Engineering of fibrin-based functional and implantable small-diameter blood vessels

We engineered implantable small-diameter blood vessels based on ovine smooth muscle and endothelial cells embedded in fibrin gels. Cylindrical tissue constructs remodeled the fibrin matrix and exhibited considerable reactivity in response to receptor- and nonreceptor-mediated vasoconstrictors and dilators. Aprotinin, a protease inhibitor of fibrinolysis, was added at varying concentrations and affected the development and functionality of tissue-engineered blood vessels (TEVs) in a concentration-dependent manner. Interestingly, at moderate concentrations, aprotinin increased mechanical strength but decreased vascular reactivity, indicating a possible relationship between matrix degradation/remodeling, vasoreactivity, and mechanical properties. TEVs developed considerable mechanical strength to withstand interpositional implantation in jugular veins of lambs. Implanted TEVs integrated well with the native vessel and demonstrated patency and similar blood flow rates as the native vessels. At 15 wk postimplantation, TEVs exhibited remarkable matrix remodeling with production of collagen and elastin fibers and orientation of smooth muscle cells perpendicular to the direction of blood flow. Implanted vessels gained significant mechanical strength and reactivity that were comparable to those of native veins. Our work demonstrates that fibrin-based TEVs hold significant promise for treatment of vascular disease and as a biological model for studying vascular development and pathophysiology.     

Curriculum for education and training of Medical Physicists in Nuclear Medicine: Recommendations from the EANM Physics Committee,the EANM Dosimetry Committee and EFOMP

PurposeTo provide a guideline curriculum covering theoretical and practical aspects of education and training for Medical Physicists in Nuclear Medicine within Europe.Material and methodsNational training programmes of Medical Physics, Radiation Physics and Nuclear Medicine physics from a range of European countries and from North America were reviewed and elements of best practice identified. An independent panel of experts was used to achieve consensus regarding the content of the curriculum.ResultsGuidelines have been developed for the specialist theoretical knowledge and practical experience required to practice as a Medical Physicist in Nuclear Medicine in Europe. It is assumed that the precondition for the beginning of the training is a good initial degree in Medical Physics at master level (or equivalent). The Learning Outcomes are categorised using the Knowledge, Skill and Competence approach along the lines recommended by the European Qualifications Framework. The minimum level expected in each topic in the theoretical knowledge and practical experience sections is intended to bring trainees up to the requirements expected of a Medical Physicist entering the field of Nuclear Medicine.ConclusionsThis new joint EANM/EFOMP European guideline curriculum is a further step to harmonise specialist training of Medical Physicists in Nuclear Medicine within Europe. It provides a common framework for national Medical Physics societies to develop or benchmark their own curricula. The responsibility for the implementation and accreditation of these standards and guidelines resides within national training and regulatory bodies.     

Intermediate filaments in cardiomyopathy

Intermediate filament (IF) proteins are critical regulators in health and disease. The discovery of hundreds of mutations in IF genes and posttranslational modifications has been linked to a plethora of human diseases, including, among others, cardiomyopathies, muscular dystrophies, progeria, blistering diseases of the epidermis, and neurodegenerative diseases. The major IF proteins that have been linked to cardiomyopathies and heart failure are the muscle-specific cytoskeletal IF protein desmin and the nuclear IF protein lamin, as a subgroup of the known desminopathies and laminopathies, respectively. The studies so far, both with healthy and diseased heart, have demonstrated the importance of these IF protein networks in intracellular and intercellular integration of structure and function, mechanotransduction and gene activation, cardiomyocyte differentiation and survival, mitochondrial homeostasis, and regulation of metabolism. The high coordination of all these processes is obviously of great importance for the maintenance of proper, life-lasting, and continuous contraction of this highly organized cardiac striated muscle and consequently a healthy heart. In this review, we will cover most known information on the role of IFs in the above processes and how their deficiency or disruption leads to cardiomyopathy and heart failure.     

Anthropogenic disturbance of coastal habitats promotes the spread of the introduced scleractinian coral Oculina patagonica in the Mediterranean Sea

The extensive human-mediated modifications of shallow coastal habitats drastically alter selection regimes and may assist alien invasions. The preferential presence of a non-indigenous scleractinian coral (Oculina patagonica) on anthropogenic hard substrata was investigated in a highly disturbed coastal area, along the eastern Saronikos Gulf (Aegean Sea, Eastern Mediterranean). Although the species occurred on both natural and anthropogenic substrata at similar frequencies, its abundance was substantially higher on the latter. The species was present all along the shallow (0.5–5 m) infralittoral zone of the studied coastline, and its percent cover even exceeded 50 % at a site of anthropogenic hard substratum. The occupancy of the species declined with distance from a highly disturbed industrialized/urbanized area (Athens metropolitan coastal front and the port of Piraeus). Space availability as a result of habitat modification appears to have been an important factor enhancing the coral’s abundance in this area. The ongoing degradation of the coastal zone, as a combined effect of coastal pollution, proliferation of artificial substrata and overgrazing seems to be paving the way to this new invasion in the Aegean Sea.     

Regulation of Ang2 release by PTEN/PI3-kinase/Akt in lung microvascular endothelial cells

Angiopoietin-2 (Ang2) is a Tie-2 ligand that destabilizes vascular structures, allowing for neovascularization or vessel regression depending on local vascular endothelial cell growth factor (VEGF) concentrations. Although various stimuli have been shown to affect Ang2 expression, information on the underlying mechanisms involved in Ang2 production in endothelial cells (EC) is just beginning to emerge. In the present study, we have used adenovirus-mediated gene transfer and pharmacological inhibitors to examine the role of the PTEN/PI3-K/Akt pathway on Ang2 release. Inhibition of PI3-kinase with wortmannin led to a stimulation of basal Ang2 release in EC, while overexpression of an active form of Akt reduced Ang2. In addition, adenovirus-mediated gene transfer of the phosphatase PTEN stimulated Ang2 release. Incubation of the cells with Ang1, an agent that activates the PI3-K/Akt pathway in EC, reduced Ang2 release. This effect of Ang1 could be prevented by wortmannin and LY-294002 pretreatment. Similarly, in VEGF-treated EC the increase in Ang2 production observed was greater in the presence of a PI3-K inhibitor. Our observations that PTEN acts as a positive modulator of Ang2 release, while activation of the PI3-K/Akt pathway downregulates Ang2, reveal an additional mechanism through which the PTEN/PI3-K/Akt pathway could affect the angiogenic process.     

Improved Performance and Reliability of p‐i‐n Perovskite Solar Cells via Doped Metal Oxides

Perovskite photovoltaics (PVs) have attracted attention because of their excellent power conversion efficiency (PCE). Critical issues related to large‐area PV performance, reliability, and lifetime need to be addressed. Here, it is shown that doped metal oxides can provide ideal electron selectivity, improved reliability, and stability for perovskite PVs. This study reports p‐i‐n perovskite PVs with device areas ranging from 0.09 cm² to 0.5 cm² incorporating a thick aluminum‐doped zinc oxide (AZO) electron selective contact with hysteresis‐free PCE of over 13% and high fill factor values in the range of 80%. AZO provides suitable energy levels for carrier selectivity, neutralizes the presence of pinholes, and provides intimate interfaces. Devices using AZO exhibit an average PCE increase of over 20% compared with the devices without AZO and maintain the high PCE for the larger area devices reported. Furthermore, the device stability of p‐i‐n perovskite solar cells under the ISOS‐D‐1 is enhanced when AZO is used, and maintains 100% of the initial PCE for over 1000 h of exposure when AZO/Au is used as the top electrode. The results indicate the importance of doped metal oxides as carrier selective contacts to achieve reliable and high‐performance long‐lived large‐area perovskite solar cells.     

Estimation of roe deerCapreolus capreolus and mouflonOvis aries densities, abundance and habitat use in a mountainous Mediterranean area

The abundance, density, and habitat use of roe deerCapreolus capreolus (Linnaeus, 1758) and mouflonOvis aries Linnaeus, 1758 were studied in a confined Mediterranean area in Greece with a dung survey based on the faecal accumulation rate (FAR) technique. Estimated density was modelled with generalized additive models using altitude, habitat type, and slope as potential covariates. Model selection among the set of candidate models was conducted based on their generalized cross-validation score. Roe deer had an estimated mean density of 13.9 ind./km² and the best model included slope and habitat type as covariates. The mean density of mouflon in the study area was 22.1 ind./km² and the best model used altitude and habitat type as covariates. For both species, the highest densities were encountered in abandoned cultivations and glades, followed by conifer forests, while the lowest densities were observed in maquis. However, use of open habitats by mouflon was much greater than it was for roe deer. The strong preference of mouflon (a grazer species) for open habitats that were abundant with grasses probably reflected food availability and contrasted with the more diverse habitat use by roe deer (a selective browser).     

Differences in circular dichroism and fluorescence between the DNA complexes formed with 3-amino- and 3,8- diaminophenanthridinium derivatives

The conformation of DNA complexes formed with various 3-amino- and 3,8-diamino-phenanthridinium derivatives were examined by CD and fluorescence methods. The CD of these complexes is characterized by major bands in the 300–350-nm and the 400–550-nm regions. The CD properties of the complexes formed with diaminophenanthridinium derivatives suggest that the structure of such complexes is well represented by the intercalation complex formed between DNA and ethidium bromide. The substantial and regular increases in ellipticities near 308 nm that occur with increasing DNA-bound diaminophenanthridinium to DNA phosphate ratios (r) may result from direct interactions between molecules intercalated in neighbouring binding sites. In contrast, the changes in the shape of the CD of DNA complexes of monoaminophenanthridinium derivatives with r and the much lower maximum ellipticities attained suggest that near-neighbor interactions among intercalated monoaminophenanthridinium derivatives occur much less efficiently than in the corresponding diamino complexes, if at all. Although alternative explanations for the differences in the optical properties between the mono- and diaminophenanthridinium complexes of DNA may be offered, such results seem to indicate that complexes formed with monoaminophenanthridinium derivatives are characterized by a conformation which is quite distinct and different from that of the DNA–diaminophenanthridinium complexes. This conclusion is further supported by the considerable increase in fluorescence that accompanies the binding of the diaminophenanthridinium derivatives to DNA as compared to the minor increases, which occur upon the binding of the monoaminophenanthridinium compounds. The importance of conformation as a factor influencing template, function, especially with respect to the RNA polymerase-catalyzed synthesis of RNA, is now well appreciated. Therefore, methods which could provide information readily about changes in the conformation of a template, i.e., as a result of dye intercalation, are expected to facilitate our understanding of the effects of conformational change on the function and activity of templates.