Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and β\u3csub\u3e2\u3c/sub\u3e-agonist use

Background Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this brake on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Methods Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β2-adrenergic receptor haplotype determination. Results Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Conclusion Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to β-agonist. The decreased phosphorylation does not appear to be associated with a particular β2-adrenergic receptor haplotype. The observed decrease in VASP phosphorylation suggests greater inhibition of actin reorganization which is necessary for altering attachment and migration required during epithelial repair

Long-term modifications of coastal defences enhance marine biodiversity

Realization that hard coastal infrastructures support lower biodiversity than natural habitats has prompted a wealth of research seeking to identify design enhancements offering ecological benefits. Some studies showed that artificial structures could be modified to increase levels of diversity. Most studies, however, only considered the short-term ecological effects of such modifications, even though reliance on results from short-term studies may lead to serious misjudgements in conservation. In this study, a seven-year experiment examined how the addition of small pits to otherwise featureless seawalls may enhance the stocks of a highly-exploited limpet. Modified areas of the seawall supported enhanced stocks of limpets seven years after the addition of pits. Modified areas of the seawall also supported a community that differed in the abundance of littorinids, barnacles and macroalgae compared to the controls. Responses to different treatments (numbers and size of pits) were species-specific and, while some species responded directly to differences among treatments, others might have responded indirectly via changes in the distribution of competing species. This type of habitat enhancement can have positive long-lasting effects on the ecology of urban seascapes. Understanding of species interactions could be used to develop a rule-based approach to enhance biodiversity

A Resolved Ring of Debris Dust around the Solar Analog HD 107146

We present resolved images of the dust continuum emission from the debris disk around the young (80-200 Myr) solar-type star HD 107146 with CARMA at λ = 1.3 mm and the CSO at λ = 350 μ. Both images show that the dust emission extends over an approximately 10" diameter region. The high-resolution (3") CARMA image further reveals that the dust is distributed in a partial ring with significant decrease in a flux inward of 97 AU. Two prominent emission peaks appear within the ring separated by ~140° in the position angle. The morphology of the dust emission is suggestive of dust captured into a mean motion resonance, which would imply the presence of a planet at an orbital radius of ~45-75 AU

Are working memory and glutamate concentrations involved in early-life stress and severity of psychosis?

Objective Occurrences of early‐life stress (ELS) are associated with the severity of psychotic symptoms and working memory (WM) deficits in patients with psychosis (PSY). This study investigated potential mediation roles of WM behavioral performance and glutamate concentrations in prefrontal brain regions on the association between ELS and psychotic symptom severity in PSY. Method Forty‐seven patients with PSY (established schizophrenia, n = 30; bipolar disorder, n = 17) completed measures of psychotic symptom severity. In addition, data on ELS and WM performance were collected in both patients with PSY and healthy controls (HC; n = 41). Resting‐state glutamate concentrations in the bilateral dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) were also assessed with proton magnetic resonance spectroscopy for both PSY and HC groups. t tests, analyses of variance, and regression analyses were utilized. Results Participants with PSY reported significantly more ELS occurrences and showed poorer WM performance than HC. Furthermore, individuals with PSY displayed lower glutamate concentrations in the left DLPFC than HC. Neither ELS nor WM performance were predictive of severity of psychotic symptoms in participants with PSY. However, we found a significant negative correlation between glutamate concentrations in the left DLPFC and ELS occurrence in HC only. Conclusion In individuals with PSY, the current study found no evidence that the association between ELS and psychotic symptoms is mediated by WM performance or prefrontal glutamate concentrations. In HC, the association between ELS experience and glutamate concentrations may indicate a neurometabolite effect of ELS that is independent of an illness effect in psychosis

Neolithic dispersal implications of murids from late Holocene archaeological and modern natural deposits in the Talaud Islands, northern Sulawesi

The Sangihe-Talaud Archipelago represents a group of 77 remote islands located between the Philippines and North Sulawesi, in the northern sector of Wallacea. The Talaud Islands have a rich and significant archaeological record going back to the Pleistocene and are instrumental in understanding Pleistocene colonisation of small islands and later models of Austronesian language dispersal. Here we report on vertebrate material excavated from Leang Mande'et, a late Holocene rockshelter on Karakelang, the main island in the Talaud group. The site represents a periodically occupied shelter used for gardening. Fauna recovered predominately comprises murid elements, with at least four taxa (Rattus rattus, Rattus exulans and two Melomys species) found. The rodents show clear signs of being deposited by raptors rather than humans, unlike the small number of fish remains also recovered. DNA sequences from several Rattus rattus specimens are referrable to Rattus rattus complex lineage IV, a lineage with a southern Indochinese origins and broad modern representation through Indonesia and the Philippines. The lack of any Rattus rattus complex lineage II from Leang Mande’et suggests that the first agricultural inhabitants of this island did not come from Taiwan or northern Indochina, but rather that they either originated from the south or that, once established in the Talauds, opened up significant trade networks to the south and in the process acquired a significant pest

Common ADRB2 Haplotypes Derived from 26 Polymorphic Sites Direct β2-Adrenergic Receptor Expression and Regulation Phenotypes

Background: The β2-adrenergic receptor (β2AR) is expressed on numerous cell-types including airway smooth muscle cells and cardiomyocytes. Drugs (agonists or antagonists) acting at these receptors for treatment of asthma, chronic obstructive pulmonary disease, and heart failure show substantial interindividual variability in response. The ADRB2 gene is polymorphic in noncoding and coding regions, but virtually all ADRB2 association studies have utilized the two common nonsynonymous coding SNPs, often reaching discrepant conclusions. Methodology/Principal Findings: We constructed the 8 common ADRB2 haplotypes derived from 26 polymorphisms in the promoter, 5′UTR, coding, and 3′UTR of the intronless ADRB2 gene. These were cloned into an expression construct lacking a vector-based promoter, so that β2AR expression was driven by its promoter, and steady state expression could be modified by polymorphisms throughout ADRB2 within a haplotype. “Whole-gene” transfections were performed with COS-7 cells and revealed 4 haplotypes with increased cell surface β2AR protein expression compared to the others. Agonist-promoted downregulation of β2AR protein expression was also haplotype-dependent, and was found to be increased for 2 haplotypes. A phylogenetic tree of the haplotypes was derived and annotated by cellular phenotypes, revealing a pattern potentially driven by expression. Conclusions/Significance: Thus for obstructive lung disease, the initial bronchodilator response from intermittent administration of β-agonist may be influenced by certain β2AR haplotypes (expression phenotypes), while other haplotypes may influence tachyphylaxis during the response to chronic therapy (downregulation phenotypes). An ideal clinical outcome of high expression and less downregulation was found for two haplotypes. Haplotypes may also affect heart failure antagonist therapy, where β2AR increase inotropy and are anti-apoptotic. The haplotype-specific expression and regulation phenotypes found in this transfection-based system suggest that the density of genetic information in the form of these haplotypes, or haplotype-clusters with similar phenotypes can potentially provide greater discrimination of phenotype in human disease and pharmacogenomic association studies

Dynamically Driven Evolution of the Interstellar Medium in M51

Massive star formation occurs in giant molecular clouds (GMCs); an understanding of the evolution of GMCs is a prerequisite to develop theories of star formation and galaxy evolution. We report the highest-fidelity observations of the grand-design spiral galaxy M51 in carbon monoxide (CO) emission, revealing the evolution of GMCs vis-a-vis the large-scale galactic structure and dynamics. The most massive GMCs (giant molecular associations (GMAs)) are first assembled and then broken up as the gas flow through the spiral arms. The GMAs and their H_2 molecules are not fully dissociated into atomic gas as predicted in stellar feedback scenarios, but are fragmented into smaller GMCs upon leaving the spiral arms. The remnants of GMAs are detected as the chains of GMCs that emerge from the spiral arms into interarm regions. The kinematic shear within the spiral arms is sufficient to unbind the GMAs against self-gravity. We conclude that the evolution of GMCs is driven by large-scale galactic dynamics—their coagulation into GMAs is due to spiral arm streaming motions upon entering the arms, followed by fragmentation due to shear as they leave the arms on the downstream side. In M51, the majority of the gas remains molecular from arm entry through the interarm region and into the next spiral arm passage

From ocean sprawl to blue-green infrastructure:A UK perspective on an issue of global significance

Artificial structures are proliferating in the marine environment, resulting in ‘ocean sprawl’. In light of the potential environmental impacts of this, such as habitat loss and alteration, it is becoming increasingly important to incorporate ecologically-sensitive design into artificial marine structures. The principles of eco-engineering and green infrastructure are embedded in urban planning practice for terrestrial and freshwater development projects. In marine planning, however, eco-engineering of blue-green infrastructure remains an emerging concept. This note provides a UK perspective on the progress towards uptake of eco-engineering approaches for enhancing biodiversity on artificial marine structures. We emphasise that, despite a clear ‘policy pull’ to incorporate biodiversity enhancements in marine structures, a range of proof-of-concept evidence that it is possible to achieve, and strong cross-sectoral stakeholder support, there are still few examples of truly and purposefullydesigned blue-green artificial structures in the UK. We discuss the barriers that remain and propose a strategy towards effective implementation. Our strategy outlines a step-wise approach to: (1) strengthening the evidence base for what enhancements can be achieved in different scenarios; (2) improving clarity on the predicted benefits and associated costs of enhancements; (3) packaging the evidence in a useful form to support planning and decision-making; and (4) encouraging implementation as routine practice. Given that ocean sprawl is a growing problem globally, the perspective presented here provides valuable insight and lessons for other nations at their various states of progress towards this same goal

Durability and inflammogenic impact of carbon nanotubes compared with asbestos fibres

<p>Abstract</p> <p>Background</p> <p>It has been suggested that carbon nanotubes might conform to the fibre pathogenicity paradigm that explains the toxicities of asbestos and other fibres on a continuum based on length, aspect ratio and biopersistence. Some types of carbon nanotubes satisfy the first two aspects of the fibre paradigm but only recently has their biopersistence begun to be investigated. Biopersistence is complex and requires <it>in vivo </it>testing and analysis. However durability, the chemical mimicking of the process of fibre dissolution using <it>in vitro </it>treatment, is closely related to biopersistence and more readily determined. Here, we describe an experimental process to determine the durability of four types of carbon nanotubes in simulated biological fluid (Gambles solution), and their subsequent pathogenicity <it>in vivo </it>using a mouse model sensitive to inflammogenic effects of fibres. The <it>in vitro </it>and <it>in vivo </it>results were compared with well-characterised glass wool and asbestos fibre controls.</p> <p>Results</p> <p>After incubation for up to 24 weeks in Gambles solution, our control fibres were recovered at percentages consistent with their known <it>in vitro </it>durabilities and/or <it>in vivo </it>persistence, and three out of the four types of carbon nanotubes tested (single-walled (CNT_SW) and multi-walled (CNT_TANG2, CNT_SPIN)) showed no, or minimal, loss of mass or change in fibre length or morphology when examined by electron microscopy. However, the fourth type [multi-walled (CNT_LONG1)] lost 30% of its original mass within the first three weeks of incubation, after which there was no further loss. Electron microscopy of CNT_LONG1samples incubated for 10 weeks confirmed that the proportion of long fibres had decreased compared to samples briefly exposed to the Gambles solution. This loss of mass and fibre shortening was accompanied by a loss of pathogenicity when injected into the peritoneal cavities of C57Bl/6 mice compared to fibres incubated briefly. CNT_SWdid not elicit an inflammogenic effect in the peritoneal cavity assay used here.</p> <p>Conclusions</p> <p>These results support the view that carbon nanotubes are generally durable but may be subject to bio-modification in a sample-specific manner. They also suggest that pristine carbon nanotubes, either individually or in rope-like aggregates of sufficient length and aspect ratio, can induce asbestos-like responses in mice, but that the effect may be mitigated for certain types that are less durable in biological systems. Results indicate that durable carbon nanotubes that are either short or form tightly bundled aggregates with no isolated long fibres are less inflammogenic in fibre-specific assays.</p

Direct spun aligned carbon nanotube web-reinforced proton exchange membranes for fuel cells

A composite membrane prepared by electrospinning SPEEK and direct spinning of CNTs is more robust than SPEEK alone and outperforms SPEEK and Nafion 212 membranes.</p