This paper explores the motivations and meanings of international student mobility. Central to the discussion are the results of a large questionnaire survey and associated in-depth interviews with UK students enrolled in universities in six countries from around the world. The results suggest, first, that several different dimensions of social and cultural capital are accrued through study abroad. It is argued that the search for 'world class' education has taken on new significance. Second, the paper argues that analysis of student mobility should not be confined to a framework that separates study abroad from the wider life-course aspirations of students. It is argued that these insights go beyond existing theorisations of international student mobility to incorporate recognition of diverse approaches to difference within cultures of mobility, including class reproduction of distinction, broader notions of distinction within the life-plans of individual students, and how 'reputations' associated with educational destinations are structured by individuals, institutions and states in a global higher education system that produces differentially mediated geographies of international student mobility. key wordsinternational students higher education universities mobility globalisation difference

During recent decades there has been a change in the circulation of atmospheric pressure throughout the Northern Hemisphere. These variations are expressed in the recently described Arctic Oscillation (AO), which has shown an upward trend (associated with winter warming in the eastern Arctic) during the last three decades. We analysed a 12-year time series on growth of Cassiope tetragona (Lapland Cassiope) and a 21-year time series on abundance of a Svalbard reindeer population. High values of the AO index were associated with reduced plant growth and reindeer population growth rate. The North Atlantic Oscillation index was not able to explain a significant proportion of the variance in either plant growth or reindeer population fluctuations. Thus, the AO index may be a better predictor for ecosystem effects of climate change in certain high-arctic areas compared to the NAO index.

cDNAs encoding three splice variants of the P2X2 receptor were isolated from rat cerebellum. The first variant has a serine/proline-rich segment deleted from the intracellularly located carboxyl-terminal domain of the P2X2 subunit. The second and third variants have the splice site in the second half of the predicted first transmembrane domain. Either a 12-amino acid insertion or a six-amino acid deletion occurs at this position. cRNAs for these isoforms of the P2X2 subunit were injected into Xenopus laevis oocytes and tested for function. ATP evoked inward currents only with the splice variant [designated P2X2(b)] having the 69-amino acid deletion. The potencies of various agonists at the homomeric P2X2(b) receptor were not significantly different from those at the P2X2(a) homomeric channel. However, the P2X2(b) receptor showed significantly lower antagonist sensitivity. In contrast to the nondesensitizing P2X2(a) receptor, prolonged application of ATP produced a more rapid desensitization of the P2X2(b) receptor. When the P2X2(a) and P2X2(b) receptor responses were recorded in transfected mammalian cells, this difference was again found. The change in desensitization may be determined by proline/serine-rich segments and/or phosphorylation motifs that are removed from the tail region in formation of the P2X2(b) subunit. In situ hybridization of the three newly isolated isoforms of the P2X2 subunit was performed at the macroscopic and cellular levels; transcripts for two of them [P2X2(b) and p2x2(c)] but not the third [p2x2(d)], which carries the 12-amino acid addition, were present in many structures in the neonatal rat brain and on sensory and sympathetic ganglia. mRNA for the p2x2(d) splice variant was present only in the nodose ganglion, at a low level.

The EphA3 receptor tyrosine kinase preferentially binds ephrin-A5, a member of the corresponding subfamily of membrane-associated ligands. Their interaction regulates critical cell communication functions in normal development and may play a role in neoplasia. Here we describe a random mutagenesis approach, which we employed to study the molecular determinants of the EphA3/ephrin-A5 recognition. Selection and functional characterization of EphA3 point mutants with impaired ephrin-A5 binding from a yeast expression library defined three EphA3 surface areas that are essential for the EphA3/ephrin-A5 interaction. Two of these map to regions identified previously in the crystal structure of the homologous EphB2-ephrin-B2 complex as potential ligand/receptor interfaces. In addition, we identify a third EphA3/ephrin-A5 interface that falls outside the structurally characterized interaction domains. Functional analysis of EphA3 mutants reveals that all three Eph/ephrin contact areas are essential for the assembly of signaling-competent, oligomeric receptor-ligand complexes.Eph receptor tyrosine kinases (Ephs) 1 are activated through interaction with cell surface-bound ephrin proteins. Binding preferences and structural features classify eight type A Ephs interacting with six type A ephrins that attach to the membrane via glycophosphatidylinositol, as well as six type B Ephs interacting with corresponding type B transmembrane ephrins, which contain conserved cytoplasmic domains (1). Eph/ephrin contacts on opposing cells direct cell movements underlying developmental patterning events (2, 3) but may also regulate tumor cell positioning during cancer metastasis and invasion (4). In many cases Eph signaling results in cytoskeletal collapse, down-regulation of cell-cell adhesion proteins, and cell rounding (2, 5). Concurrent protease-mediated cleavage of the Eph/ephrin linkages (6) leads to cell-cell detachment and repulsion. Interestingly, Eph/ephrin interactions can also promote cell adhesion, a dichotomy of function that has been widely recognized (2,7,8).Ephs have a highly conserved domain structure throughout the animal kingdom (9). The extracellular domain (ECD) consists of a unique N-terminal globular structure, necessary and sufficient for ephrin binding (10, 11), followed by a cysteinerich linker, an EGF-like motif, and two type II fibronectin domains. For human EphA3 (12), these regions span amino acid sequence positions 29 -203, 204 -260, 271-324, 325-435, and 435-531, respectively. The minimal N-terminal globular domain has a ␤ jellyroll-like architecture (13), whereas structures of the cysteine-rich linker and adjoining EGF motif have not been solved to date.Clearly, all Eph/ephrin signaling is initiated by a 1:1 interaction between the globular Eph domain and a conserved Ephbinding domain of the ephrins (14). Furthermore, functional studies have indicated that biological responses rely on oligomerized ephrins to assemble active Eph receptor clusters capable of triggering downstream signaling cascades (15, 16)....

Eph receptor tyrosine kinases and their ligands (ephrins) are highly conserved protein families implicated in patterning events during development, particularly in the nervous system. In a number of functional studies, strict conservation of structure and function across distantly related vertebrate species has been confirmed. In this study we make use of the observation that soluble human EphA3 (HEK) exerts a dominant negative effect on somite formation and axial organization during zebrafish embryogenesis to probe receptor function. Based on exon structure we have dissected the extracellular region of EphA3 receptor into evolutionarily conserved subdomains and used kinetic BIAcore analysis, mRNA injection into zebrafish embryos, and receptor transphosphorylation analysis to study their function. We show that ligand binding is restricted to the N-terminal region encoded by exon III, and we identify an independent, C-terminal receptor-dimerization domain. Recombinant proteins encoding either region in isolation can function as receptor antagonists in zebrafish. We propose a two-step mechanism of Eph receptor activation with distinct ligand binding and ligandindependent receptor-receptor oligomerization events.The Eph family of receptors signal by binding cell-surface proteins known as ephrins. Cell contact is thought essential for this process, as only membrane-associated or artificially clustered forms of the ephrins, which mimic cell-cell apposition, can cause receptor transphosphorylation and activation (1-3). Inferred from sequence homologies, the structure of the Eph family is typified by an extracellular domain (ECD) 1 comprising an N-terminal, cysteine-rich region, an EGF-like motif, and two fibronectin III repeats (4 -6); however, the structural requirements and mechanism of receptor activation remain to be elucidated. Studies measuring Eph/ephrin binding affinities using artificially clustered receptor ECDs suggest that Eph receptors and ephrins fall into the following two groups: EphA receptors interact preferentially with glycosylphosphatidylinositollinked ephrins (ephrin-A), whereas those interacting preferentially with transmembrane ligands (ephrin-B) are called EphB receptors (7). Within each group, Eph receptors display crossreactivity with multiple ephrins (1, 8 -12). However, receptors and ligands within a class do not show equivalent affinities, but rather display a distinct ordering (3,(12)(13)(14). These findings are in keeping with the specialized roles in the development of the visual system, observed for EphA3 receptors (MEK4/CEK4) and ephrin-A2 (ELF1) and -A5 ligands (AL1/RAGS) (14 -18). Very similar functional and structural characteristics have been described for the zebrafish ephrin zEphL4, suggesting it as the orthologue of ephrin-A5 (19).The activation mechanisms for a number of other RTK subfamilies have been elucidated. These include dimerization/activation of individual class I receptor chains through conformational changes upon binding of soluble ligands, ligand-induced activatio...

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The EPH-like branch of receptor tyrosine kinases (RTKs) 1 has more than 28 members described in several vertebrate species (1-3). All were identified prior to the characterization of their cognate ligands by methods independent of a biological assays or specific physiological activity (2). As a consequence little is known about their specific functions. However, expression patterns of several EPH-like RTKs in embryogenesis, in particular in the nervous system, suggests a role in development (4, 5). Overexpression of some family members including HEK, EPH, ERK, and ECK in tumor-derived cell lines, tumor specimens, and transfected cells implicate these receptors in oncogenesis (6 -10).Recently we identified HEK on the cell surface of a pre-B acute lymphoblastic leukemia cell line, LK63, using the IIIA4 monoclonal antibody (mAb) (7). Immunofluorescence studies with IIIA4 revealed expression of HEK in blood samples from patients with acute leukemia, but not in normal adult tissues or blood cells (7, 11). In embryos, the expression patterns of the murine and chicken HEK homologues MEK 4 and CEK 4, and their recently identified ligand ELF1 (12) and RAGS (13), respectively, suggest a role in the development of the retinotectal projection map. We isolated a soluble HEK ligand from human placenta-conditioned medium using a biosensor-based affinity detection approach (14). The HEK ligand was identified by sequence homology as a soluble form of AL-1 (15), a member of the ligands for EPH-Related Kinases (LERKs) family (16,17) and for consistency with other members will be referred to as LERK 7. This family of transmembrane or membrane-associated proteins were isolated as potential ligands for EPH-like RTKs through their interactions with recombinant EPH receptor family exodomains (15, 18 -21). In most cases, bivalent Fc fusion proteins of either the receptor or the ligand were used for detecting potential binding partners. A requirement for membrane association of the ligand and the ability of more than one ligand to bind the same receptor with comparable affinity appeared to be characteristic of many of these ligands (21-25). However, soluble ligands for both ECK (26) and HEK (14) have been isolated from biological sources using receptor affinitybased protocols. Functional assays with the natural ligands leave some ambiguity about the absolute requirement for membrane association of the ligands for biological function (9,15,26,27). In addition to binding LERK7, a bivalent HEK fusion construct was shown to bind with significant affinity to LERK 1, 2 (18), LERK 3, 4 (28), and LERK 5 (24).Here we report the results of studies on the interaction between HEK and bivalent Fc-fusion proteins of LERKs 1 to 5 and LERK 7 or monovalent LERK3 and LERK7 produced as Flag-epitope tagged proteins. We use BIAcore technology, SE-HPLC, sedimentation equilibrium centrifugation, and functional assays which show that LERK 7 is the principal HEK

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