Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells

Extracellular vesicles (EVs) represent a promising cell-free alternative for treatment of cardiovascular diseases. Nevertheless, the lack of standardised and reproducible isolation methods capable of recovering pure, intact EVs presents a significant obstacle. Additionally, there is significant interest in investigating the interactions of EVs with different cardiac cell types. Here we established a robust technique for the production and isolation of EVs harvested from an enriched (>97% purity) population of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) with size exclusion chromatography. Utilizing an advanced fluorescence labelling strategy, we then investigated the interplay of the CM-EVs with the three major cellular components of the myocardium (fibroblasts, cardiomyocytes and endothelial cells) and identified that cardiac endothelial cells show preferential uptake of these EVs. Overall, our findings provide a great opportunity to overcome the translational hurdles associated with the isolation of intact, non-aggregated human iPSC-CM EVs at high purity. Furthermore, understanding in detail the interaction of the secreted EVs with their surrounding cells in the heart may open promising new avenues in the field of EV engineering for targeted delivery in cardiac regeneration

Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells

Extracellular vesicles (EVs) represent a promising cell-free alternative for treatment of cardiovascular diseases. Nevertheless, the lack of standardised and reproducible isolation methods capable of recovering pure, intact EVs presents a significant obstacle. Additionally, there is significant interest in investigating the interactions of EVs with different cardiac cell types. Here we established a robust technique for the production and isolation of EVs harvested from an enriched (>97% purity) population of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) with size exclusion chromatography. Utilizing an advanced fluorescence labelling strategy, we then investigated the interplay of the CM-EVs with the three major cellular components of the myocardium (fibroblasts, cardiomyocytes and endothelial cells) and identified that cardiac endothelial cells show preferential uptake of these EVs. Overall, our findings provide a great opportunity to overcome the translational hurdles associated with the isolation of intact, non-aggregated human iPSC-CM EVs at high purity. Furthermore, understanding in detail the interaction of the secreted EVs with their surrounding cells in the heart may open promising new avenues in the field of EV engineering for targeted delivery in cardiac regeneration

Learning democracy in social work

In this contribution, we discuss the role of social work in processes of democracy. A key question in this discussion concerns the meaning of ‘the social’ in social work. This question has often been answered in a self-referential way, referring to a methodological identity of social work. This defines the educational role of social work as socialisation (be it socialisation into obedience or into an empowered citizen). However, the idea of democracy as ‘ongoing experiment’ and ‘beyond order’ challenges this methodological identity of social work. From the perspective of democracy as an ‘ongoing experiment’, the social is to be regarded as a platform for dissensus, for ongoing discussions on the relation between private and public issues in the light of human rights and social justice. Hence, the identity of social work cannot be defined in a methodological way; social work is a complex of (institutionalized) welfare practices, to be studied on their underlying views on the ‘social’ as a political and educational concept, and on the way they influence the situation of children, young people and adults in society

Gender specific factors associated with having stopped smoking among in-school adolescents in Ukraine: results from the Global Youth Tobacco Survey 2005

<p>Abstract</p> <p>Background</p> <p>The prevalence of cigarette smoking in Ukraine is different between genders and is among the highest in the world. There is need to identify gender-specific factors that are associated with having stopped smoking among adolescents.</p> <p>Findings</p> <p>We used data from the Ukraine Global Youth Tobacco Survey 2005. We carried out a backward stepwise logistic regression analysis with having stopped smoking as the outcome.</p> <p>Altogether, 2800 adolescents reported having ever smoked cigarettes. Overall 64.1% (63.4% male, and 65.5% female) adolescents reported having stopped smoking. Male adolescents who stated that smoking decreases body weight were 25% more likely, while female adolescents were 9% less likely to stop smoking. While male adolescents who received support on how to stop smoking from a family member were 7% less likely, female adolescents were 60% more likely to stop smoking. Furthermore, while male adolescents who received a lecture on the harmful effects of smoking were 10% less likely, female adolescents were 9% more likely to stop smoking. Finally both male and female adolescents who were sure or most probably that they would not smoke a cigarette offered to them by their best friends were more likely, and those adolescents who were sure that smoking is harmful to health were less likely to stop smoking.</p> <p>Conclusions</p> <p>Our study has identified some factors that are associated with having quit smoking that are gender-specific. We believe public health programs targeting adolescent smoking should consider these factors in their design and implementation of gender sensitive interventions.</p

Constitutive basal and stimulated human small bowel contractility is enhanced in obesity

Small bowel contractility may be more prominent in obese subjects, such that there is enhanced nutrient absorption and hunger stimulation. However, there is little evidence to support this. This study examined in vitro small bowel contractility in obese patients versus non-obese patients

Interleaved Parton Showers and Tuning Prospects

General-purpose Monte Carlo event generators have become important tools in particle physics, allowing the simulation of exclusive hadronic final states. In this article we examine the Pythia 8 generator, in particular focusing on its parton-shower algorithms. Some relevant new additions to the code are introduced, that should allow for a better description of data. We also implement and compare with 2 to 3 real-emission QCD matrix elements, to check how well the shower algorithm fills the phase space away from the soft and collinear regions. A tuning of the generator to Tevatron data is performed for two PDF sets and the impact of first new LHC data is examined

Massive stars as thermonuclear reactors and their explosions following core collapse

Nuclear reactions transform atomic nuclei inside stars. This is the process of stellar nucleosynthesis. The basic concepts of determining nuclear reaction rates inside stars are reviewed. How stars manage to burn their fuel so slowly most of the time are also considered. Stellar thermonuclear reactions involving protons in hydrostatic burning are discussed first. Then I discuss triple alpha reactions in the helium burning stage. Carbon and oxygen survive in red giant stars because of the nuclear structure of oxygen and neon. Further nuclear burning of carbon, neon, oxygen and silicon in quiescent conditions are discussed next. In the subsequent core-collapse phase, neutronization due to electron capture from the top of the Fermi sea in a degenerate core takes place. The expected signal of neutrinos from a nearby supernova is calculated. The supernova often explodes inside a dense circumstellar medium, which is established due to the progenitor star losing its outermost envelope in a stellar wind or mass transfer in a binary system. The nature of the circumstellar medium and the ejecta of the supernova and their dynamics are revealed by observations in the optical, IR, radio, and X-ray bands, and I discuss some of these observations and their interpretations.Comment: To be published in " Principles and Perspectives in Cosmochemistry" Lecture Notes on Kodai School on Synthesis of Elements in Stars; ed. by Aruna Goswami & Eswar Reddy, Springer Verlag, 2009. Contains 21 figure