Sphingosine-1-phosphate–induced smooth muscle cell migration involves the mammalian target of rapamycin

BackgroundVascular smooth muscle cell (SMC) migration is an important component of the development of intimal hyperplasia. Sphingosine-1-phosphate (S-1-P) is a lipid released from activated platelets with numerous cellular effects including the stimulation of SMC migration in vitro. We examined the role of the mammalian target of rapamycin and ribosomal p70S6 kinase (p70S6K) in S-1-P–induced SMC migration.MethodsRat arterial SMCs were cultured in vitro. Linear wound and Boyden microchemotaxis assays of migration were performed in the presence of S-1-P (0.01 to 100 μmol/L) with and without rapamycin (10 nmol/L). Western blotting was performed for phosphorylated and total p70S6K, ERK1/2, and p38MAPK after stimulation with S-1-P (0.1 μmol/L), with and without rapamycin pretreatment. Phosphorylation of p70S6K was also assayed after S-1-P treatment in the presence and absence of inhibitors of PI3 kinase (wortmannin, WN, and LY294002, LY), Akt (AktI), p38MAPK (SB203580), and MEK1 (PD98059).ResultsS-1-P stimulated migration of SMCs in both linear wound and Boyden chamber assays compared to control (P < .05); these responses were inhibited by rapamycin to below the level of control (P < .05 vs S-1-P alone for both assays) in a dose-dependent manner (inhibitory concentration of 50%, 10 nmol/L). S-1-P stimulated phosphorylation of ERK1/2, p38MAPK, and p70S6K, which peaked at 5 minutes for ERK1/2 and p38MAPK and10 minutes for p70S6K (2-fold increase over control for each, P < .05). Rapamycin prevented the phosphorylation of p70S6K at the Thr 389 site (which correlates with enzyme activity), reduced ERK1/2 phosphorylation, but had no effect on the Thr 421/Ser 424 site or on p38MAPK phosphorylation. Wortmannin and LY294002 inhibited phosphorylation of the Thr 389 site of p70S6K. AktI and SB203580 had no effect on p70S6K, whereas PD98059 had a marginal effect.ConclusionsS-1-P–induced SMC migration was completely inhibited by rapamycin, indicating that the p70S6K pathway is involved. This mechanism likely involves modulation of the ERK1/2 pathway. S-1-P stimulates phosphorylation of p70S6K in a MEK1-dependent, PI3 kinase–dependent, but Akt-independent manner.Clinical relevanceS-1-P is released from activated platelets at sites of vessel injury and contributes to the development of intimal hyperplasia after bypass grafting, angioplasty, and stenting. S-1-P is a potent pro-migratory molecule for SMCs. Rapamycin is a commonly used immunosuppressive agent that has most recently been incorporated as the biologic agent in drug eluting stents with good success in the coronary circulation. Rapamycin inhibits the mammalian target of rapamycin, which, in turn, controls the translational mechanisms of the cell. The role of translational control during S-1-P–induced SMC migration is poorly understood. This study identifies a link between the mammalian target of rapamycin translational pathway and S-1-P and demonstrates how rapamycin might interfere with another facet of a vessel's response to injury after a vascular intervention, namely by interfering with the cell signaling of factors released from platelets deposited at the injury site

Acoustically driven storage of light in a quantum well

The strong piezoelectric fields accompanying a surface acoustic wave on a semiconductor quantum well structure are employed to dissociate optically generated excitons and efficiently trap the created electron hole pairs in the moving lateral potential superlattice of the sound wave. The resulting spatial separation of the photogenerated ambipolar charges leads to an increase of the radiative lifetime by orders of magnitude as compared to the unperturbed excitons. External and deliberate screening of the lateral piezoelectric fields triggers radiative recombination after very long storage times at a remote location on the sample.Comment: 4 PostScript figures included, Physical Review Letters, in pres

Rapid retreat of permafrost coastline observed with aerial drone photogrammetry

Permafrost landscapes are changing around the Arctic in response to climate warming, with coastal erosion being one of the most prominent and hazardous features. Using drone platforms, satellite images, and historic aerial photographs, we observed the rapid retreat of a permafrost coastline on Qikiqtaruk – Herschel Island, Yukon Territory, in the Canadian Beaufort Sea. This coastline is adjacent to a gravel spit accommodating several culturally significant sites and is the logistical base for the Qikiqtaruk – Herschel Island Territorial Park operations. In this study we sought to (i) assess short-term coastal erosion dynamics over fine temporal resolution, (ii) evaluate short-term shoreline change in the context of long-term observations, and (iii) demonstrate the potential of low-cost lightweight unmanned aerial vehicles (“drones”) to inform coastline studies and management decisions. We resurveyed a 500&thinsp;m permafrost coastal reach at high temporal frequency (seven surveys over 40&thinsp;d in 2017). Intra-seasonal shoreline changes were related to meteorological and oceanographic variables to understand controls on intra-seasonal erosion patterns. To put our short-term observations into historical context, we combined our analysis of shoreline positions in 2016 and 2017 with historical observations from 1952, 1970, 2000, and 2011. In just the summer of 2017, we observed coastal retreat of 14.5&thinsp;m, more than 6 times faster than the long-term average rate of 2.2±0.1&thinsp;m&thinsp;a−1 (1952–2017). Coastline retreat rates exceeded 1.0±0.1&thinsp;m&thinsp;d−1 over a single 4&thinsp;d period. Over 40&thinsp;d, we estimated removal of ca. 0.96&thinsp;m3&thinsp;m−1&thinsp;d−1. These findings highlight the episodic nature of shoreline change and the important role of storm events, which are poorly understood along permafrost coastlines. We found drone surveys combined with image-based modelling yield fine spatial resolution and accurately geolocated observations that are highly suitable to observe intra-seasonal erosion dynamics in rapidly changing Arctic landscapes.</p

Triamidoamine-supported zirconium: Hydrogen activation, Lewis acidity, and: Rac -lactide polymerization

Investigation of a triamidoamine-supported zirconium hydride intermediate, important to a range of catalytic reactions, revealed the potential Lewis acidity of [κ5-N,N,N,N,C-(Me3SiNCH2CH2)2NCH2CH2NSiMe2CH2]Zr (1). A preliminary study of 1 as a precursor for the polymerization of rac-lactide showed modest activity but indicated that five-coordinate zirconium complexes with tetra-N donor ligands may be an avenue for further development in group 4 metal lactide polymerization catalysis

Nonlinear acousto-electric transport in a two-dimensional electron system

We study both theoretically and experimentally the nonlinear interaction between an intense surface acoustic wave and a two-dimensional electron plasma in semiconductor-piezocrystal hybrid structures. The experiments on hybrid systems exhibit strongly nonlinear acousto-electric effects. The plasma turns into moving electron stripes, the acousto-electric current reaches its maximum, and the sound absorption strongly decreases. To describe the nonlinear phenomena, we develop a coupled-amplitude method for a two-dimensional system in the strongly nonlinear regime of interaction. At low electron densities the absorption coefficient decreases with increasing sound intensity, whereas at high electron density the absorption coefficient is not a monotonous function of the sound intensity. High-harmonic generation coefficients as a function of the sound intensity have a nontrivial behavior. Theory and experiment are found to be in a good agreement.Comment: 27 pages, 6 figure

Crystallographic Education in the 21st Century

There are many methods that can be used to incorporate concepts of crystallography into the learning experiences of students, whether they are in elementary school, at university or part of the public at large. It is not always critical that those who teach crystallography have immediate access to diffraction equipment to be able to introduce the concepts of symmetry, packing or molecular structure in an age- and audience-appropriate manner. Crystallography can be used as a tool for teaching general chemistry concepts as well as general research techniques without ever having a student determine a crystal structure. Thus, methods for younger students to perform crystal growth experiments of simple inorganic salts, organic compounds and even metals are presented. For settings where crystallographic instrumentation is accessible (proximally or remotely), students can be involved in all steps of the process, from crystal growth, to data collection, through structure solution and refinement, to final publication. Several approaches based on the presentations in the MS92 Microsymposium at the IUCr 23rd Congress and General Assembly are reported. The topics cover methods for introducing crystallography to undergraduate students as part of a core chemistry curriculum; a successful short-course workshop intended to bootstrap researchers who rely on crystallography for their work; and efforts to bring crystallography to secondary school children and non-science majors. In addition to these workshops, demonstrations and long-format courses, open-format crystallographic databases and three-dimensional printed models as tools that can be used to excite target audiences and inspire them to pursue a deeper understanding of crystallography are described

State and local governments plan for development of most land vulnerable to rising sea level along the US Atlantic coast

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of IOP Publishing for personal use, not for redistribution. The definitive version was published in Environmental Research Letters 4 (2009): 044008, doi:10.1088/1748-9326/4/4/044008.Rising sea level threatens existing coastal wetlands. Overall ecosystems could often survive by migrating inland, if adjacent lands remained vacant. On the basis of 131 state and local land use plans, we estimate that almost 60% of the land below 1 m along the US Atlantic coast is expected to be developed and thus unavailable for the inland migration of wetlands. Less than 10% of the land below 1 m has been set aside for conservation. Environmental regulators routinely grant permits for shore protection structures (which block wetland migration) on the basis of a federal finding that these structures have no cumulative environmental impact. Our results suggest that shore protection does have a cumulative impact. If sea level rise is taken into account, wetland policies that previously seemed to comply with federal law probably violate the Clean Water Act

Electroosmotically generated disinfectant from urine as a by-product of electricity in microbial fuel cell for the inactivation of pathogenic species

This work presents a small scale and low cost ceramic based microbial fuel cell, utilising human urine into electricity, while producing clean catholyte into an initially empty cathode chamber through the process of electro-osmostic drag. It is the first time that the catholyte obtained as a by-product of electricity generation from urine was transparent in colour and reached pH>13 with high ionic conductivity values. The catholyte was collected and used ex situ as a killing agent for the inactivation of a pathogenic species such as Salmonella typhimurium, using a luminometer assay. Results showed that the catholyte solutions were efficacious in the inactivation of the pathogen organism even when diluted up to 1:10, resulting in more than 5 log-fold reduction in 4 min. Long-term impact of the catholyte on the pathogen killing was evaluated by plating Salmonella typhimurium on agar plates and showed that the catholyte possesses a long-term killing efficacy and continued to inhibit pathogen growth for 10 days

Is there an association between seeing incidents of alcohol or drug use in films and young Scottish adults' own alcohol or drug use? A cross sectional study

&lt;p&gt;Background: As the promotion of alcohol and tobacco to young people through direct advertising has become increasingly restricted, there has been greater interest in whether images of certain behaviours in films are associated with uptake of those behaviours in young people. Associations have been reported between exposure to smoking images in films and smoking initiation, and between exposure to film alcohol images and initiation of alcohol consumption, in younger adolescents in the USA and Germany. To date no studies have reported on film images of recreational drug use and young people's own drug use.&lt;/p&gt; &lt;p&gt;Methods: Cross sectional multivariable logistic regression analysis of data collected at age 19 (2002-4) from a cohort of young people (502 boys, 500 girls) previously surveyed at ages 11 (in 1994-5), 13 and 15 in schools in the West of Scotland. Outcome measures at age 19 were: exceeding the 'sensible drinking' guidelines ('heavy drinkers') and binge drinking (based on alcohol consumption reported in last week), and ever use of cannabis and of 'hard' drugs. The principle predictor variables were an estimate of exposure to images of alcohol, and of drug use, in films, controlling for factors related to the uptake of substance use in young people.&lt;/p&gt; &lt;p&gt;Results: A third of these young adults (33%) were classed as 'heavy drinkers' and half (47%) as 'binge drinkers' on the basis of their previous week's consumption. Over half (56%) reported ever use of cannabis and 13% ever use of one or more of the 'hard' drugs listed. There were linear trends in the percentage of heavy drinkers (p = .018) and binge drinkers (p = 0.012) by film alcohol exposure quartiles, and for ever use of cannabis by film drug exposure (p = .000), and for ever use of 'hard' drugs (p = .033). The odds ratios for heavy drinking (1.56, 95% CI 1.06-2.29 comparing highest with lowest quartile of film alcohol exposure) and binge drinking (1.59, 95% CI 1.10-2.30) were attenuated by adjustment for gender, social class, family background (parental structure, parental care and parental control), attitudes to risk-taking and rule-breaking, and qualifications (OR heavy drinking 1.42, 95% CI 0.95-2.13 and binge drinking 1.49, 95% CI 1.01-2.19), and further so when adjusting for friends' drinking status (when the odds ratios were no longer significant). A similar pattern was seen for ever use of cannabis and 'hard' drugs (unadjusted OR 1.80, 95% CI 1.24-2.62 and 1.57, 95% CI 0.91-2.69 respectively, 'fully' adjusted OR 1.41 (0.90-2.22 and 1.28 (0.66-2.47) respectively).&lt;/p&gt; &lt;p&gt;Conclusions: Despite some limitations, which are discussed, these cross-sectional results add to a body of work which suggests that it is important to design good longitudinal studies which can determine whether exposure to images of potentially health-damaging behaviours lead to uptake of these behaviours during adolescence and early adulthood, and to examine factors that might mediate this relationship.&lt;/p&gt

Disturbed Expression of Splicing Factors in Renal Cancer Affects Alternative Splicing of Apoptosis Regulators, Oncogenes, and Tumor Suppressors

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. One of the processes disturbed in this cancer type is alternative splicing, although phenomena underlying these disturbances remain unknown. Alternative splicing consists of selective removal of introns and joining of residual exons of the primary transcript, to produce mRNA molecules of different sequence. Splicing aberrations may lead to tumoral transformation due to synthesis of impaired splice variants with oncogenic potential. In this paper we hypothesized that disturbed alternative splicing in ccRCC may result from improper expression of splicing factors, mediators of splicing reactions. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time PCR and Western-blot analysis we analyzed expression of seven splicing factors belonging to SR proteins family (SF2/ASF, SC35, SRp20, SRp75, SRp40, SRp55 and 9G8), and one non-SR factor, hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1) in 38 pairs of tumor-control ccRCC samples. Moreover, we analyzed splicing patterns of five genes involved in carcinogenesis and partially regulated by analyzed splicing factors: RON, CEACAM1, Rac1, Caspase-9, and GLI1. CONCLUSIONS/SIGNIFICANCE: We found that the mRNA expression of splicing factors was disturbed in tumors when compared to paired controls, similarly as levels of SF2/ASF and hnRNP A1 proteins. The correlation coefficients between expression levels of specific splicing factors were increased in tumor samples. Moreover, alternative splicing of five analyzed genes was also disturbed in ccRCC samples and splicing pattern of two of them, Caspase-9 and CEACAM1 correlated with expression of SF2/ASF in tumors. We conclude that disturbed expression of splicing factors in ccRCC may possibly lead to impaired alternative splicing of genes regulating tumor growth and this way contribute to the process of carcinogenesis