a contribution of locomotor ECs to gaze stabilization now extends to the ancestral lamprey and to tetrapod adult frogs and mice. Supporting behavioral evidence also exists for other mammals, including humans, therefore further indicating the mechanism's conservation during vertebrate evolution. The relationship between feedforward ECs and vestibular sensory feedback in ocular movement control is variable, ranging from additive to the former supplanting the latter, depending on vestibular sensing ability, and the intensity and regularity of rhythmic locomotor movements.

Role of locomotor efference copy in vertebrate gaze stabilization.

Vertebrate locomotion presents a major challenge for maintaining visual acuity due to head movements resulting from the intimate biomechanical coupling with the propulsive musculoskeletal system. Retinal image stabilization has been traditionally ascribed to the transformation of motion-related sensory feedback into counteracting ocular motor commands. However, extensive exploration of spontaneously active semi-intact and isolated brain/spinal cord preparations of the amphibian Xenopus laevis, have revealed that efference copies (ECs) of the spinal motor program that generates axial- or limb-based propulsion directly drive compensatory eye movements. During fictive locomotion in larvae, ascending ECs from rostral spinal central pattern generating (CPG) circuitry are relayed through a defined ascending pathway to the mid- and hindbrain ocular motor nuclei to produce conjugate eye rotations during tail-based undulatory swimming in the intact animal. In post-metamorphic adult frogs, this spinal rhythmic command switches to a bilaterally-synchronous burst pattern that is appropriate for generating convergent eye movements required for maintaining image stability during limb kick-based rectilinear forward propulsion. The transition between these two fundamentally different coupling patterns is underpinned by the emergence of altered trajectories in spino-ocular motor coupling pathways that occur gradually during metamorphosis, providing a goal-specific, morpho-functional plasticity that ensures retinal image stability irrespective of locomotor mode. Although the functional impact of predictive ECs produced by the locomotory CPG matches the spatio-temporal specificity of reactive sensory-motor responses, rather than contributing additively to image stabilization, horizontal vestibulo-ocular reflexes (VORs) are selectively suppressed during intense locomotor CPG activity. This is achieved at least in part by an EC-mediated attenuation of mechano-electrical encoding at the vestibular sensory periphery. Thus, locomotor ECs and their potential suppressive impact on vestibular sensory-motor processing, both of which have now been reported in other vertebrates including humans, appear to play an important role in the maintenance of stable vision during active body displacements.

Locomotion-induced ocular motor behavior in larval Xenopus is developmentally tuned by visuo-vestibular reflexes.

Locomotion in vertebrates is accompanied by retinal image-stabilizing eye movements that derive from sensory-motor transformations and predictive locomotor efference copies. During development, concurrent maturation of locomotor and ocular motor proficiency depends on the structural and neuronal capacity of the motion detection systems, the propulsive elements and the computational capability for signal integration. In developing Xenopus larvae, we demonstrate an interactive plasticity of predictive locomotor efference copies and multi-sensory motion signals to constantly elicit dynamically adequate eye movements during swimming. During ontogeny, the neuronal integration of vestibulo- and spino-ocular reflex components progressively alters as locomotion parameters change. In young larvae, spino-ocular motor coupling attenuates concurrent angular vestibulo-ocular reflexes, while older larvae express eye movements that derive from a combination of the two components. This integrative switch depends on the locomotor pattern generator frequency, represents a stage-independent gating mechanism, and appears during ontogeny when the swim frequency naturally declines with larval age.

Perinatal development of central vestibular neurons in mice.

Central circuitry of the vestibular nuclei integrates sensory inputs in the adaptive control of motor behaviors such as posture, locomotion, and gaze stabilization. Thus far, such circuits have been mostly examined at mature stages, whereas their emergence and early development have remained poorly described. Here, we focused on the perinatal period of murine development, from embryonic day E14.5 to post-natal day P5, to investigate the ontogeny of two functionally distinct vestibular neuronal groups, neurons projecting to the spinal cord via the lateral vestibulospinal tract (LVST) and commissural neurons of the medial vestibular nucleus that cross the midline to the contralateral nucleus. Using transgenic mice and retrograde labeling, we found that network-constitutive GABAergic and glycinergic neurons are already established in the two vestibular groups at embryonic stages. Although incapable of repetitive firing at E14.5, neurons of both groups can generate spike trains from E15.5 onward and diverge into previously established A or B subtypes according to the absence (A) or presence (B) of a two-stage spike after hyperpolarization. Investigation of several voltage-dependent membrane properties indicated that solely LVST neurons undergo significant maturational changes in their electrophysiological characteristics during perinatal development. The proportions of A vs B subtypes also evolve in both groups, with type A neurons remaining predominant at all stages, and type B commissural neurons appearing only post-natally. Together, our results indicate that vestibular neurons acquire their distinct morpho-functional identities after E14.5 and that the early maturation of membrane properties does not emerge uniformly in the different functional subpopulations of vestibulo-motor pathways.

Conservation of locomotion-induced oculomotor activity through evolution in mammals.

Efference copies are neural replicas of motor outputs used to anticipate the sensory consequences of a self-generated motor action or to coordinate neural networks involved in distinct motor behaviors.1 An established example of this motor-to-motor coupling is the efference copy of the propulsive motor command, which supplements classical visuo-vestibular reflexes to ensure gaze stabilization during amphibian larval locomotion.2 Such feedforward replica of spinal pattern-generating circuits produces a spino-extraocular motor coupled activity that evokes eye movements, spatiotemporally coordinated to tail undulation independently of any sensory signal.3,4 Exploiting the developmental stages of the frog,1 studies in metamorphing Xenopus demonstrated the persistence of this spino-extraocular motor command in adults and its developmental adaptation to tetrapodal locomotion.5,6 Here, we demonstrate for the first time the existence of a comparable locomotor-to-ocular motor coupling in the mouse. In neonates, ex vivo nerve recordings of brainstem-spinal cord preparations reveal a spino-extraocular motor coupled activity similar to the one described in Xenopus. In adult mice, trans-synaptic rabies virus injections in lateral rectus eye muscle label cervical spinal cord neurons closely connected to abducens motor neurons. Finally, treadmill-elicited locomotion in decerebrated preparations7 evokes rhythmic eye movements in synchrony with the limb gait pattern. Overall, our data are evidence for the conservation of locomotor-induced eye movements in vertebrate lineages. Thus, in mammals as in amphibians, CPG-efference copy feedforward signals might interact with sensory feedback to ensure efficient gaze control during locomotion.

Intrinsically fluorescent glycoligands to study metal selectivity.

Glycoligands are a versatile family of ligands centered on a sugar platform and functionalized by Lewis bases. In this article, pentofuranoses were appended with the fluoroionophores 4-(pyridin-2'-yl)-1,2,3-triazol-1-yl and 4-(2',1',3'-benzothiadiazol-4'-yl)-1,2,3-triazol-1-yl using the "click-like" cycloaddition [2 + 3] of Huisgen catalyzed by copper(I). Their fluorescence properties were used to study metal cation complexation. A possible selective functionalization of furanoscaffolds allows the synthesis of "mixed" glycoligands with the successive insertion of these different fluoroionophores. The metal selectivity and the chelating behavior of these six resulting intrinsically fluorescent glycoligands were investigated. The change in the configuration at the carbon C3 of furanose did not influence either the metal selectivity or the binding constants. However, different selectivities and binding constants were found to depend on the nature of the fluoroionophore moieties. Overall, the triazolylbenzothiadiazolyl chelating group was shown to be less efficient than the triazolylpyridyl claw for complexation. Interestingly enough, the triazolylbenzothiadiazolyl claw, which fluoresces in the visible range, did not interfere in the binding and selectivity of the more efficient triazolylpyridyl claw. This study suggests that the triazolylbenzothiadiazolyl moiety could be used as an adequate fluorescent reporter to qualitatively monitor complexation of other moieties.

Chemical tuning of spin clock transitions in molecular monomers based on nuclear spin-free Ni(ii).

We report the existence of a sizeable quantum tunnelling splitting between the two lowest electronic spin levels of mononuclear Ni complexes. The level anti-crossing, or magnetic "clock transition", associated with this gap has been directly monitored by heat capacity experiments. The comparison of these results with those obtained for a Co derivative, for which tunnelling is forbidden by symmetry, shows that the clock transition leads to an effective suppression of intermolecular spin-spin interactions. In addition, we show that the quantum tunnelling splitting admits a chemical tuning via the modification of the ligand shell that determines the crystal field and the magnetic anisotropy. These properties are crucial to realize model spin qubits that combine the necessary resilience against decoherence, a proper interfacing with other qubits and with the control circuitry and the ability to initialize them by cooling.

Vestibular asymmetry as the cause of idiopathic scoliosis: a possible answer from Xenopus.

Human idiopathic scoliosis is characterized by severe deformations of the spine and skeleton. The occurrence of vestibular-related deficits in these patients is well established but it is unclear whether a vestibular pathology is the common cause for the scoliotic syndrome and the gaze/posture deficits or if the latter behavioral deficits are a consequence of the scoliotic deformations. A possible vestibular origin was tested in the frog Xenopus laevis by unilateral removal of the labyrinthine endorgans at larval stages. After metamorphosis into young adult frogs, X-ray images and three-dimensional reconstructed micro-computer tomographic scans of the skeleton showed deformations similar to those of scoliotic patients. The skeletal distortions consisted of a curvature of the spine in the frontal and sagittal plane, a transverse rotation along the body axis and substantial deformations of all vertebrae. In terrestrial vertebrates, the initial postural syndrome after unilateral labyrinthectomy recovers over time and requires body weight-supporting limb proprioceptive information. In an aquatic environment, however, this information is absent. Hence, the lesion-induced asymmetric activity in descending spinal pathways and the resulting asymmetric muscular tonus persists. As a consequence the mostly cartilaginous skeleton of the frog tadpoles progressively deforms. Lack of limb proprioceptive signals in an aquatic environment is thus the element, which links the Xenopus model with human scoliosis because a comparable situation occurs during gestation in utero. A permanently imbalanced activity in descending locomotor/posture control pathways might be the common origin for the observed structural and behavioral deficits in humans as in the different animal models of scoliosis.

Sugars to control ligand shape in metal complexes: conformationally constrained glycoligands with a predetermination of stereochemistry and a structural control.

In coordination chemistry, ligand shape can be used to tune properties, such as metal selectivity, coordination number, electronic structure, redox potential, and metal center stereochemistry including coordination helicates formation, and also to generate cavities for encapsulation. The results presented in this article indicate that two epimeric glycoligands (3 and 4) based on the conformationally restrained xylo- and ribo-1,2-O-isopropylidenefurano scaffolds are preorganized in water through pi-pi stacking due to hydrophobic interactions, as evidenced from excimer observation. The structure obtained in the solid state for one of the Cu(II) complexes (5) is chiral, with an original helical chirality arising from the coiling of the two ligands around the Cu-Cu axis. It shows an unusual double-deck type structure, with pi-pi interaction between two triazoyl-pyridyl rings and with a small cavity between the two Cu(II) ions able to host a bridging water molecule, as suggested by electron paramagnetic resonance. The Cu(II) complex from the epimeric ligand (6) shows similar properties with a mirror-image CD spectrum in the d-d region of the Cu(II). There is a predetermination of chirality at the metal center by the glycoligand induced by the C3 configuration, 6 and 5 being pseudoenantiomers. Interestingly, the stereochemistry at the metal center is here controlled by the combination of pi-stacking and chiral backbone.