HIV Activates the Tyrosine Kinase Hck to Secrete ADAM Protease-Containing Extracellular Vesicles

HIV-Nef activates the myeloid cell-typical tyrosine kinase Hck, but its molecular role in the viral life cycle is not entirely understood. We found that HIV plasma extracellular vesicles (HIV pEV) containing/10 proteases and Nef also harbor Hck, and analyzed its role in the context of HIV pEV secretion. Myeloid cells required Hck for the vesicle-associated release of ADAM17. This could be induced by the introduction of Nef and implied that HIV targeted Hck for vesicle-associated ADAM17 secretion from a myeloid compartment. The other contents of HIV-pEV, however, including miRNA and effector protein profiles, as well as the presence of haptoglobin suggested hepatocytes as a possible cellular source. HIV liver tissue analysis supported this assumption, revealing induction of Hck translation, evidence for ADAMprotease activation and HIV infection. Our findings suggest that HIV targets Hck to induce pro-inflammatory vesicles release and identifies hepatocytes as a possible host cell compartment. (c) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.Peer reviewe

Optimized Mouse Model for the Imaging of Tumor Metastasis upon Experimental Therapy

Peer reviewe

Basal cell carcinomas without histological confirmation and their treatment : an audit in four European regions

Summary- Background: Limited data are available on how often basal cell carcinomas (BCCs) are clinically diagnosed without histological confirmation and how they are treated. Objectives Within the framework of the EPIDERM project, an audit was conducted in four European countries to study the occurrence of clinically diagnosed BCCs without histological confirmation and to investigate how these are treated. Methods: In the Netherlands, Scotland, Finland and Malta studies were performed within different timeframes. Patients with one or more BCC(s) were selected and the number of clinically diagnosed BCCs without histological confirmation and their treatment was investigated by (manually) reviewing the (electronic) patient records and checking the (hospital) pathology databases to find evidence of histological confirmation. Results: In the Netherlands, 1089 patients with a first histologically confirmed BCC developed 1974 BCCs of which 1833 (92.9%) were histologically confirmed and 141 (7.1%) were not. A 4-month retrospective study conducted in Scotland selected 294 patients with 344 BCCs; 306 (89.0%) were histologically confirmed and 38 (11.0%) were not. A 3-month prospective study performed at the same centre in Scotland identified 44 patients who developed 58 BCCs; 44 (75.9%) of these were histologically confirmed and 14 (24.1%) were not. In Finland, there were 701 patients who developed 977 BCCs, of which 807 (82.6%) were histologically and 170 (17.4%) nonhistologically confirmed. In Malta, there were 420 patients with 477 BCCs. Only three (0.7%) of them were clinically diagnosed without histological confirmation. In the Netherlands and Finland, clinically diagnosed BCCs without histological confirmation were most often treated with cryotherapy, whereas in Scotland 5% imiquimod cream was the preferred treatment modality. Conclusions: Although the frequency of clinically diagnosed BCCs without histological confirmation differed between the four European regions (range 0.7-24.1%), this confirms that the burden of BCC in Europe is underestimated when based on data from pathology and/or cancer registries.peer-reviewe

Socially Included or Excluded? : The role of social capital among Filipino labor migrants

This article focuses on how social capital is mobilisable and usable for Filipino labour migrants in their efforts to become part of the Finnish labour market. Drawing on the argument of Anthias that not all kinds of resources enable social capital, this article also reveals the dominant role of the minority church as a provider of support simultaneously confining its members' inclusion to the destination society. The article demonstrates how mobilisation of social capital is possible only in certain socioeconomic context, for example, when social ties transfer usable resources for the actors, such as information and access to a new job, whereas in other cases, the social ties chiefly provide non-mobilisable resources, such as emotional support and solidarity. However, these resources can be of advantage for strengthening the ethnic identity of migrants.Peer reviewe

Welfare beyond Borders : Filipino Transnational Families’ Informal Social Protection Strategies

Remittances and caregiving arrangements are among the most significant practices of informal social protection against social risks and exclusion among transnational families. This article argues that remittances can provide social protection in cases where formal welfare services do not reach the citizens properly. Furthermore, it illustrates how members of Filipino transnational families can create sustainable informal social protection and utilise it long-term. The transnational practices are analysed to show how migrant capital, particularly the intersection of economic and social capital (Bourdieu, 1986), is transferred to informal social protection through meaningful reciprocity between the senders and recipients of remittances. Successful allocation of remittances and negotiation of care arrangements depend on the realisation of reciprocity and its social context, such as life circumstances, moral obligations and migrants’ personal goals for migration. The data draw on observations and 41 qualitative interviews conducted both in Finland and in the Philippines.Peer reviewe

Critical Social Inclusion of Adult Migrant Language Learners in Working Life: Experiences From SFI and LINC Programs

How can integration education programs facilitate the more seamless inclusion of migrant newcomers into working life and civil society? Traditionally, integration policy and practice have been framed within a nation‐state discourse in which views of migrant incorporation are grounded within a bordered nationalism embodying a native-migrant dichotomy that reifies the view of the "migrant other" as a subject defined by its "lack" in competence and agency. In our qualitative multiple case study, we explored the bridging potential of integration programs in facilitating the inclusion of migrant students within working life in Helsinki and Edmonton. We examined the "inclusectionalities," referring to the intersections of inclusion and exclusion that position adults enrolled in SFI (Swedish for Immigrants) and LINC (Language Instruction for Newcomers to Canada) language integration programs in the liminal spaces between belonging and othering. Guided by an understanding of critical social inclusion where migrants set the boundaries for interactions with authorities based upon their own needs and interests, we propose a transformational approach. Here migrant learners participate in a structural process where the fluid nature of social, political, and economic arrangements is consistently renegotiated on principles of egalitarianism and the full exercise of critical agency, herein envisioned as deliberate action resisting the social domination of racialized minorities by challenging and redefining institutional structures

ANKRD54 preferentially selects Bruton's Tyrosine Kinase (BTK) from a Human Src-Homology 3 (SH3) domain library

Bruton's Tyrosine Kinase (BTK) is a cytoplasmic protein tyrosine kinase with a fundamental role in B-lymphocyte development and activation. The nucleocytoplasmic shuttling of BTK is specifically modulated by the Ankyrin Repeat Domain 54 (ANKRD54) protein and the interaction is known to be exclusively SH3-dependent. To identify the spectrum of the ANKRD54 SH3-interactome, we applied phage-display screening of a library containing all the 296 human SH3 domains. The BTK-SH3 domain was the prime interactor. Quantitative western blotting analysis demonstrated the accuracy of the screening procedure. Revealing the spectrum and specificity of ANKRD54-interactome is a critical step toward functional analysis in cells and tissues.Peer reviewe

HIV-1 Nef Interacts with Inositol Trisphosphate Receptor to Activate Calcium Signaling in T Cells

HIV-1 pathogenicity factor Nef has been shown to modulate calcium signaling in host cells, but the underlying molecular mechanisms have remained unclear. Here we show that calcium/calcineurin-dependent activation of nuclear factor of activated T cells (NFAT) by Nef in Jurkat T cells requires the endoplasmic reticulum-resident inositol trisphosphate receptor (IP3R), but yet does not involve increase in phospholipase-Cγ1 (PLCγ1)-catalyzed production of IP3 or depletion of IP3-regulated intracellular calcium stores. Nef could be coprecipitated with endogenous IP3R type-1 (IP3R1) from Nef-transfected Jurkat T cells as well as from HIV-infected primary human peripheral mononuclear cells. Thus, the Nef/IP3R1-interaction defines a novel T cell receptor–independent mechanism by which Nef can promote T cell activation, and appears to involve atypical IP3R-triggered activation of plasma membrane calcium influx channels in a manner that is uncoupled from depletion of intracellular calcium stores

HIV-1 Infection of T cells and macrophages are differentially modulated by virion-associated Hck: a nef-dependent phenomenon

The proline repeat motif (PxxP) of Nef is required for interaction with the SH3 domains of macrophage-specific Src kinase Hck. However, the implication of this interaction for viral replication and infectivity in macrophages and T lymphocytes remains unclear. Experiments in HIV-1 infected macrophages confirmed the presence of a Nef:Hck complex which was dependent on the Nef proline repeat motif. The proline repeat motif of Nef also enhanced both HIV-1 infection and replication in macrophages, and was required for incorporation of Hck into viral particles. Unexpectedly, wild-type Hck inhibited infection of macrophages, but Hck was shown to enhance infection of primary T lymphocytes. These results indicate that the interaction between Nef and Hck is important for Nef-dependent modulation of viral infectivity. Hck-dependent enhancement of HIV-1 infection of T cells suggests that Nef-Hck interaction may contribute to the spread of HIV-1 infection from macrophages to T cells by modulating events in the producer cell, virion and target cell

Migrant Capital as a Resource for Migrant Communities

This thematic issue explores the processes and dynamics involved in how different forms of migrant capital are employed and how these relate to processes of social inclusion. Leaning on a Bourdieusian approach, we wish to move beyond existing descriptive studies and theorise the role migration plays in the accumulation, conversion and utilisation of various forms of capital by migrant communities and their members. The articles demonstrate how migrant capital can function as a resource created by migrants during the migration process, or as an outcome of it, and are potentially available to their family members. The articles illustrate via case studies from different national contexts how transnational migrants or members of migrant communities create, accumulate and employ diverse forms of capital in their efforts to achieve inclusion in destination and sending societies.This thematic issue explores the processes and dynamics involved in how different forms of migrant capital are employed and how these relate to processes of social inclusion. Leaning on a Bourdieusian approach, we wish to move beyond existing descriptive studies and theorise the role migration plays in the accumulation, conversion and utilisation of various forms of capital by migrant communities and their members. The articles demonstrate how migrant capital can function as a resource created by migrants during the migration process, or as an outcome of it, and are potentially available to their family members. The articles illustrate via case studies from different national contexts how transnational migrants or members of migrant communities create, accumulate and employ diverse forms of capital in their efforts to achieve inclusion in destination and sending societies.Non peer reviewe