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Discs in the 6 Myr old cluster η Chamaeleontis were searched for emission from hot H2. Around the M3 star ECHA J0843.3−7905, we detect circumstellar gas orbiting at ∼2 au. If the gas is ultraviolet excited, the ro-vibrational line traces a hot gas layer supported by a disc of mass , similar to the minimum mass solar nebula. Such a gas reservoir at 6 Myr would promote the formation and the inwards migration of gas giant planets. [ABSTRACT FROM AUTHOR]

An abstract of the article "α Calcitonin Gene-Related Peptide (αCGRP) Plays a Protective Role in the Onset of Angiotensin-II Induced Hypertension and Vascular Inflammation/Remodelling," by S-J Smillie and colleagues is presented.

We present the results of a search for pure rotational molecular hydrogen emission from two pre-main-sequence stars, AB Aur and CQ Tau. Observations were made using MICHELLE, the mid-infrared echelle spectrometer at the United Kingdom Infrared Telescope. We found some evidence for emission in the J = 4 → 2 line in AB Aur, but no J = 3 → 1 line from either star. We derive upper limits on line flux which are significantly smaller than previous line flux estimates based on ISO observations. This suggests that the emission detected by ISO is extended on scales of at least 6 arcsec, and does not come from the disc as previously thought. [ABSTRACT FROM AUTHOR]

Plants have evolved a vast chemical cornucopia to support their sessile lifestyles. Man has exploited this natural resource since Neolithic times and currently plant-derived chemicals are exploited for a myriad of applications. However, plant sources of most high-value natural products (NPs) are not domesticated and therefore their production cannot be undertaken on an agricultural scale. Further, these plant species are often slow growing, their populations limiting, the concentration of the target molecule highly variable and routinely present at extremely low concentrations. Plant cell and organ culture constitutes a sustainable, controllable and environmentally friendly tool for the industrial production of plant NPs. Further, advances in cell line selection, biotransformation, product secretion, cell permeabilisation, extraction and scale-up, among others, are driving increases in plant NP yields. However, there remain significant obstacles to the commercial synthesis of high-value chemicals from these sources. The relatively recent isolation, culturing and characterisation of cambial meristematic cells (CMCs), provides an emerging platform to circumvent many of these potential difficulties. [BMB Reports 2016; 49(3): 149-158].

Plant cell culture constitutes a sustainable, controllable and environmentally friendly tool to produce natural products for the pharmaceutical, cosmetic and industrial biotechnology industries. However, there are significant obstacles to the commercial synthesis of high value chemicals from plant culture including low yields, performance instability, slow plant cell growth, industrial scale-up and downstream processing. Cambial meristematic cells constitute a platform to ameliorate many of these potential problems enabling the commercial production of high value chemicals., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Plants are capable of producing a wide variety of secondary metabolites which have a diverse range of functions that can be exploited for medicinal purposes; for example, paclitaxel is a major anti-cancer drug found in the bark of Taxus spp. There are however supply issues as the compound is only found at low concentrations (0.05%) within the plant. The complex paclitaxel biosynthetic pathway makes chemical synthesis non-commercially viable; therefore alternative biotechnological sources have been explored for production including heterologous expression systems and plant cell culture., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Background: Scleroderma (SSc) is a complex autoimmune disorder that can be characterised by the presence 2of circulating autoantibodies to nuclear, cytoplasmic and cell surface antigens. In particular antibodies directed against endothelial cell antigens (anti-endothelial cell antibodies; AECA) have been detected. ICAM-1 is an adhesion molecule expressed on the surface of human endothelial cells. We have previously shown that cross-linking ICAM-1 with monoclonal antibodies leads to pro-inflammatory activation of human endothelial and vascular smooth muscle cells and that cardiac transplant recipients with transplant associated vasculopathy make antibodies directed against ICAM-1., Objectives: To determine whether SSc patients make antibodies directed against ICAM-1 and whether these antibodies induce pro-inflammatory activation of human endothelial cells in vitro., Methods: Using recombinant ICAM-1 as capture antigen, an ELISA was developed to measure ICAM-1 antibodies in sera from SSc patients. Antibodies were purified using ICAM-1 micro-affinity columns. HUVEC were incubated with purified anti-ICAM-1 antibodies and generation of reactive oxygen species, and expression of VCAM-1 was measured., Results: Significantly elevated levels of anti-ICAM-1 antibodies were detected in patients with diffuse (dSSc; 10/31 32%) or limited (lSSc; 14/36 39%) scleroderma. Cross-linking of HUVEC with purified anti-ICAM-1 antibodies caused a significant increase in ROS production (2.471±0.408 fold increase above untreated after 150 min p<0.001), and significant increase in VCAM-1 expression (10.6±1.77% vs 4.12±1.33%, p<0.01)., Conclusion: AECA from SSc patients target specific endothelial antigens including ICAM-1, and cause pro-inflammatory activation of human endothelial cells, suggesting that they are not only a marker of disease but that they contribute to its progression., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The transient receptor potential vanilloid 1 (TRPV1) is primarily localized to sensory nerve fibers and is associated with the stimulation of pain and inflammation. TRPV1 knockout (TRPV1KO) mice show enhanced LPS-induced sepsis compared with wild type (WT). This implies that TRPV1 may have a key modulatory role in increasing the beneficial and reducing the harmful components in sepsis. We investigated immune and inflammatory mechanisms in a cecal ligation and puncture (CLP) model of sepsis over 24 h. CLP TRPV1KO mice exhibited significant hypothermia, hypotension, and organ dysfunction compared with CLP WT mice. Analysis of the inflammatory responses at the site of initial infection (peritoneal cavity) revealed that CLP TRPV1KO mice exhibited: 1) decreased mononuclear cell integrity associated with apoptosis, 2) decreased macrophage tachykinin NK(1)-dependent phagocytosis, 3) substantially decreased levels of nitrite (indicative of NO) and reactive oxygen species, 4) increased cytokine levels, and 5) decreased bacteria clearance when compared with CLP WT mice. Therefore, TRPV1 deletion is associated with impaired macrophage-associated defense mechanisms. Thus, TRPV1 acts to protect against the damaging impact of sepsis and may influence the transition from local to a systemic inflammatory state.

Fibrosis is excessive scarring caused by the accumulation of extracellular matrix proteins and is a common end pathway in many chronic diseases. Endothelin-1 is a possible contributor to the persistent fibrotic phenotype of fibroblasts isolated from fibrotic lesions. In this report we used a specific dual endothelin A/B receptor antagonist, bosentan, to determine the role of endogenous endothelin signaling in maintaining the profibrotic phenotype of lung fibroblasts from scleroderma patients. Bosentan treatment of lung fibroblasts cultured from normal individuals and individuals with scleroderma was assessed using Affymetrix genome-wide expression profiling, real-time polymerase chain reaction and Western blot analysis and revealed that approximately one-third of the transcripts elevated greater than two-fold in fibrotic fibroblasts were reduced by Bosentan treatment. Genes whose overexpression in fibrotic fibroblasts that were dependent on endogenous endothelin signaling included the matrix or matrix-associated genes type I collagen, fibronectin and CCN2. The elevated adhesive property of fibrotic fibroblasts was also reduced by endothelin receptor antagonism. Basal expression of collagen, fibronectin and CCN2 and adhesion to matrix was not affected. Thus endogenous endothelin signaling contributes to the fibrotic phenotype of fibrotic fibroblasts, suggesting that antagonizing endothelin receptors may be of benefit in combating fibrotic disease.

The signal transduction mechanisms generating pathological fibrosis are almost wholly unknown. Endothelin-1 (ET-1), which is up-regulated during tissue repair and fibrosis, induces lung fibroblasts to produce and contract extracellular matrix. Lung fibroblasts isolated from scleroderma patients with chronic pulmonary fibrosis produce elevated levels of ET-1, which contribute to the persistent fibrotic phenotype of these cells. Transforming growth factor beta (TGF-beta) induces fibroblasts to produce and contract matrix. In this report, we show that TGF-beta induces ET-1 in normal and fibrotic lung fibroblasts in a Smad-independent ALK5/c-Jun N-terminal kinase (JNK)/Ap-1-dependent fashion. ET-1 induces JNK through TAK1. Fibrotic lung fibroblasts display constitutive JNK activation, which was reduced by the dual ETA/ETB receptor inhibitor, bosentan, providing evidence of an autocrine endothelin loop. Thus, ET-1 and TGF-beta are likely to cooperate in the pathogenesis of pulmonary fibrosis. As elevated JNK activation in fibrotic lung fibroblasts contributes to the persistence of the myofibroblast phenotype in pulmonary fibrosis by promoting an autocrine ET-1 loop, targeting the ETA and ETB receptors or constitutive JNK activation by fibrotic lung fibroblasts is likely to be of benefit in combating chronic pulmonary fibrosis.

Background: Transforming growth factor beta (TGFbeta), a multifunctional cytokine, plays a crucial role in the accumulation of extracellular matrix components in lung fibrosis, where lung fibroblasts are considered to play a major role. Even though the effects of TGFbeta on the gene expression of several proteins have been investigated in several lung fibroblast cell lines, the global pattern of response to this cytokine in adult lung fibroblasts is still unknown., Methods: We used Affymetrix oligonucleotide microarrays U95v2, containing approximately 12,000 human genes, to study the transcriptional profile in response to a four hour treatment with TGFbeta in control lung fibroblasts and in fibroblasts from patients with idiopathic and scleroderma-associated pulmonary fibrosis. A combination of the Affymetrix change algorithm (Microarray Suite 5) and of analysis of variance models was used to identify TGFbeta-regulated genes. Additional criteria were an average up- or down- regulation of at least two fold., Results: Exposure of fibroblasts to TGFbeta had a profound impact on gene expression, resulting in regulation of 129 transcripts. We focused on genes not previously found to be regulated by TGFbeta in lung fibroblasts or other cell types, including nuclear co-repressor 2, SMAD specific E3 ubiquitin protein ligase 2 (SMURF2), bone morphogenetic protein 4, and angiotensin II receptor type 1 (AGTR1), and confirmed the microarray results by real time-PCR. Western Blotting confirmed induction at the protein level of AGTR1, the most highly induced gene in both control and fibrotic lung fibroblasts among genes encoding for signal transduction molecules. Upregulation of AGTR1 occurred through the MKK1/MKK2 signalling pathway. Immunohistochemical staining showed AGTR1 expression by lung fibroblasts in fibroblastic foci within biopsies of idiopathic pulmonary fibrosis., Conclusions: This study identifies several novel TGFbeta targets in lung fibroblasts, and confirms with independent methods the induction of angiotensin II receptor type 1, underlining a potential role for angiotensin II receptor 1 antagonism in the treatment of lung fibrosis.

Objectives: To test the hypothesis that interpersonal problem-solving performance in older adults with a recent episode of parasuicide is poorer than that of depressed patients and community controls., Design: A cross-sectional design was used to assess differences between older parasuicidal patients, depressed patients, and community controls in interpersonal problem solving performance., Method: An existing outcome measure of interpersonal problem-solving, the Means End Problem-Solving (MEPS) procedure, was modified in order to make it more suitable for older adults. It was then administered to 18 older adults with an episode of parasuicide in the previous 14 days, 18 older adults who were being treated for clinical depression, and 22 older adults attending community groups. Comparisons between the groups in terms of performance on the MEPS were made., Results: When level of depression was controlled for, parasuicidal patients were poorer at generating relevant means of reaching given outcomes to interpersonal problems than community controls. There was no difference between the parasuicidal and depressed groups in terms of relevancy scores. There were no significant differences between groups in terms of other MEPS outcome variables., Conclusions: Parasuicide in older adults is related to a deficit in interpersonal problem solving performance that cannot be completely explained in terms of depression. Further investigation of interpersonal problem-solving in relation to parasuicide and depression in older adults is required, perhaps using process measures of interpersonal problem solving to clarify the nature of the difficulties. The modified MEPS is acceptable to older adults and can be easily administered.

Objective: TSG-6 [the product of tumor necrosis factor (TNF)-stimulated gene-6] is a hyaluronan-binding protein that is present in the synovial fluids of arthritis patients and is secreted by cells of articular joints (e.g. chondrocytes and synoviocytes). This study examines the pattern of TSG-6 expression in normal and diseased cartilage and synovium using immunohistochemical techniques., Design: A polyclonal antibody was raised against recombinant Link module from human TSG-6 and used to detect the protein in tissue sections taken from osteoarthritis (OA) and rheumatoid arthritis (RA) patients and controls., Results: There was no TSG-6 detected in normal tissues. In all OA synovium there was intense TSG-6 expression throughout the intimal layer, whereas in RA staining in this region was generally less pronounced and was absent at the synovial surface in tissues exhibiting significant inflammation. In RA TSG-6 was also expressed by infiltrating leukocytes and by cells at the cartilage-synovium pannus junction. TSG-6 immunoreactivity was present in the tunica intima of blood vessels in OA subintima, being particularly noticeable in the thickened smooth muscle of inflamed vessel walls, but was mostly confined to the lumen of the vessel in RA. In cartilage the majority of chondrocytes expressed TSG-6 in both OA and RA, usually with extensive staining in the surrounding matrix., Conclusion: TSG-6 is present within synovium and cartilage of arthritic joints, but not normal controls, and is synthesized by the resident cells. The pattern of TSG-6 expression is consistent with its proposed roles in extracellular matrix (ECM) remodeling and cellular proliferation.