1,076 research outputs found
Language motivation in a reconfigured Europe: access, identity, autonomy
In this paper, I propose that we need to develop an appropriate set of conceptual tools for examining motivational issues pertaining to linguistic diversity, mobility and social integration in a rapidly changing and expanding Europe. I begin by drawing on research that has begun to reframe the concept of integrative motivation in the context of theories of self and identity. Expanding the notion of identity, I discuss the contribution of the Council of Europe's European Language Portfolio in promoting a view of motivation as the development of a plurilingual European identity and the enabling of access and mobility across a multilingual Europe. Next, I critically examine the assumption that the individual pursuit of a plurilingual identity is unproblematic, by highlighting the social context in which motivation and identity are constructed and embedded. To illuminate the role of this social context, I explore three inter-related theoretical frameworks: poststructuralist perspectives on language motivation as 'investment'; sociocultural theory; and theories of autonomy in language education. I conclude with the key message that, as with autonomy, language motivation today has an inescapably political dimension of which we need to take greater account in our research and pedagogical practice
Dynamics of very low energy photoelectrons interacting with image charge of Cs/Cu(111) surface
Adult beginner distance language learner perceptions and use of assignment feedback
This qualitative study examines perceptions and use of assignment feedback among adult beginner modern foreign language learners on higher education distance learning courses. A survey of responses to feedback on assignments by 43 Open University students on beginner language courses in Spanish, French, and German indicated that respondents can be classified into three groups: those who use feedback strategically by integrating it into the learning process and comparing it with, for example, informal feedback from interaction with native speakers, those who take note of feedback, but seem not to use it strategically, and those who appear to take little account of either marks or feedback. The first group proved to be the most confident and most likely to maintain their motivation in the longer term. The conclusion discusses some of the pedagogical and policy implications of the findings
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The chaperone protein HSP47: a platelet collagen binding protein that contributes to thrombosis and haemostasis
Objective: Heat shock protein 47 (HSP47) is an intracellular chaperone protein that is vital for collagen biosynthesis in collagen secreting cells. This protein has also been shown to be present on the surface of platelets. Given the importance of collagen and its interactions with platelets in triggering haemostasis and thrombosis, in this study we sought to characterise the role of HSP47 on these cells.
Approach and Results: The deletion of HSP47 in mouse platelets or its inhibition in human platelets reduced their function in response to collagen and the GPVI agonist (CRP-XL), but responses to thrombin were unaltered. In the absence of functional HSP47, the interaction of collagen with platelets was reduced, and this was associated with reduced GPVI-collagen binding, signalling and platelet activation. Thrombus formation on collagen, under arterial flow conditions was also decreased following the inhibition or deletion of HSP47, in the presence or absence of the eptifibatide, consistent with a role for HSP47 in enhancing platelet adhesion to collagen. Platelet adhesion under flow to von Willebrand Factor was unaltered following HSP47 inhibition. Laser-induced thrombosis in cremaster muscle arterioles was reduced and bleeding time was prolonged in HSP47 deficient mice or following inhibition of HSP47.
Conclusions: Our study demonstrates the presence of HSP47 on the platelet surface where it interacts with collagen, stabilises platelet adhesion and increases collagen mediated signalling and therefore thrombus formation and haemostasis
Retarded PDI diffusion and a reductive shift in poise of the calcium depleted endoplasmic reticulum
Background: Endoplasmic reticulum (ER) lumenal protein thiol redox balance resists dramatic variation in unfolded protein load imposed by diverse physiological challenges including compromise in the key upstream oxidases. Lumenal calcium depletion, incurred during normal cell signaling, stands out as a notable exception to this resilience, promoting a rapid and reversible shift towards a more reducing poise. Calcium depletion induced ER redox alterations are relevant to physiological conditions associated with calcium signaling, such as the response of pancreatic cells to secretagogues and neuronal activity. The core components of the ER redox machinery are well characterized; however, the molecular basis for the calcium-depletion induced shift in redox balance is presently obscure. Results: In vitro, the core machinery for generating disulfides, consisting of ERO1 and the oxidizing protein disulfide isomerase, PDI1A, was indifferent to variation in calcium concentration within the physiological range. However, ER calcium depletion in vivo led to a selective 2.5-fold decline in PDI1A mobility, whereas the mobility of the reducing PDI family member, ERdj5 was unaffected. In vivo, fluorescence resonance energy transfer measurements revealed that declining PDI1A mobility correlated with formation of a complex with the abundant ER chaperone calreticulin, whose mobility was also inhibited by calcium depletion and the calcium depletion-mediated reductive shift was attenuated in cells lacking calreticulin. Measurements with purified proteins confirmed that the PDI1A-calreticulin complex dissociated as Ca2+ concentrations approached those normally found in the ER lumen ([Ca2+] K-0.5max = 190 mu M). Conclusions: Our findings suggest that selective sequestration of PDI1A in a calcium depletion-mediated complex with the abundant chaperone calreticulin attenuates the effective concentration of this major lumenal thiol oxidant, providing a plausible and simple mechanism for the observed shift in ER lumenal redox poise upon physiological calcium depletion.Wellcome Trust [Wellcome 084812/Z/08/Z]; European Commission (EU FP7 Beta-Bat) [277713]; Fundacao para a Ciencia e Tecnologia, Portugal [PTDC/QUI-BIQ/119677/2010]info:eu-repo/semantics/publishedVersio
Secondary recrystallization in Fe-3% Si alloy with (110)[001] single-component texture
Asymmetric rolling of interstitial-free steel using differential roll diameters. Part II : microstructure and annealing effects
The effects of annealing on the microstructure, texture, tensile properties, and R value evolution of an IF steel sheet after room-temperature symmetric and asymmetric rolling were examined. Simulations were carried out to obtain R values from the experimental textures using the viscoplastic self-consistent polycrystal plasticity model. The investigation revealed the variations in the textures due to annealing and symmetric/asymmetric rolling and showed that the R values correlate strongly with the evolution of the texture. An optimum heat treatment for the balance of strength, ductility, and deep drawability was found to be at 873 K (600 _C) for 30 minutes
Motivation for or from bilingual education? A comparative study of learner views in the Netherlands
Teaching and Teacher Learning (ICLON
Genetic Diversity of Staphylocoagulase Genes (coa): Insight into the Evolution of Variable Chromosomal Virulence Factors in Staphylococcus aureus
. Although SCs have been classified into 10 serotypes based on the differences in the antigenicity, genetic bases for their diversities and relatedness to chromosome types are poorly understood. type except for the cases of CC1 and CC8, which contained two and three different SC types, respectively. loci, resulting in the carriage of the combinations of allotypically different important virulence determinants in staphylococcal chromosome
Regulation of PERK Signaling and Leukemic Cell Survival by a Novel Cytosolic Isoform of the UPR Regulator GRP78/BiP
The unfolded protein response (UPR) is an evolutionarily conserved mechanism to allow cells to adapt to stress targeting the endoplasmic reticulum (ER). Induction of ER chaperone GRP78/BiP increases protein folding capacity; as such it represents a major survival arm of UPR. Considering the central importance of the UPR in regulating cell survival and death, evidence is emerging that cells evolve feedback regulatory pathways to modulate the key UPR executors, however, the precise mechanisms remain to be elucidated. Here, we report the fortuitous discovery of GRP78va, a novel isoform of GRP78 generated by alternative splicing (retention of intron 1) and alternative translation initiation. Bioinformatic and biochemical analyses revealed that expression of GRP78va is enhanced by ER stress and is notably elevated in human leukemic cells and leukemia patients. In contrast to the canonical GRP78 which is primarily an ER lumenal protein, GRP78va is devoid of the ER signaling peptide and is cytosolic. Through specific knockdown of endogenous GRP78va by siRNA without affecting canonical GRP78, we showed that GRP78va promotes cell survival under ER stress. We further demonstrated that GRP78va has the ability to regulate PERK signaling and that GRP78va is able to interact with and antagonize PERK inhibitor P58IPK. Our study describes the discovery of GRP78va, a novel cytosolic isoform of GRP78/BiP, and the first characterization of the modulation of UPR signaling via alternative splicing of nuclear pre-mRNA. Our study further reveals a novel survival mechanism in leukemic cells and other cell types where GRP78va is expressed
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