Inhibition of endothelial cell migration by thrombospondin-1 type-1 repeats is mediated by β1 integrins

The anti-angiogenic effect of thrombospondin-1 has been shown to be mediated through binding of the type-1 repeat (TSR) domain to the CD36 transmembrane receptor. We now report that the TSR domain can inhibit VEGF-induced migration in human umbilical vein endothelial cells (HUVEC), cells that lack CD36. Moreover, we identified β1 integrins as a critical receptor in TSR-mediated inhibition of migration in HUVEC. Using pharmacological inhibitors of downstream VEGF receptor effectors, we found that phosphoinositide 3-kinase (PI3k) was essential for TSR-mediated inhibition of HUVEC migration, but that neither PLCγ nor Akt was necessary for this response. Furthermore, β1 integrins were critical for TSR-mediated inhibition of microvascular endothelial cells, cells that express CD36. Together, our results indicate that β1 integrins mediate the anti-migratory effects of TSR through a PI3k-dependent mechanism

Accommodating 'others'?: housing dispersed, forced migrants in the UK

Utilising insights from a qualitative study in the city of Leeds (UK), this paper considers issues related to the housing of dispersed forced migrants. The term 'dispersed forced migrants' is used here as a general label to include four groups of international migrants (i.e. refugees, asylum seekers, those with humanitarian protection status and failed asylum seekers) who have previously been dispersed, on a no choice basis, to a variety of locations across the UK under the requirements of the Immigration and Asylum Act (1999). The tiering of housing entitlement that exists within the generic population of dispersed forced migrants (a consequence of the particular socio-legal status assigned to individuals), and its role in rendering migrants susceptible to homelessness is outlined. The adequacy/standard of accommodation made available to forced migrants is also discussed. It is concluded that current arrangements fail to meet the basic housing needs of many forced migrants. Any future improvement in this situation will require a significant shift in government policy

Governance, forced migration and welfare

This paper explores the welfare of forced migrants (i.e. refugees, asylum-seekers, those with humanitarian leave to remain, and “failed asylum-seekers/overstayers”) at three linked levels. First, it considers the governance of forced migrants at a supranational (in this case European Union) level. Second, particularly, but not exclusively in the context of the UK, it considers the extent to which the welfare rights of forced migrants in EU member states have been subject to a process of “hollowing out” or “dispersal”. Third, utilizing data from a recently completed qualitative research project, the paper outlines the complex local systems of governance that exist in relation to the housing and social security rights of forced migrants in the UK. The consequences of these networks are highlighted

Complexity reduction and policy consensus: asylum seekers, the right to work, and the ‘pull factor’ thesis in the UK context

Since the early 2000s, asylum policy in Western states has become increasingly dominated by the concept of the ‘pull factor’—the idea that the economic rights afforded to asylum seekers can act as a migratory pull, and will have a bearing on the numbers of asylum applications received. The pull factor thesis has been widely discredited by researchers but remains powerful among policymakers. Through an analysis of the pull factor in the UK context, and drawing on insights from Cultural Political Economy, this article argues that the hegemony of the pull factor thesis is best understood as a ‘policy imaginary’ which has become sedimented through both discursive and extra-discursive practices and processes. The article offers a means of understanding how a common sense assumption—which is challenged by a large body of evidence—has come to dominate policymaking in a key area of concern for politicians and policymakers

Vasopressin acts as a synapse organizer in limbic regions by boosting PSD95 and GluA1 expression

Hypothalamic arginine vasopressin (AVP)-containing magnocellular neurosecretory neurons (AVPMNN) emit collaterals to synaptically innervate limbic regions influencing learning, motivational behaviour, and fear responses. Here, we characterize the dynamics of expression changes of two key determinants for synaptic strength, the postsynaptic density (PSD) proteins AMPAR subunit GluA1 and PSD scaffolding protein 95 (PSD95), in response to in vivo manipulations of AVPMNN neuronal activation state, or exposure to exogenous AVP ex vivo. Both long-term water deprivation in vivo, which powerfully upregulates AVPMNN metabolic activity, and exogenous AVP application ex vivo, in brain slices, significantly increased GluA1 and PSD95 expression as measured by western blotting, in brain regions reportedly receiving direct ascending innervations from AVPMNN (i.e., ventral hippocampus, amygdala and lateral habenula). By contrast, the visual cortex, a region not observed to receive AVPMNN projections, showed no such changes. Ex vivo application of V1a and V1b antagonists to ventral hippocampal slices ablated the AVP stimulated increase in postsynaptic protein expression measured by western blotting. Using a modified expansion microscopy technique, we were able to quantitatively assess the significant augmentation of PSD95 and GLUA1 densities in subcellular compartments in locus coeruleus tyrosine hydroxylase immunopositive fibres, adjacent to AVP axon terminals. Our data strongly suggest that the AVPMNN ascending system plays a role in the regulation of the excitability of targeted neuronal circuits through upregulation of key postsynaptic density proteins corresponding to excitatory synapses.Consejo Nacional de Ciencia y Tecnología, México CONACYT; National Institute of Mental Health; Universidad Nacional Aut onoma de México.http://wileyonlinelibrary.com/journal/jnehj2023Immunolog

Gratitude and hospitality: Tamil refugee employment in London and the conditional nature of integration

Healy, R. L. 2014. The definitive, peer-reviewed and edited version of this article is published in Environment and Planning A, 2014, 46(3), pp. 614-628, http:dx/doi.org/10.1068/a4655The policy of integration attempts to address different elements of exclusion, yet relatively little research has considered what integration means to the refugees themselves. This paper explores one key area for supporting integration: employment.ESRC PTA-030-2005-0082

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.Research supported by FAPESP (2010/11005-5 and 2010/04462) and CNPq (#471939/2010-2 and 483005/2012-6

A genealogy of hacking

Hacking is now a widely discussed and known phenomenon, but remains difficult to define and empirically identify because it has come to refer to many different, sometimes incompatible, material practices. This paper proposes genealogy as a framework for understanding hacking by briefly revisiting Foucault’s concept of genealogy and interpreting its perspectival stance through the feminist materialist concept of the situated observer. Using genealogy as a theoretical frame a history of hacking will be proposed in four phases. The first phase is the ‘pre-history’ of hacking in which four core practices were developed. The second phase is the ‘golden age of cracking’ in which hacking becomes a self-conscious identity and community and is for many identified with breaking into computers, even while non-cracking practices such as free software mature. The third phase sees hacking divide into a number of new practices even while old practices continue, including the rise of serious cybercrime, hacktivism, the division of Open Source and Free Software and hacking as an ethic of business and work. The final phase sees broad consciousness of state-sponsored hacking, the re-rise of hardware hacking in maker labs and hack spaces and the diffusion of hacking into a broad ‘clever’ practice. In conclusion it will be argued that hacking consists across all the practices surveyed of an interrogation of the rationality of information techno-cultures enacted by each hacker practice situating itself within a particular techno-culture and then using that techno-culture to change itself, both in changing potential actions that can be taken and changing the nature of the techno-culture itself

PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models

BACKGROUND: PG545 is a heparan sulfate (HS) mimetic that inhibits tumour angiogenesis by sequestering angiogenic growth factors in the extracellular matrix (ECM), thus limiting subsequent binding to receptors. Importantly, PG545 also inhibits heparanase, the only endoglycosidase which cleaves HS chains in the ECM. The aim of the study was to assess PG545 in various solid tumour and metastasis models