Do international institutions matter? Socialization and international bureaucrats

A key component of (neo-)functionalist and constructivist approaches to the study of international organizations concerns staff socialization. Existing analyses of how, or indeed whether, staff develop more pro-internationalist attitudes over time draw predominantly on cross-sectional data. Yet, such data cannot address (self-)selection issues or capture the inherently temporal nature of attitude change. This article proposes an innovative approach to the study of international socialization using an explicitly longitudinal design. Analysing two waves of a large-scale survey conducted within the European Commission in 2008 and 2014, it examines the beliefs and values of the same individuals over time and exploits exogenous organizational changes to identify causal effects. Furthermore, the article theorizes and assesses specified scope conditions affecting socialization processes. Showing that international institutions do, in fact, influence value acquisition by individual bureaucrats, our results contest the widely held view that international organizations are not a socializing environment. Our analysis also demonstrates that age at entry and gender significantly affect the intensity of such value change

Reactive intercalation and oxidation at the buried graphene-germanium interface

We explore a number of different electrochemical, wet chemical, and gas phase approaches to study intercalation and oxidation at the buried graphene-Ge interface. While the previous literature focused on the passivation of the Ge surface by chemical vapor deposited graphene, we show that particularly via electrochemical intercalation in a 0.25 N solution of anhydrous sodium acetate in glacial acetic acid, this passivation can be overcome to grow GeO2 under graphene. Angle resolved photoemission spectroscopy, Raman spectroscopy, He ion microscopy, and time-of-flight secondary ion mass spectrometry show that the monolayer graphene remains undamaged and its intrinsic strain is released by the interface oxidation. Graphene acts as a protection layer for the as-grown Ge oxide, and we discuss how these insights can be utilized for new processing approaches.We acknowledge financial support from the EPSRC (EP/K016636/1, EP/P51021X/1) and the Future Photonics Hub - Innovation Partnership Fund (EPSRC EP/L00044X/1). P.B.W. acknowledges EPSRC Cambridge NanoDTC EP/G037221/1. R.S.W. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme through a EU Marie Skłodowska-Curie Individual Fellowship (Global) under grant ARTIST (no. 656870). R.W. acknowledges EPSRC Doctoral Training Award (EP/M506485/1)

Pleomorphic adenoma of the vulva, clinical reminder of a rare occurrence

Pleomorphic adenoma, also known as mixed tumor, is a benign tumor which typically presents as a painless and persistent mass. The majority of pleomorphic adenomas involve the salivary glands, most commonly the parotid gland. Other sites include breast and skin. It is a rare tumor in the vulva. In this article we are reporting a case of pleomorphic adenoma of labia with characteristic pathologic and clinical findings, as reminder of a common benign neoplasm occurring with rare locality

Loss of the integrin-activating transmembrane protein Fam38A (Piezo1) promotes a switch to a reduced integrin-dependent mode of cell migration

Lung cancer is one of the most common fatal diseases in the developed world. The disease is rarely cured by currently available therapies, with an overall survival rate of ∼10%. Characterizing novel proteins that offer crucial insights into the processes of lung tumour invasion and metastasis may therefore provide much-needed prognostic markers, and influence therapeutic strategies. Aberrant function of the integrin family of heterodimeric cell surface receptors is a common theme in cancer--investigation into novel integrin activity regulators may offer crucial insights into the processes of tumour invasion and metastasis and may reveal insights into potential therapeutic targets. We previously described that depletion of the novel multi-transmembrane domain protein Fam38A, located at the endoplasmic reticulum (ER), inactivates endogenous beta1 integrin affinity, reducing cell adhesion. We now show that depletion of Fam38A, also now known as Piezo1, causes anchorage independence and a switch to a reduced integrin-dependent mode of cell migration/invasion, a novel phenotype for this integrin-regulating protein. Normal lung epithelial cells show increased rates of migration by 2D time-lapse microscopy and increased capacity to invade into matrigel, despite having decreased integrin affinity. We confirm greatly depleted Fam38A expression in small cell lung cancer (SCLC) lines where a form of reduced integrin-dependent migration, i.e. amoeboid migration, is a known phenotype. We propose that loss of Fam38A expression may cause increased cell migration and metastasis in lung tumours

Dissecting the Autocrine and Paracrine Roles of the CCR2-CCL2 Axis in Tumor Survival and Angiogenesis

The CCL2 CCR2 axis is likely to contributes to the development and progression of cancer diseases by two major mechanisms; autocrine effect of CCL2 as a survival/growth factor for CCR2+ cancer cells and, the attraction of CCR2+ CX3CR1+tumor associated macrophages that in the absence of CCR2 hardly migrate. Thus far no in vivo system has been set up to differentiate the selective contribution of each of these features to cancer development. Here we employed a chimera animal model in which all non-malignant cells are CCR2−/−, but all cancer cells are CCR2+, combined with an adoptive transfer system of bone marrow (BM) CX3CR1+ cells from CCR2+ mice harboring a targeted replacement of the CX3CR1gene by an enhanced green fluorescent protein (EGFP) reporter gene (cx3cr1gfp), together with the CD45.1 congene. Using this system we dissected the selective contribution of CX3CR1+CCR2+ cells, which comprise only about 7% of CD11b+ BM cells, to tumor development and angiogenesis. Showing that aside for their direct pro-angiogenic effect they are essential for the recruitment of other CD11b+ cells to the tumor site. We further show that the administration of CCR2-Ig, that selectively and specifically neutralize CCL2, to mice in which CCR2 is expressed only on tumor cells, further suppressed tumor development, implicating for the key role of this chemokine supporting tumor survival in an autocrine manner. This further emphasizes the important role of CCL2 as a target for therapy of cancer diseases

Intermediate predator naïveté and sex-skewed vulnerability predict the impact of an invasive higher predator

The spread of invasive species continues to reduce biodiversity across all regions and habitat types globally. However, invader impact prediction can be nebulous, and approaches often fail to integrate coupled direct and indirect invader effects. Here, we examine the ecological impacts of an invasive higher predator on lower trophic groups, further developing methodologies to more holistically quantify invader impact. We employ functional response (FR, resource use under different densities) and prey switching experiments to examine the trait- and density-mediated impacts of the invasive mosquitofish Gambusia affinis on an endemic intermediate predator Lovenula raynerae (Copepoda). Lovenula raynerae effectively consumed larval mosquitoes, but was naïve to mosquitofish cues, with attack rates and handling times of the intermediate predator unaffected by mosquitofish cue-treated water. Mosquitofish did not switch between male and female prey, consistently displaying a strong preference for female copepods. We thus demonstrate a lack of risk-reduction activity in the presence of invasive fish by L. raynerae and, in turn, high susceptibility of such intermediate trophic groups to invader impact. Further, we show that mosquitofish demonstrate sex-skewed predator selectivity towards intermediate predators of mosquito larvae, which may affect predator population demographics and, perversely, increase disease vector proliferations. We advocate the utility of FRs and prey switching combined to holistically quantify invasive species impact potential on native organisms at multiple trophic levels

Elevated Expression of Phospholipid Transfer Protein in Bone Marrow Derived Cells Causes Atherosclerosis

Background: Phospholipid transfer protein (PLTP) is expressed by various cell types. In plasma, it is associated with high density lipoproteins (HDL). Elevated levels of PLTP in transgenic mice result in decreased HDL and increased atherosclerosis. PLTP is present in human atherosclerosis lesions, where it seems to be macrophage derived. The aim of the present study is to evaluate the atherogenic potential of macrophage derived PLTP. Methods and Findings: Here we show that macrophages from human PLTP transgenic mice secrete active PLTP. Subsequently, we performed bone marrow transplantations using either wild type mice (PLTPwt/wt), hemizygous PLTP transgenic mice (huPLTPtg/wt) or homozygous PLTP transgenic mice (huPLTPtg/tg) as donors and low density lipoprotein receptor deficient mice (LDLR-/-) as acceptors, in order to establish the role of PLTP expressed by bone marrow derived cells in diet-induced atherogenesis. Atherosclerosis was increased in the huPLTPtg/wt → LDLR-/ - mice (2.3-fold) and even further in the huPLTPtg/tg→LDLR-/ - mice (4.5-fold) compared with the control PLTPwt/wt→LDLR-/- mice (both P<0.001). Plasma PLTP activity levels and non-HDL cholesterol were increased and HDL cholesterol decreased compared with controls (all P<0.01). PLTP was present in atherosclerotic plaques in the mice as demonstrated by immunohistochemistry and appears to co-localize with macrophages. Isolated macrophages from PLTP transgenic mice do not show differences in cholesterol efflux or in cytokine production. Lipopolysaccharide activation of macrophages results in increased production of PLTP. This effect was strongly amplified in PLTP transgenic macrophages. Conclusions: We conclude that PLTP expression by bone marrow derived cells results in atherogenic effects on plasma lipids, increased PLTP activity, high local PLTP protein levels in the atherosclerotic lesions and increased atherosclerotic lesion size

Rgs2 Mediates Pro-Angiogenic Function of Myeloid Derived Suppressor Cells in the Tumor Microenvironment via Upregulation of MCP-1

Tumor growth is intimately linked with stromal interactions. Myeloid derived suppressor cells (MDSCs) are dramatically elevated in cancer patients and tumor bearing mice. MDSCs modulate the tumor microenvironment through attenuating host immune response and increasing vascularization.In searching for molecular mediators responsible for pro-tumor functions, we found that regulator of G protein signaling-2 (Rgs2) is highly increased in tumor-derived MDSCs compared to control MDSCs. We further demonstrate that hypoxia, a common feature associated with solid tumors, upregulates the gene expression. Genetic deletion of Rgs2 in mice resulted in a significant retardation of tumor growth, and the tumors exhibit decreased vascular density and increased cell death. Interestingly, deletion of Rgs2 in MDSCs completely abolished their tumor promoting function, suggesting that Rgs2 signaling in MDSCs is responsible for the tumor promoting function. Cytokine array profiling identified that Rgs2-/- tumor MDSCs produce less MCP-1, leading to decreased angiogenesis, which could be restored with addition of recombinant MCP-1.Our data reveal Rgs2 as a critical regulator of the pro-angiogenic function of MDSCs in the tumor microenvironment, through regulating MCP-1 production