Technology supported collaborative learning.

"This research is supported by le ministère de l'Éducation, du Loisir et du Sport dans le cadre du Programme d'aide à la recherche sur l'enseignement et l'apprentissage (PAREA)"Titre de la couv.: Technology supported collaborative learning.Titre de l'écran-titre (visionné le 10 sept. 2009).Également disponible en format papier.Bibliogr

Warped Radion Inflation

We show that the radion in a warped geometry bounded by two branes can have a potential suitable for inflation. Our construction is based upon a solution known in string theory as the linear dilaton, in which the back-reaction from a bulk scalar \Phi is exactly accounted for. The radion, stabilized by \Phi, is much heavier than the TeV scale and its couplings to the standard model are much more suppressed than in the usual Randall-Sundrum solution. We present a new formalism for obtaining approximate time-dependent solutions, based on perturbing the exact solution to the coupled Einstein and scalar field equations in the bulk. It allows the radion potential to be computed directly in terms of the brane potentials for \Phi. We show that simple exponential potentials on the branes can lead to a 4D radion potential with a flattened hilltop form, yielding inflation with a spectral index of typically n_s=0.96 and no higher than 0.99. With more complicated brane potentials, the descent from the hilltop can be a linear potential, giving a tensor-to-scalar ratio as large as r=0.07 with n_s=0.974. The couplings of the radion to the standard model particles are dictated by general covariance, so the details of reheating are explicitly calculable, leading to a reheat temperature of at least 10^7 GeV. The quantum corrections to the inflaton potential from its couplings to matter are also calculable and are shown to be small, so that the prediction for the shape of the potential is under theoretical control, even with superPlanckian field excursions.Comment: 32 pages, 15 figure

Early Evolution of Ionotropic GABA Receptors and Selective Regimes Acting on the Mammalian-Specific Theta and Epsilon Subunits

BACKGROUND: The amino acid neurotransmitter GABA is abundant in the central nervous system (CNS) of both invertebrates and vertebrates. Receptors of this neurotransmitter play a key role in important processes such as learning and memory. Yet, little is known about the mode and tempo of evolution of the receptors of this neurotransmitter. Here, we investigate the phylogenetic relationships of GABA receptor subunits across the chordates and detail their mode of evolution among mammals. PRINCIPAL FINDINGS: Our analyses support two major monophyletic clades: one clade containing GABA(A) receptor alpha, gamma, and epsilon subunits, and another one containing GABA(A) receptor rho, beta, delta, theta, and pi subunits. The presence of GABA receptor subunits from each of the major clades in the Ciona intestinalis genome suggests that these ancestral duplication events occurred before the divergence of urochordates. However, while gene divergence proceeded at similar rates on most receptor subunits, we show that the mammalian-specific subunits theta and epsilon experienced an episode of positive selection and of relaxed constraints, respectively, after the duplication event. Sites putatively under positive selection are placed on a three-dimensional model obtained by homology-modeling. CONCLUSIONS: Our results suggest an early divergence of the GABA receptor subunits, before the split from urochordates. We show that functional changes occurred in the lineages leading to the mammalian-specific subunit theta, and we identify the amino acid sites putatively responsible for the functional divergence. We discuss potential consequences for the evolution of mammals and of their CNS

Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets

Type 1 diabetes is characterized by destruction of insulin-producing β cells in the pancreatic islets by effector T cells. Tregs, defined by the markers CD4 and FoxP3, regulate immune responses by suppressing effector T cells and are recruited to sites of action by the chemokine CCL22. Here, we demonstrate that production of CCL22 in islets after intrapancreatic duct injection of double-stranded adeno-associated virus encoding CCL22 recruits endogenous Tregs to the islets and confers long-term protection from autoimmune diabetes in NOD mice. In addition, adenoviral expression of CCL22 in syngeneic islet transplants in diabetic NOD recipients prevented β cell destruction by autoreactive T cells and thereby delayed recurrence of diabetes. CCL22 expression increased the frequency of Tregs, produced higher levels of TGF-β in the CD4+ T cell population near islets, and decreased the frequency of circulating autoreactive CD8+ T cells and CD8+ IFN-γ–producing T cells. The protective effect of CCL22 was abrogated by depletion of Tregs with a CD25-specific antibody. Our results indicate that islet expression of CCL22 recruits Tregs and attenuates autoimmune destruction of β cells. CCL22-mediated recruitment of Tregs to islets may be a novel therapeutic strategy for type 1 diabetes

Response scale selection in adult pain measures: results from a literature review

Abstract Background The purpose of this literature review was to examine the existing patient-reported outcome measurement literature to understand the empirical evidence supporting response scale selection in pain measurement for the adult population. Methods The search strategy involved a comprehensive, structured, literature review with multiple search objectives and search terms. Results The searched yielded 6918 abstracts which were reviewed against study criteria for eligibility across the adult pain objective. The review included 42 review articles, consensus guidelines, expert opinion pieces, and primary research articles providing insights into optimal response scale selection for pain assessment in the adult population. Based on the extensive and varied literature on pain assessments, the adult pain studies typically use simple response scales with single-item measures of pain—a numeric rating scale, visual analog scale, or verbal rating scale. Across 42 review articles, consensus guidelines, expert opinion pieces, and primary research articles, the NRS response scale was most often recommended in these guidance documents. When reviewing the empirical basis for these recommendations, we found that the NRS had slightly superior measurement properties (e.g., reliability, validity, responsiveness) across a wide variety of contexts of use as compared to other response scales. Conclusions Both empirical studies and review articles provide evidence that the 11-point NRS is likely the optimal response scale to evaluate pain among adult patients without cognitive impairment

Relationships between area-level socioeconomic status and urbanization with active transportation, independent mobility, outdoor time, and physical activity among Canadian children

Background: Active transportation (AT), independent mobility (IM), and outdoor time are promising ways to increase children’s physical activity. However, in order to create interventions to increase those forms of physical activity, it is important to understand the relationships between area-level socioeconomic status (SES) and type of urbanization with AT, IM, outdoor time, and physical activity, and this was the aim of the study. Methods: One thousand six hundred ninety-nine children in grades 4 to 6 (mean age: 10.2 ± 1.0 years) from three Canadian regions participated. AT, IM, and outdoor time were assessed using questionnaires and physical activity was measured using the SC-StepRX pedometer. Area-level SES was assessed using the median household income of the census tract in which the school was located and type of urbanization was determined for each school using standardized procedures. Generalized linear and general linear mixed models were used to examine the relationships. Results: Area-level SES and the type of urbanization were generally not related to AT, IM, or physical activity for either gender. However, we observed that both boys and girls living in lower SES areas had decreased odds of spending > 2 h outdoors on weekend days compared to their peers from higher SES areas. Girls living in suburban or rural areas were more likely to spend > 2 h outdoors on weekdays compared to their urban counterparts. Conclusions: AT, IM, and physical activity are generally not associated with area-level SES or the type of urbanization in this sample of Canadian children. The finding regarding outdoor time showing that both boys and girls of lower SES areas had decreased odds of spending > 2 h outdoors on weekends compared to their peers from higher SES areas suggest that additional efforts should be implemented to offer outdoor play opportunities in lower SES areas.Education, Faculty ofNon UBCKinesiology, School ofReviewedFacult

Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

Sex steroid hormones are synthesized from cholesterol and exert pleiotropic effects notably in the central nervous system. Pioneering studies from Baulieu and colleagues have suggested that steroids are also locally-synthesized in the brain. Such steroids, called neurosteroids, can rapidly modulate neuronal excitability and functions, brain plasticity, and behavior. Accumulating data obtained on a wide variety of species demonstrate that neurosteroidogenesis is an evolutionary conserved feature across fish, birds, and mammals. In this review, we will first document neurosteroidogenesis and steroid signaling for estrogens, progestagens, and androgens in the brain of teleost fish, birds, and mammals. We will next consider the effects of sex steroids in homeostatic and regenerative neurogenesis, in neuroprotection, and in sexual behaviors. In a last part, we will discuss the transport of steroids and lipoproteins from the periphery within the brain (and vice-versa) and document their effects on the blood-brain barrier (BBB) permeability and on neuroprotection. We will emphasize the potential interaction between lipoproteins and sex steroids, addressing the beneficial effects of steroids and lipoproteins, particularly HDL-cholesterol, against the breakdown of the BBB reported to occur during brain ischemic stroke. We will consequently highlight the potential anti-inflammatory, anti-oxidant, and neuroprotective properties of sex steroid and lipoproteins, these latest improving cholesterol and steroid ester transport within the brain after insults

A small component of the endoplasmic reticulum is required for store-operated Ca2+ channel activation in liver cells: evidence from studies using TRPV1 and taurodeoxycholic acid

Copyright © The Authors Journal compilation © 2009 Biochemical SocietyThe question of whether the activation of SOCs (store-operated Ca(2+) channels) requires the whole or part of the ER (endoplasmic reticulum) has not been fully resolved. The role of a putative sub-compartment of the ER in SOC activation in liver cells was investigated using ectopically expressed TRPV1 (transient receptor potential vanilloid 1), a non-selective cation channel, and TDCA (taurodeoxycholic acid), an activator of SOCs, to release Ca(2+) from different regions of the ER. TRPV1 was expressed in the ER and in the plasma membrane. The amount of Ca(2+) released from the ER by a TRPV1 agonist, measured using fura-2, was the same as that released by a SERCA (sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase) inhibitor, indicating that TRPV1 agonist-sensitive stores substantially overlap with SERCA inhibitor-sensitive stores. In contrast with SERCA inhibitors, TRPV1 agonists did not activate store-operated Ca(2+) entry. These findings were confirmed by patch-clamp recording. Using FFP-18, it was shown that SERCA inhibitors release Ca(2+) from the ER located closer to the plasma membrane than the region from which TRPV1 agonists release Ca(2+). In contrast with SERCA inhibitors, TRPV1 agonists did not induce a redistribution of STIM1 (stromal interaction molecule 1). TDCA caused the release of Ca(2+) from the ER, which was detected by FFP-18 but not by fura-2, and a redistribution of STIM1 to puncta similar to that caused by SERCA inhibitors. It is concluded that in liver cells, Ca(2+) release from a small component of the ER located near the plasma membrane is required to induce STIM1 redistribution and SOC activation.Joel Castro, Edoardo C. Aromataris, Grigori Y. Rychkov and Greg J. Barrit