Long Lasting Egocentric Disorientation Induced by Normal Sensori-Motor Spatial Interaction

Perception of the cardinal directions of the body, right-left, up-down, ahead-behind, which appears so absolute and fundamental to the organisation of behaviour can in fact, be modified. Perhaps unsurprisingly, it has been shown that prolonged distorted perception of the orientation of body axes can be a consequence of disordered sensori-motor signals, including long-term prismatic adaptation and lesions of the central nervous system. We report the novel and surprising finding that a long-lasting distortion of perception of personal space can also be induced by an ecological pointing task without the artifice of distorting normal sensori-motor relationships.Twelve right-handed healthy adults performed the task of pointing with their arms, without vision, to indicate their subjective 'straight ahead', a task often used to assess the Egocentric Reference. This was performed before, immediately, and one day after a second task intended to 'modulate' perception of spatial direction. The 'modulating' task lasted 5 minutes and consisted of asking participants to point with the right finger to targets that appeared only in one (right or left) half of a computer screen. Estimates of the 'straight-ahead' during pre-test were accurate (inferior to 0.3 degrees deviation). Significantly, up to one day after performing the modulating task, the subjective 'straight-ahead' was deviated (by approximately 3.2 degrees) to the same side to which subjects had pointed to targets.These results reveal that the perception of directional axes for behaviour is readily influenced by interactions with the environment that involve no artificial distortion of normal sensori-motor-spatial relationships and does not necessarily conform to the cardinal directions as defined by the anatomy of orthostatic posture. We thus suggest that perceived space is a dynamic construction directly dependent upon our past experience about the direction and/or the localisation of our sensori-motor spatial interaction with environment

Variation in limb loading magnitude and timing in tetrapods

Comparative analyses of locomotion in tetrapods reveal two patterns of stride cycle variability. Tachymetabolic tetrapods (birds and mammals) have lower inter-cycle variation in stride duration than bradymetabolic tetrapods (amphibians, lizards, turtles, and crocodilians). This pattern has been linked to the fact that birds and mammals share enlarged cerebella, relatively enlarged and heavily myelinated Ia afferents, and γ-motoneurons to their muscle spindles. Tachymetabolic tetrapod lineages also both possess an encapsulated Golgi tendon morphology, thought to provide more spatially precise information on muscle tension. The functional consequence of this derived Golgi tendon morphology has never been tested. We hypothesized that one advantage of precise information on muscle tension would be lower and more predictable limb bone stresses, achieved in tachymetabolic tetrapods by having less variable substrate reaction forces than bradymetabolic tetrapods. To test this hypothesis, we analyzed hindlimb substrate reaction forces during locomotion of 55 tetrapod species in a phylogenetic comparative framework. Variation in species-means of limb loading magnitude and timing confirm that, for most of the variables analyzed, variance in hindlimb loading and timing is significantly lower in species with encapsulated versus unencapsulated Golgi tendon organs. These findings suggest that maintaining predictable limb loading provides a selective advantage for birds and mammals by allowing for energy-savings during locomotion, lower limb bone safety factors, and quicker recovery from perturbations. The importance of variation in other biomechanical variables in explaining these patterns, such as posture, effective mechanical advantage, and center-of-mass mechanics, remains to be clarified

Syndecan-1 Regulates Vasculat Smooth Muscle Cell Phenotype

Objective: We examined the role of syndecan-1 in modulating the phenotype of vascular smooth muscle cells in the context of endogenous inflammatory factors and altered microenvironments that occur in disease or injury-induced vascular remodeling. Methods and Results: Vascular smooth muscle cells (vSMCs) display a continuum of phenotypes that can be altered during vascular remodeling. While the syndecans have emerged as powerful and complex regulators of cell function, their role in controlling vSMC phenotype is unknown. Here, we isolated vSMCs from wild type (WT) and syndecan-1 knockout (S1KO) mice. Gene expression and western blotting studies indicated decreased levels of α-smooth muscle actin (α-SMA), calponin, and other vSMC-specific differentiation markers in S1KO relative to WT cells. The spread area of the S1KO cells was found to be greater than WT cells, with a corresponding increase in focal adhesion formation, Src phosphorylation, and alterations in actin cytoskeletal arrangement. In addition, S1KO led to increased S6RP phosphorylation and decreased AKT and PKC-α phosphorylation. To examine whether these changes were present in vivo, isolated aortae from aged WT and S1KO mice were stained for calponin. Consistent with our in-vitro findings, the WT mice aortae stained higher for calponin relative to S1KO. When exposed to the inflammatory cytokine TNF-α, WT vSMCs had an 80% reduction in syndecan-1 expression. Further, with TNF-α, S1KO vSMCs produced increased pro-inflammatory cytokines relative to WT. Finally, inhibition of interactions between syndecan-1 and integrins αvβ3 and αvβ5 using the inhibitory peptide synstatin appeared to have similar effects on vSMCs as knocking out syndecan-1, with decreased expression of vSMC differentiation markers and increased expression of inflammatory cytokines, receptors, and osteopontin. Conclusions: Taken together, our results support that syndecan-1 promotes vSMC differentiation and quiescence. Thus, the presence of syndecan-1 would have a protective effect against vSMC dedifferentiation and this activity is linked to interactions with integrins αvβ3 and αvβ5.This study was supported by the American Heart Association (10SDG2630139) and the National Institutes of Health (1DP2OD008716-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biomedical EngineeringEmail: [email protected] (SC), Email: [email protected] (AB

Western blotting for increased expression of ICAM-1 and osteopontin.

<p>*Statistically significant difference with WT group under similar culture conditions. †Statistically significant difference with non-heparin treated WT group. ‡Statistically significant differences with non-heparin treated WT/synstatin group.</p

Syndecan-1 knockout increases vSMC proliferation and induces a more spread adherent cell morphology.

<p>(A) Cell proliferation measured using an MTS assay demonstrated faster growth in syndecan-1 knockout (S1KO) vSMCs versus wild type (WT) vSMCs. (B) DNA synthesis in S1KO and WT cell lines, as indicated by the BrdU index. (C) Altered morphology of S1KO vSMCs when subjected to changes in the biochemical environment, specifically control (1% FBS), medium containing 30 µg/mL heparin, and medium containing 30 µg/mL heparin and 5 ng/mL TGF-β1. (D) Cell area after spreading was smaller for WT vSMCs in comparison to S1KO vSMCs. (E) Shape factor determinations indicated that S1KO vSMCs were more circular than WT vSMCs. (F) Elliptical form factor (EFF) determinations indicated that S1KO vSMCs were shorter and wider than their WT counterparts. Scale bar is 100 µm. *Statistically significant difference with WT group under similar culture conditions (p<0.05).</p

Measurement of protein levels of α-SMA and calponin in cultured vSMCs confirmed the upregulation of α-SMA and calponin in WT vSMCs.

<p>(A, C) Western blotting for α-SMA and calponin in WT and S1KO cells after 48 hours of the shown treatments. (B, D) Immunostaining for α-SMA and calponin demonstrated higher expression in WT vSMCs versus S1KO vSMCs. Scale bars are 100 microns in length. *Statistically significant difference with WT group under similar culture conditions (p<0.05).</p

Western blotting analysis of intracellular signaling pathways in WT and S1KO vascular smooth muscle cells (vSMCs).

<p>For all western blots, cell lysates were obtained from vSMCs that were treated with 1% FBS, heparin or with heparin and TGF-β1 for 48 hours prior to cell lysis. (A) Western blotting for phospho-S6RP and total S6RP. (B) Immunoblotting analyses for phosphorylated PKC-α and total PKC-α. (C) Western blotting indicated reduced phospho-AKT in S1KO vSMCs versus WT vSMCs in heparin and heparin/TGF-β1 treated cells. In all quantification analyses, expression levels of the target protein for S1KO vSMCs were normalized to those for WT vSMCs treated with control culture medium. *Statistically significant difference with WT group under similar culture conditions (p<0.05).</p

Treatment of vascular smooth muscle cells (vSMCs) with TNF-α alters expression of syndecan-1 (sdc-1) and the absence of syndecan-1 in syndecan-1 knockout (S1KO) increases the expression of inflammatory cytokines by vSMCs.

<p>The cells were treated with 20/mL TNF-α for 48 hours. (A) Treatment of WT mouse cells with TNF-α reduces gene expression of sdc-1. (B) Baseline expression of IL-6 was lower in S1KO vSMCs but higher after stimulation with TNF-α. (C) Higher MCP-1 gene expression in S1KO vSMCs relative to WT vSMCs after stimulation with TNF-α. *Statistically significant difference with WT cell group under similar culture conditions. †Statistically significant difference with non-TNF-α treated WT cell group. ‡Statistically significant difference with non-TNF-α treated S1KO cell group.</p

Reduced expression of calponin by aged syndecan-1 knockout (S1KO) mouse aortae relative to old wild type (WT) mice aorta.

<p>(A) Immunohistochemical staining for calponin in the descending aorta harvested from the mice. (B) Morphometric quantification of calponin staining in the arteries (n = 5). All images were taken at the same length of exposure and calponin staining relative intensities were quantified. The intensities for S1KO mouse descending aorta were normalized relative to WT. Scale bars are 100 microns in length. *Statistically significant difference with WT (p<0.05).</p