Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway

<p>Abstract</p> <p>Background</p> <p>To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA).</p> <p>Methods</p> <p>Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents.</p> <p>Results</p> <p>Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p < 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p < 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p < 0.01). Restenosis index (p < 0.01) and intimal hyperplasia (p < 0.01) were significantly reduced while the residual lumen was increased (p < 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels.</p> <p>Conclusions</p> <p>After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia.</p

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

How to increase earthquake and home fire preparedness: the fix-it intervention

Published, evaluated community intervention studies concerning natural hazard preparedness are rare. Most lack a rigorous methodology, thereby hampering the development of evidence-based interventions. This paper describes the rationale and methodology of a cross-cultural, longitudinal intervention study on earthquake and home fire preparedness, termed fix-it. The aim is to evaluate whether and how the intervention brings about behaviour change in the targeted communities in two coastal cities with high seismic risk: Seattle, USA and Izmir, Turkey. Participants are adult residents of these cities. The intervention group attends a 6-h workshop, which focuses on securing items in the household. The control group does not attend the workshop. All participants complete baseline and post-intervention, as well as 3- and 12-month follow-up assessments. The primary outcome measure is an observational measure of nine preparedness items for earthquake and fire in participants’ homes. This is evaluated alongside participants’ self-reports concerning their preparedness levels. Secondary outcomes are changes in levels of self-efficacy, perceived outcome, trust, corruption, empowerment, anxiety and social cohesion. Results from the first of the studies, conducted in Seattle in September 2015, indicate that while the fix-it intervention is effective, in the longer term, multi-hazard preparedness is increased by the mere act of going into people’s homes to observe their preparedness levels along with assessing self-reported preparedness and sociopsychological orientation towards natural hazards. This protocol and study aim to augment the empirical literature on natural hazard preparedness, informing national and international policy on delivery of evidence-based community interventions to promote multi-hazard preparedness in households

A role for a neo-sex chromosome in stickleback speciation.

Sexual antagonism, or conflict between the sexes, has been proposed as a driving force in both sex-chromosome turnover and speciation. Although closely related species often have different sex-chromosome systems, it is unknown whether sex-chromosome turnover contributes to the evolution of reproductive isolation between species. Here we show that a newly evolved sex chromosome contains genes that contribute to speciation in threespine stickleback fish (Gasterosteus aculeatus). We first identified a neo-sex chromosome system found only in one member of a sympatric species pair in Japan. We then performed genetic linkage mapping of male-specific traits important for reproductive isolation between the Japanese species pair. The neo-X chromosome contains loci for male courtship display traits that contribute to behavioural isolation, whereas the ancestral X chromosome contains loci for both behavioural isolation and hybrid male sterility. Our work not only provides strong evidence for a large X-effect on reproductive isolation in a vertebrate system, but also provides direct evidence that a young neo-X chromosome contributes to reproductive isolation between closely related species. Our data indicate that sex-chromosome turnover might have a greater role in speciation than was previously appreciated

The Immature Heart: The Roles of Bone Marrow Stromal Stem Cells in Growth and Myocardial Repair

Studies have shown that adult bone marrow derived stem cells (MSCs) can participate in repair of myocardial injury in adult hearts, as well as in cardiac growth during fetal development in utero. Yet, no studies have evaluated the role of MSCs with respect to normal growth or tissue repair in immature hearts after birth. The present study examines whether MSCs may participate in the myocardial growth and injury in the post-natal immature hearts. MSCs were isolated from adult Lewis rats and labeled with Lac-Z gene using retroviral vectors. These MSCs were injected systemically into groups of neonatal (NB=2days-old), immature (B=30days-old) and adult (A=>3months-old) isogeneic Lewis rats. Additionally, left coronary artery ligation was carried out in subgroups of immature (BL) and adult (AL) rats one week after MSCs injection. The hearts were harvested serially from 2-days to 6-weeks, stained with X-Gal for labeled MSCs. Cardiomyocyte phenotypic expression was evaluated by immunohistological staining for Troponin I-C and Connexin-43. Labeled MSCs were found to home into the bone marrow in all rats of different developmental stages. They could be recruited from bone marrow into the infarcted site of myocardium only in groups AL and BL. They were also capable of differentiating into cardiomyocyte phenotype after myocardial injury. In contrast to that reported in the developing fetus, MSCs did not appear to contribute to the growth of non-injured hearts after birth. However, they can be recruited from the bone marrow and regenerate damaged myocardium both in the adult and in the immature hearts

Sustainable Fictions – Geographical, Literary and Cultural Intersections in J.R.R. Tolkien’s The Lord of the Rings

J. R. R. Tolkien s The Lord of the Rings (1954/1955), one of the founding texts of fantasy literature and the centrepiece of a number of writings about the geography, history and mythology of ‘Middle-earth’, has long become a cult phenomenon. We argue that in this influential text, Tolkien offers a fictional exploration of sustainability. Combining an application of Geographic Information System techniques with textual analysis and interpreting text and spatial data in conjunction, we show that there is a systematically varying distance between our real world and the physical features of Tolkien's ‘Secondary World’, as regards climate and vegetation patterns. There is an emphasis on land degeneration, a ‘missing forest problem’ which prompts a closer look at the role of woods and trees in Tolkien's work. It emerges that the preservation of trees is at the centre of Tolkien's sustainable fictions. For the author, it was a function of fantasy, which he sets against a dystopian and secular modernism as well as the destructive aspects of modernity, to provide (positive) ‘escape’, ‘consolation’ and ‘recovery’, which is achieved through a final vision of the successful preservation of the environment