Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel

Identifying risk factors for preeclampsia in subsequent pregnancies in women with a history of preeclampsia

Preeclampsia (PE) is a prevalent hypertensive disorder of pregnancy that causes significant maternal-fetal mortality. It has been reported that 60% of maternal mortality can be prevented. Studies have demonstrated that nursing has the ability to influence the mortality rates by providing proactive and competent care. Part of proactive, competent care is to identify those women at the highest risk for PE. Multiple studies have identified a history of PE as a significant risk factor for PE in future gestations. We conducted a nested case control study with our Rule Out Pre-Eclampsia (ROPE) cohort to identify comorbidities most likely to lead to recurrent PE

Impact of vasopressin receptors on regulation of immune response in preeclampsia

Preeclampsia is a common disorder of pregnancy resulting in increased blood pressure and end organ effects. The pathogenesis of preeclampsia is multi-factorial. Arginine vasopressin (AVP) is increased in preeclampsia, and the chronic infusion of AVP throughout gestation has previously been shown to be sufficient to produce a phenotype of preeclampsia in C57BL/6J mice representative of some of the cardiovascular and renal events seen in humans. Alterations in T-helper cell populations and their effector cytokines are also known to occur in preeclampsia. Therefore, we proposed that the increased secretion of AVP may be responsible for the immune changes that occur in preeclampsia. We also hypothesized that known pharmacological AVP antagonist, vaptans, may be able to reverse the effects of AVP infusion

Octopus-inspired adhesive skins for intelligent and rapidly switchable underwater adhesion

The octopus couples controllable adhesives with intricately embedded sensing, processing, and control to manipulate underwater objects. Current synthetic adhesive–based manipulators are typically manually operated without sensing or control and can be slow to activate and release adhesion, which limits system-level manipulation. Here, we couple switchable, octopus-inspired adhesives with embedded sensing, processing, and control for robust underwater manipulation. Adhesion strength is switched over 450× from the ON to OFF state in \u3c50 ms over many cycles with an actively controlled membrane. Systematic design of adhesive geometry enables adherence to nonideal surfaces with low preload and independent control of adhesive strength and adhesive toughness for strong and reliable attachment and easy release. Our bio-inspired nervous system detects objects and autonomously triggers the switchable adhesives. This is implemented into a wearable glove where an array of adhesives and sensors creates a biomimetic adhesive skin to manipulate diverse underwater objects

Autochthonous heritage languages and social media:writing and bilingual practices in Low German on Facebook

This article analyses how speakers of an autochthonous heritage language (AHL) make use of digital media, through the example of Low German, a regional language used by a decreasing number of speakers mainly in northern Germany. The focus of the analysis is on Web 2.0 and its interactive potential for individual speakers. The study therefore examines linguistic practices on the social network site Facebook, with special emphasis on language choice, bilingual practices and writing in the autochthonous heritage language. The findings suggest that social network sites such as Facebook have the potential to provide new mediatized spaces for speakers of an AHL that can instigate sociolinguistic change

Perceptions of institutional complexity and lobbyists’ decisions to join lobbying coalitions – evidence from the European Union context

YesWe use data from in-depth interviews with business lobbyists in Brussels to investigate why they choose to join lobbying coalitions. We find that lobbyists face two competing institutional incentives. First, they are confronted with incentives to ally with other European organisations, develop multilateral policy messages, and communicate messages to the Commission and the Parliament. Simultaneously, they face inducements to join narrower coalitions, develop bilateral policy messages, and direct those messages at the Council. Lobbyists’ receptivity to these incentives – and thus their choices of lobbying coalitions – differs with their age, educational background, and with the type and ownership structure of the organisations they represent. Combined, our findings contribute to the limited, mainly American literature on interest coalitions by demonstrating that lobbyists operate in complex institutional environments, and that their interpretations of and reactions to institutional complexity are shaped by individual- and organisational-level factors

Cultural and Media Identity Among Latvian Migrants in Germany

This chapter explores how transnational media and culture impacts on the identity formation of recent Latvian migrants in Germany. In the context of the EU, Germany opened its labour market to the new EU countries rather late, when compared to other ‘old’ EU countries. This has had an effect on the composition of the group of Latvian migrants going to Germany, and their identities. In the light of this, this chapter examines how Latvian migrants in Germany feel and experience their belonging to Latvia and its culture. It analyses the social and communicative practices crucial for the development of belonging, including the rootedness in the country where they live and the cultural references that are important for them. The evidence for the analysis in this chapter comes from in-depth interviews, open media diaries and network maps of Latvian migrants in Germany. The chapter situates the description of evidence in the framework of cultural identity concepts and discusses the role of culture and media in the process of building migrant identity. The chapter argues that culture is shaping the transnational self-perception of Latvian migrants in Germany – as it provides collective narratives of imagined common frames of references, and confirms feelings of belonging and distinction

Edge restenosis: impact of low dose irradiation on cell proliferation and ICAM-1 expression

BACKGROUND: Low dose irradiation (LDI) of uninjured segments is the consequence of the suggestion of many authors to extend the irradiation area in vascular brachytherapy to minimize the edge effect. Atherosclerosis is a general disease and the uninjured segment close to the intervention area is often atherosclerotic as well, consisting of neointimal smooth muscle cells (SMC) and quiescent monocytes (MC). The current study imitates this complex situation in vitro and investigates the effect of LDI on proliferation of SMC and expression of intercellular adhesion molecule-1 (ICAM-1) in MC. METHODS: Plaque tissue from advanced primary stenosing lesions of human coronary arteries (9 patients, age: 61 ± 7 years) was extracted by local or extensive thrombendarterectomy. SMC were isolated and identified by positive reaction with smooth muscle α-actin. MC were isolated from buffy coat leukocytes using the MACS cell isolation kit. For identification of MC flow-cytometry analysis of FITC-conjugated CD68 and CD14 (FACScan) was applied. SMC and MC were irradiated using megavoltage photon irradiation (CLINAC2300 C/D, VARIAN, USA) of 6 mV at a focus-surface distance of 100 cm and a dose rate of 6 Gy min(-1 )with single doses of 1 Gy, 4 Gy, and 10 Gy. The effect on proliferation of SMC was analysed at day 10, 15, and 20. Secondly, total RNA of MC was isolated 1 h, 2 h, 3 h, and 4 h after irradiation and 5 μg of RNA was used in standard Northern blot analysis with ICAM-1 cDNA-probes. RESULTS: Both inhibitory and stimulatory effects were detected after irradiation of SMC with a dose of 1 Gy. At day 10 and 15 a significant antiproliferative effect was found; at day 20 after irradiation cell proliferation was significantly stimulated. Irradiation with 4 Gy and 10 Gy caused dose dependent inhibitory effects at day 10, 15, and 20. Expression of ICAM-1 in human MC was neihter inhibited nor stimulated by LDI. CONCLUSION: Thus, the stimulatory effect of LDI on SMC proliferation at day 20 days after irradiation may be the in vitro equivalent of a beginning edge effect. Extending the irradiation area in vascular brachytherapy in vivo may therefore merely postpone and not inhibit the edge effect. The data do not indicate that expression of ICAM-1 in quiescent MC is involved in the process

Between mediatisation and politicisation: The changing role and position of Whitehall press officers in the age of political spin

Despite widespread critiques of ‘political spin’, the way governments engage with the mass media has attracted relatively little empirical attention. There is a small but growing body of research into bureaucracies’ responses to mediatisation from within which have identified tensions between bureaucratic and party political values, but this has not included the United Kingdom. There are concerns that the traditional dividing line between government information and political propaganda has come under increasing pressure as a higher premium is placed on persuasion by both journalists and politicians battling for public attention in an increasingly competitive market. Within Whitehall, the arrival of Labour in 1997 after 18 years in opposition was a watershed for UK government communications, allowing the government to reconfigure its official information service in line with the party political imperative to deploy strategic communications as a defence against increasingly invasive media scrutiny. Public relations, in government as elsewhere, has grown in scale, scope and status, becoming institutionalised and normalised within state bureaucracies, but how has this affected the role, status and influence of the civil servants who conduct media management? Within the system of executive self-regulation of government publicity that is characteristic of Whitehall, government press officers must negotiate a difficult path between the need to inform citizens about the government’s programme, and demands by ministers to deploy privileged information to secure and maintain personal and party advantage in the struggle for power. Taking 1997 as a turning point, and through the voices of the actors who negotiate government news – mainly press officers, but also journalists and special advisers – this article examines the changing role and position of Whitehall press officers in what has become known as the age of political spin, finding that profound and lasting change in the rules of engagement has taken place and is continuing