Receptor protein tyrosine kinase EphB4 is up-regulated in colon cancer

BACKGROUND: We have used commercially available cDNA arrays to identify EphB4 as a gene that is up-regulated in colon cancer tissue when compared with matched normal tissue from the same patient. RESULTS: Quantitative RT-PCR analysis of the expression of the EphB4 gene has shown that its expression is increased in 82% of tumour samples when compared with the matched normal tissue from the same patient. Using immunohistochemistry and Western analysis techniques with an EphB4-specific antibody, we also show that this receptor is expressed in the epithelial cells of the tumour tissue and either not at all, or in only low levels, in the normal tissue. CONCLUSION: The results presented here supports the emerging idea that Eph receptors play a role in tumour formation and suggests that further elucidation of this signalling pathway may identify useful targets for cancer treatment therapies

Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis

Background - The negative feedback system is an important physiological regulatory mechanism controlling angiogenesis. Soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), acts as a potent endogenous soluble inhibitor of VEGF- and placenta growth factor (PlGF)-mediated biological function and can also form dominant-negative complexes with competent full-length VEGF receptors. Methods and results - Systemic overexpression of VEGF-A in mice resulted in significantly elevated circulating sFlt-1. In addition, stimulation of human umbilical vein endothelial cells (HUVEC) with VEGF-A, induced a five-fold increase in sFlt-1 mRNA, a time-dependent significant increase in the release of sFlt-1 into the culture medium and activation of the flt-1 gene promoter. This response was dependent on VEGF receptor-2 (VEGFR-2) and phosphoinositide-3'-kinase signalling. siRNA-mediated knockdown of sFlt-1 in HUVEC stimulated the activation of endothelial nitric oxide synthase, increased basal and VEGF-induced cell migration and enhanced endothelial tube formation on growth factor reduced Matrigel. In contrast, adenoviral overexpression of sFlt-1 suppressed phosphorylation of VEGFR-2 at tyrosine 951 and ERK-1/-2 MAPK and reduced HUVEC proliferation. Preeclampsia is associated with elevated placental and systemic sFlt-1. Phosphorylation of VEGFR-2 tyrosine 951 was greatly reduced in placenta from preeclamptic patients compared to gestationally-matched normal placenta. Conclusion - These results show that endothelial sFlt-1 expression is regulated by VEGF and acts as an autocrine regulator of endothelial cell function

Central exclusive production of longlived gluinos at the LHC

We examine the possibility of producing gluino pairs at the LHC via the exclusive reaction pp -> p+gluino+gluino+p in the case where the gluinos are long lived. Such long lived gluinos are possible if the scalar super-partners have large enough masses. We show that it may be possible to observe the gluinos via their conversion to R-hadron jets and measure their mass to better than 1% accuracy for masses below 350 GeV with 300/fb of data.Comment: 13 pages, 9 figures. Minor corrections to version

Organ-on-a-chip for studying immune cell adhesion to liver sinusoidal endothelial cells:the potential for testing immunotherapies and cell therapy trafficking

Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard of care for patients with advanced tumours, yet the majority remain resistant to this therapy and urgent approaches are needed to boost the efficacy of these agents. Targeting the liver endothelial cells, as the orchestrators of immune cell recruitment, within the tumour microenvironment of this highly vascular cancer could potentially boost immune cell infiltration. We demonstrate the successful culture of primary human liver endothelial cells in organ-on-a-chip technology followed by perfusion of peripheral blood mononuclear cells. We confirm, with confocal and multiphoton imaging, the capture and adhesion of immune cells in response to pro-inflammatory cytokines in this model. This multicellular platform sets the foundation for testing the efficacy of new therapies in promoting leukocyte infiltration across liver endothelium as well as a model for testing cell therapy, such as chimeric antigen receptor (CAR)-T cell, capture and migration across human liver endothelium

b→sγb \to s \gamma Decay in SU(2)L×SU(2)R×U(1)SU(2)_L \times SU(2)_R \times U(1) Extensions of the Standard Model

The rare radiative decay $b \to s \gamma$ is studied in $SU(2)_L \times SU(2)_R \times U(1)$ extensions of the Standard Model. Matching conditions for coefficients of operators appearing in the low energy effective Hamiltonian for this process are derived, and QCD corrections to these coefficients are analyzed. The $b \to s \gamma$ decay rate is then calculated and compared with the corresponding Standard Model result. We find that observable deviations from Standard Model predictions can occur in $SU(2)_L \times SU(2)_R \times U(1)$ theories for a reasonable range of parameter values.Comment: 17 pages with 5 figures not included but available upon request, CALT-68-1893, TUM-T31-52/9

Angiopoietin-2 confers Atheroprotection in apoE-/- mice by inhibiting LDL oxidation via nitric oxide

Atherosclerosis is promoted by a combination of hypercholesterolemia and vascular inflammation. The function of Angiopoietin (Ang)-2, a key regulator of angiogenesis, in the maintenance of large vessels is unknown. A single systemic administration of Ang-2 adenovirus (AdAng-2) to apoE-/- mice fed a Western diet significantly reduced atherosclerotic lesion size 8 40%) and oxidized LDL and macrophage content of the plaques. These beneficial effects were abolished by the inhibition of nitric oxide synthase (NOS). In endothelial cells, endothelial NOS activation per se inhibited LDL oxidation and Ang-2 stimulated NO release in a Tie2-dependent manner to decrease LDL oxidation. These findings demonstrate a novel atheroprotective role for Ang-2 when endothelial cell function is compromised and suggest that growth factors, which stimulate NO release without inducing inflammation, could offer atheroprotection

The Evolution of Sunspot Magnetic Fields Associated with a Solar Flare

Solar flares occur due to the sudden release of energy stored in active-region magnetic fields. To date, the pre-cursors to flaring are still not fully understood, although there is evidence that flaring is related to changes in the topology or complexity of an active region's magnetic field. Here, the evolution of the magnetic field in active region NOAA 10953 was examined using Hinode/SOT-SP data, over a period of 12 hours leading up to and after a GOES B1.0 flare. A number of magnetic-field properties and low-order aspects of magnetic-field topology were extracted from two flux regions that exhibited increased Ca II H emission during the flare. Pre-flare increases in vertical field strength, vertical current density, and inclination angle of ~ 8degrees towards the vertical were observed in flux elements surrounding the primary sunspot. The vertical field strength and current density subsequently decreased in the post-flare state, with the inclination becoming more horizontal by ~7degrees. This behaviour of the field vector may provide a physical basis for future flare forecasting efforts.Comment: Accepted for Publication in Solar Physics. 16 pages, 4 figure

The 2dF-SDSS LRG and QSO Survey: The Star Formation Histories of Luminous Red Galaxies

We present a detailed investigation into the recent star formation histories of 5,697 Luminous Red Galaxies (LRGs) based on the Hdelta (4101A) and [OII] (3727A) lines. LRGs are luminous (L>3L*), galaxies which have been selected to have photometric properties consistent with an old, passively evolving stellar population. For this study we utilise LRGs from the recently completed 2dF-SDSS LRG and QSO survey (2SLAQ). Equivalent widths of the Hdelta and [OII] lines are measured and used to define three spectral types, those with only strong Hdelta absorption (k+a), those with strong [OII] in emission (em) and those with both (em+a). All other LRGs are considered to have passive star formation histories. The vast majority of LRGs are found to be passive (~80 per cent), however significant numbers of k+a (2.7 per cent), em+a (1.2 per cent) and em LRGs (8.6 per cent) are identified. An investigation into the redshift dependence of the fractions is also performed. A sample of SDSS MAIN galaxies with colours and luminosities consistent with the 2SLAQ LRGs is selected to provide a low redshift comparison. While the em and em+a fractions are consistent with the low redshift SDSS sample, the fraction of k+a LRGs is found to increase significantly with redshift. This result is interpreted as an indication of an increasing amount of recent star formation activity in LRGs with redshift. By considering the expected life time of the k+a phase, the number of LRGs which will undergo a k+a phase can be estimated. A crude comparison of this estimate with the predictions from semi-analytic models of galaxy formation shows that the predicted level of k+a and em+a activity is not sufficient to reconcile the predicted mass growth for massive early-types in a hierarchical merging scenario.Comment: Accepted for publication in MNRAS, 13 pages, 10 figure