Label-Free 3D Imaging of Development of Cell Patterns in Drosophila melanogaster Wing Imaginal Disc

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7-August 11, 201

20. Setting the pace for strengthening radiotherapy in Europe: the estro esquire project

In most medical specialties the success rate and outcome of treatment coincide and can be measured immediately. This is not the case for radiotherapy where debilitating of even lethal side effects may show up as late as 18 years after treatment. To determine the outcome or therapeutic ratio of radiotherapy, it is therefore necessary to link tumour control closely to the actuarial long-term disease free survival of the patient.The therapeutic window for radiotherapy is narrow. In walking the tightrope between cure and complications, radiotherapy can put the odds at its side. As a precautionary measure, strict quality assurance measures including the monitoring of side effects need to be put in place. Recent studies have demonstrated that every gain in the accuracy of the beam output and treatment delivery is translated into important gains in the uncomplicated cure probability, thus sparing the lives of thousands of patients every year. QA will become all the more mandatory now that new technological developments allow much more precision in the delivery of the intended dose to the intended target volume, thus making an escalation of the dose and hence the improvement of the cancer cure rata possible.Europe has only half the number of treatment units of America and Japan. However, it has also its own strengths. These are exactly in the field of quality assurance and education. ESTRO has become a world leader in the provision of teaching in the field of radiotherapy. The ESTRO teaching programme commands the admiration and even the envy of the International radiation oncology community. We need to capitalise on this achievement and keep it at the cutting edge of scientific and technological progress to offset, through the development of the human potential and optima) use of capital-intensive infrastructural resources, at least partially the shortage in capital investment and the past shortfall in spending for research.For this reason ESTRO is embarking on an ambitious new project called ESQUIRE (Education, Science and Quality Assurance In Radiotherapy in Europe) which it hopes to realise with the support of EU funding. The aim of this project is to increase the confidence level of clinicians for embracing optimised RT treatment regimes by making sure they can be introduced without an increase in severe side effects. Actions proposed for this purpose: monitoring the accuracy of the dose (Talk 1:E∼UAL) and the side effects (Task 2: REACT), by stepping up education for the implementation of new technology (Task 3: EDRO,) by developing quality assurance procedures for optimised RT (Task 5: QUASIMODO) and brachytherapy (Task 6: BRAPHY∼S), and establishing a procedure-based surveillance of quality in treatment and research (Task 4:EPOQART)

The pro-neurotrophin receptor sortilin is a major neuronal apolipoprotein E receptor for catabolism of amyloid-β peptide in the brain

Apolipoprotein E (APOE) is the major risk factor for sporadic Alzheimer's disease. Among other functions, APOE is proposed to sequester neurotoxic amyloid-{beta} (A{beta}) peptides in the brain, delivering them to cellular catabolism via neuronal APOE receptors. Still, the receptors involved in this process remain controversial. Here, we identified the pro-neurotrophin receptor sortilin as major endocytic pathway for clearance of APOE/A{beata} complexes in neurons. Sortilin binds APOE with high affinity. Lack of receptor expression in mice results in accumulation of APOE and of A{beta} in the brain and in aggravated plaque burden. Also, primary neurons lacking sortilin exhibit significantly impaired uptake of APOE/A{beta} complexes despite proper expression of other APOE receptors. Despite higher than normal brain APOE levels, sortilin-deficient animals display anomalies in brain lipid metabolism (e.g., accumulation of sulfatides) seen in APOE-deficient mice, indicating functional deficiency in cellular APOE uptake pathways. Together, our findings identified sortilin as an essential neuronal pathway for APOE-containing lipoproteins in vivo and suggest an intriguing link between A{beta} catabolism and pro-neurotrophin signaling converging on this receptor

Разработка и применение современных лабораторных методов в эпидемиологическом мониторинге, диагностики и лечении энтеровирусных инфекций

У роботі проведена порівняльна оцінка специфічності й чутливості тест-системи ПЛР, зі специфічним праймером до ДНК 207 п.н. 5'-нетрансльованої області генома энтеровируса для всіх типів ентеровірусів (крім вірусу поліомієліту) у порівнянні із класичним культуральним методом. А також методологічний підхід спільного використання вищеописаної реакції ПЦР із визначенням антитіл класу Іg до вірусів Коксаки й ЕСНО у системі ІФА діагностики, розробленої авторами, і спектр застосування розробленого комплекс.In work the estimation of specificity and sensitivity of test system PTSR, with specific primers to DNA 207 n.n is spent comparative. 5 '-not broadcast areas генома an enterovirus for all types of enteroviruses (except a poliomyelitis virus) in comparison with classical the virology a method. And also the methodological approach of sharing of above described reaction PCR with definition of antibodies of a class ІgG to viruses Cocsaki and ЕСНО in system IFA of diagnostics developed by authors, and a spectrum of application of the developed complex

Investigating migration and mobility in the Early Roman frontier: The case of the Batavi in the Dutch Rhine delta (c. 50/30 BC–AD 40)

The study of migration is essential for understanding the earliest phases of the Roman period in the Lower Rhine delta. This paper applies an integrated and interdisciplinary approach, combining and comparing historical, archaeological and science-based evidence and methodologies, allowing a more detailed reconstruction of immigration during this period. Our study suggests that various groups migrated to our region, probably over a longer period of time, originating from different regions and arriving in a land with a (probably limited) residual population. This marked and varied immigration should be understood in the context of Roman frontier policy and the (ethnic) recruitment of Germanic groups by the Roman military.Material Culture Studie

Comparative analysis between condom use clusters and risk behaviours among portuguese university students

The research on condom use has been focused on high-risk individuals, paying less attention to those who have moderate risk or safe sexual conducts. In order to design accurate interventions, potential differences among the condom use behavior groups must be considered. The goal was to assess possible differences in individuals presenting different types of risk behavior. 140 heterosexual university students answered a self-reported questionnaire about their sexual history, condom use habits, sexual self-esteem, sexual satisfaction, sexual control, attitudes towards condoms, self-efficacy to condom use, and emotions and feelings during sexual intercourse. A cluster analysis was conducted using the results about condom use and risk behaviors. Three groups with different risk levels emerged, presenting differences over sexual self-efficacy, attitudes towards condoms, socio-demographic variables, and sexual history. The results suggest the condom use inconsistency is highly associated with other risk behaviors but the contrary does not necessarily happens. Condom use consistent users also presented risk behaviors as smoking and drinking. The group differences suggest the risks were more affected by the combination of lack of skills with a negative attitude toward condoms than by contextual or personal variables. These differences sustain the need of an intervention adjusted to the individual's risk levels, since they differ on skills and beliefs that may hinder or promote the adoption of health behaviors.Foundation for Science and Technology/Fundacao para a Ciencia e Tecnologia (Portugal)info:eu-repo/semantics/publishedVersio

A Novel Function of Apolipoprotein E: Upregulation of ATP-Binding Cassette Transporter A1 Expression

Despite the well known importance of apolipoprotein (Apo) E in cholesterol efflux, the effect of ApoE on the expression of ATP-binding cassette transporter A1 (ABCA1) has never been investigated. The objective of this study was to determine the effect of ApoE on ApoB-carrying lipoprotein-induced expression of ABCA1, a protein that mediates cholesterol efflux. Our data demonstrate that ApoB-carrying lipoproteins obtained from both wild-type and ApoE knockout mice induced ApoAI-mediated cholesterol efflux in mouse macrophages, which was associated with an enhanced ABCA1 promoter activity, and an increased ABCA1 mRNA and protein expression. In addition, these lipoproteins increased the level of phosphorylated specificity protein 1 (Sp1) and the amount of Sp1 bound to the ABCA1 promoter. However, all these inductions were significantly diminished in cells treated with ApoE-free lipoproteins, when compared to those treated with wild-type lipoproteins. Enrichment with human ApoE3 reversed the reduced inducibility of ApoE-free lipoproteins. Moreover, we observed that inhibition of Sp1 DNA-binding by mithramycin A diminished ABCA1 expression and ApoAI-mediated cholesterol efflux induced by ApoB-carrying lipoproteins, and that mutation of the Sp1-binding motif in the ABCA1 promoter region diminished ApoB-carrying lipoprotein-induced ABCA1 promoter activity. Collectively, these data suggest that ApoE associated with ApoB-carrying lipoproteins has an upregulatory role on ABCA1 expression, and that induction of Sp1 phosphorylation is a mechanism by which ApoE upregulates ABCA1 expression

Protection of the Ovine Fetal Gut against Ureaplasma-Induced Chorioamnionitis: A Potential Role for Plant Sterols

Chorioamnionitis, clinically most frequently associated with Ureaplasma, is linked to intestinal inflammation and subsequent gut injury. No treatment is available to prevent chorioamnionitis-driven adverse intestinal outcomes. Evidence is increasing that plant sterols possess immune-modulatory properties. Therefore, we investigated the potential therapeutic effects of plant sterols in lambs intra-amniotically (IA) exposed to Ureaplasma. Fetal lambs were IA exposed to Ureaplasma parvum (U. parvum, UP) for six days from 127 d–133 d of gestational age (GA). The plant sterols β-sitosterol and campesterol, dissolved with β-cyclodextrin (carrier), were given IA every two days from 122 d–131 d GA. Fetal circulatory cytokine levels, gut inflammation, intestinal injury, enterocyte maturation, and mucosal phospholipid and bile acid profiles were measured at 133 d GA (term 150 d). IA plant sterol administration blocked a fetal inflammatory response syndrome. Plant sterols reduced intestinal accumulation of proinflammatory phospholipids and tended to prevent mucosal myeloperoxidase-positive (MPO) cell influx, indicating an inhibition of gut inflammation. IA administration of plant sterols and carrier diminished intestinal mucosal damage, stimulated maturation of the immature epithelium, and partially prevented U. parvum-driven reduction of mucosal bile acids. In conclusion, we show that β-sitosterol and campesterol administration protected the fetus against adverse gut outcomes following UP-driven chorioamnionitis by preventing intestinal and systemic inflammation

The distribution and degradation of radiolabeled superparamagnetic iron oxide nanoparticles and quantum dots in mice

No(51)Cr-labeled, superparamagnetic, iron oxide nanoparticles ((51)Cr-SPIOs) and (65)Zn-labeled CdSe/CdS/ZnS-quantum dots ((65)Zn-Qdots) were prepared using an easy, on demand, exchange-labeling technique and their particokinetic parameters were studied in mice after intravenous injection. The results indicate that the application of these heterologous isotopes can be used to successfully mark the nanoparticles during initial distribution and organ uptake, although the (65)Zn-label appeared not to be fully stable. As the degradation of the nanoparticles takes place, the individual transport mechanisms for the different isotopes must be carefully taken into account. Although this variation in transport paths can bring new insights with regard to the respective trace element homeostasis, it can also limit the relevance of such trace material-based approaches in nanobioscience. By monitoring (51)Cr-SPIOs after oral gavage, the gastrointestinal non-absorption of intact SPIOs in a hydrophilic or lipophilic surrounding was measured in mice with such high sensitivity for the first time. After intravenous injection, polymer-coated, (65)Zn-Qdots were mainly taken up by the liver and spleen, which was different from that of ionic (65)ZnCl2. Following the label for 4 weeks, an indication of substantial degradation of the nanoparticles and the release of the label into the Zn pool was observed. Confocal microscopy of rat liver cryosections (prepared 2 h after intravenous injection of polymer-coated Qdots) revealed a colocalization with markers for Kupffer cells and liver sinusoidal endothelial cells (LSEC), but not with hepatocytes. In J774 macrophages, fluorescent Qdots were found colocalized with lysosomal markers. After 24 h, no signs of degradation could be detected. However, after 12 weeks, no fluorescent nanoparticles could be detected in the liver cryosections, which would confirm our (65)Zn data showing a substantial degradation of the polymer-coated CdSe/CdS/ZnS-Qdots in the liver

INSPIRE: A European training network to foster research and training in cardiovascular safety pharmacology

Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate undesirable pharmacodynamic properties of a drug primarily prior to clinical trials. In particular, cardiovascular adverse drug reactions (ADR) have halted many drug development programs. Safety pharmacology has successfully implemented a screening strategy to detect cardiovascular liabilities, but there is room for further refinement. In this setting, we present the INSPIRE project, a European Training Network in safety pharmacology for Early Stage Researchers (ESRs), funded by the European Commission's H2020-MSCA-ITN programme. INSPIRE has recruited 15 ESR fellows that will conduct an individual PhD-research project for a period of 36 months. INSPIRE aims to be complementary to ongoing research initiatives. With this as a goal, an inventory of collaborative research initiatives in safety pharmacology was created and the ESR projects have been designed to be complementary to this roadmap. Overall, INSPIRE aims to improve cardiovascular safety evaluation, either by investigating technological innovations or by adding mechanistic insight in emerging safety concerns, as observed in the field of cardio-oncology. Finally, in addition to its hands-on research pillar, INSPIRE will organize a number of summer schools and workshops that will be open to the wider community as well. In summary, INSPIRE aims to foster both research and training in safety pharmacology and hopes to inspire the future generation of safety scientists