A small step closer to the Holy Grail of DNA vaccines: undisputed clinical benefit in humans

A report of the DNA Vaccines 2008 meeting, Las Vegas, Nevada, USA, 9-11 December 2008

Hypoxia modifies the feeding preferences of Drosophila. Consequences for diet dependent hypoxic survival

International audienceBACKGROUND: Recent attention has been given to the relationships between diet, longevity, aging and resistance to various forms of stress. Flies do not simply ingest calories. They sense different concentrations of carbohydrate and protein macronutrients and they modify their feeding behavior in response to changes in dietary conditions. Chronic hypoxia is a major consequence of cardiovascular diseases. Dietary proteins have recently been shown to decrease the survival of chronically hypoxic Drosophila. Whether flies modify their feeding behavior in response to hypoxia is not currently known. This study uses the recently developed capillary feeding assay to analyze the feeding behavior of normoxic and chronically hypoxic Drosophila melanogaster. RESULTS: The intakes rates of sucrose and yeast by normoxic or chronically hypoxic flies (5% O2) were analyzed under self selecting and "no choice" conditions. Chronically hypoxic flies fed on pure yeast diets or mixed diets under self selection conditions stopped feeding on yeast. Flies fed on mixed diets under "no choice" conditions reduced their food intakes. Hypoxia did not modify the adaptation of flies to diluted diets or to imbalanced diets. Mortality was assessed in parallel experiments. Dietary yeast had two distinct effects on hypoxic flies (i) a repellent action which eventually led to starvation and which was best observed in the absence of dietary sucrose and (ii) a toxic action which led to premature death. Finally we determined that hypoxic survivals were correlated to the intakes of sucrose, which suggested that dietary yeast killed flies by reducing their intake of sucrose. The feeding preferences of adult Drosophila were insensitive to NO scavengers, NO donor molecules and inhibitors of phosphodiesterases which are active on Drosophila larvae. CONCLUSION: Chronically hypoxic flies modify their feeding behavior. They avoid dietary yeast which appears to be toxic. Hypoxic survival is dependent on a source of exogenous sucrose. Ultimately, dietary yeast reduces hypoxic survival by reducing the intake of sucrose. The results highlight the importance of behavioral mechanisms in the responses of Drosophila to chronic hypoxic conditions

The role of polyamines in protein-dependent hypoxic tolerance of Drosophila

<p>Abstract</p> <p>Background</p> <p>Chronic hypoxia is a major component of ischemic diseases such as stroke or myocardial infarction. <it>Drosophila </it>is more tolerant to hypoxia than most mammalian species. It is considered as a useful model organism to identify new mechanisms of hypoxic tolerance. The hypoxic tolerance of flies has previously been reported to be enhanced by low protein diets. This study analyses the mechanisms involved.</p> <p>Results</p> <p>Feeding adult <it>Drosophila </it>on a yeast diet dramatically reduced their longevities under chronic hypoxic conditions (5% O₂). Mean and maximum longevities became close to the values observed for starving flies. The action of dietary yeast was mimicked by a whole casein hydrolysate and by anyone of the 20 natural amino acids that compose proteins. It was mimicked by amino acid intermediates of the urea cycle such as L-citrulline and L-ornithine, and by polyamines (putrescine, spermidine and spermine). α-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, partially protected hypoxic flies from amino acid toxicity but not from polyamine toxicity. N¹-guanyl-1,7 diaminoheptane, a specific inhibitor of eIF5A hypusination, partially relieved the toxicities of both amino acids and polyamines.</p> <p>Conclusion</p> <p>Dietary amino acids reduced the longevity of chronically hypoxic flies fed on a sucrose diet. Pharmacological evidence suggests that the synthesis of polyamines and the hypusination of eIF5A contributed to the life-shortening effect of dietary amino acids.</p

Strong Dietary Restrictions Protect Drosophila against Anoxia/Reoxygenation Injuries

Reoxygenation of ischemic tissues is a major factor that determines the severity of cardiovascular diseases. This paper describes the consequences of anoxia/reoxygenation (A/R) stresses on Drosophila, a useful, anoxia tolerant, model organism.Newly emerged adult male flies were exposed to anoxic conditions (<1% O2) for 1 to 6 hours, reoxygenated and their survival was monitored.A/R stresses induced a transient increase in mortality which peaked at the time of reoxygenation. Then flies recovered low mortality rates similar to those of control flies. A/R induced mortality was strongly dependent on dietary conditions during the 48 h that preceded anoxia. Well fed flies were anoxia sensitive. Strong dietary restrictions and starvation conditions protected flies against A/R injuries. The tolerance to anoxia was associated to large decreases in glycogen, protein, and ATP contents. During anoxia, anoxia tolerant flies produced more lactate, less phosphate and they maintained more stable ATP levels than anoxia sensitive flies. Moderate dietary restrictions, which increased the longevity of normoxic flies, did not promote resistance to A/R stresses. Diet dependent A/R injuries were still observed in sigma loss of function mutants and they were insensitive to dietary rapamycin or resveratrol. AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribose-furanoside), an activator AMP kinase decreased A/R injuries. Mutants in the insulin signalling pathway were more anoxia tolerant in a fed state.Long A/R stresses induce a transient increase in mortality in Drosophila. This mortality is highly dependent on dietary conditions prior to the stress. Strong dietary restrictions and starvation conditions protect flies against A/R injuries, probably by inducing a major remodelling of energy metabolism. The results also indicate that mechanistically different responses develop in response to dietary restrictions of different strengths. AMP kinase and the insulin signalling pathway are possible mediators of diet dependent anoxic tolerance in Drosophila

La relation fréquence-abondance. Aspects théoriques : application à un peuplement d'oiseaux

The frequency of a species (proportion of samples in which the species is recorded) is a non linear function of its abundance, which is modifieby the pattern of distribution of the individuals and by the surface of the area sampled. These parameters determine the probability of presence of a species. The probability of detection of an individual depends on species detectability and on the sampling duration. Several models are proposed to describe the influence of these parameters on the relationship between frequency and abundance, but it was not possible to deduce a general madel that includes all these parameters. Thus sampling conditions have to be carefully chosen in arder to control at least some of these parameters. The proposed models have been applied to a series of bird censuses performed by Blondel (Terre et Vie, 29 (1975) : 533-589) . Species frequencies were determined from 38 samplings and were transformed into species abundances using the models proposed in the first section of this paper. Species abundances derived from the frequencies agree fairly well with species abundances determined by direct sampling. The models proposed may have more general applications to samplings based on the presence or absence of a species

Peran Algemene Inlichtingen En Veiligheidsdients (AIVD) Dalam Pencegahan Islamic Radicalization Dan Homegrown Terrorism Di Belanda

Homegrown terrorism and islamic radicalisation is an action that distrub the national security. Therefore, the aim of this reserch is to understand the respon of the government and what kind of approach that they use to prevent those action. For this research qualitative is be use as the methodology and the type of research is descriptive research analysis and technique collecting data of the research is library research. Concept of this research is counterterrorisn, radicalisation and the theory is the four-wave that will be futher discuss about homegrown terrorism. Homegrown terrorism is being consider danger after the murder of Theo van Gogh in Amsterdam. The reason of the murdering is because one his attainments “the submmision”. Therefore, AIVD have role to prevent homegrown terrorism. Throug AIVD the analysis of the risk of teroris action can be able to detect before that could be seriously threat the national security

Blocking entry of hepatitis B and D viruses to hepatocytes as a novel immunotherapy for treating chronic infections

Background. Chronic hepatitis B and D virus (HBV/HDV) infections can cause cancer. Current HBV therapy using nucleoside analogues (NAs) is life-long and reduces but does not eliminate the risk of cancer. A hallmark of chronic hepatitis B is a dysfunctional HBV-specific T-cell response. We therefore designed an immunotherapy driven by naive healthy T cells specific for the HDV antigen (HDAg) to bypass the need for HBV-specific T cells in order to prime PreS1-specific T cells and PreS1 antibodies blocking HBV entry. Methods. Ten combinations of PreS1 and/or HDAg sequences were evaluated for induction of PreS1 antibodies and HBV- and HDV-specific T cells in vitro and in vivo. Neutralization of HBV by PreS1-specific murine and rabbit antibodies was evaluated in cell culture, and rabbit anti-PreS1 were tested for neutralization of HBV in mice repopulated with human hepatocytes. Results. The best vaccine candidate induced T cells to PreS1 and HDAg, and PreS1 antibodies blocking HBV entry in vitro. Importantly, adoptive transfer of PreS1 antibodies prevented, or modulated, HBV infection after a subsequent challenge in humanized mice. Conclusions. We here describe a novel immunotherapy for chronic HBV/HDV that targets viral entry to complement NAs and coming therapies inhibiting viral maturation

A site-plan-proposal for the Geosite Osmundsberg

Mot bakgrund av den ökade geologiska turismen världen över, väcktes för flera år sedan idén att skapa Sveriges första internationella geopark, ett område i landskapet med utmarkerade geovetenskapliga besöksmål. Projekt Meteorum arbetar idag för att förverkliga denna idé i Siljansbygden, Dalarna. Denna geopark har sin utgångspunkt i ett av de största meteoritnedslagen i jordens historia, och ämnar visa upp dess geologiska efterverkningar. Geoparken skall också visa hur denna kosmiska händelse har påverkat människors liv i Siljansbygden fram till våra dagar. Projekt Meteorum har i dagsläget cirka 25 utmarkerade geologiskt intressanta platser som initialt skall ingå i denna geopark. Syftet med denna uppsats är att genom ett gestaltningsförslag visa hur en geologisk besöksupplevelse kan se ut vid Osmundsberg, en av projekt Meteorums utvalda platser. Uppsatsen skall inom ramen för en geopark visa hur en gestaltning kan förstärka platsen och dess historia. I gestaltningen har vi använt oss av en förebild; Sohlbergsplassen, en anläggning i projektet Norsk Turistveg. Detta gav oss ett förhållningssätt som vi sedan applicerade på vårt eget gestaltningsförslag. Uppsatsen diskuterar även hur man kan levandegöra geologi, och hur ett arkitektoniskt tillägg, tillsammans med den befintliga platsen, kan skapa mervärden. Detta kandidatarbete ger först en närmare introduktion i geoturism, geoparker och projekt Meteorum. Förstudie och platsbesök mynnade sedan ut i ett gestaltningsförslag för Osmundsbergs kalkbrott. Förslaget innefattar en besöksanläggning med besökscenter och utsiktsbalkong. Fokus ligger på hur den geologiska historien kan berättas med hjälp av arkitektur. Vår förhoppning är att vår analys och vårt förslag kan hjälpa och inspirera vid en eventuell framtida anläggning av en geosite vid Osmundsbergs kalkbrott. Syftet är även att undersöka vad vår gestaltning kan ge till konceptet geopark och hur konceptet kan utvecklas av landskapsarkitekter. Slutligen diskuteras vårt eget resultat, vi återkopplar till syftet och diskuterar utveckling av geoparker ur ett landskapsarkitektoniskt perspektiv.In the light of recent years increased interest in geological tourism around the world, the project group Meteorum started its work towards creating Sweden’s first international geopark; an area in the landscape with geologically interesting sites. This geopark in the Siljan district, Dalarna, aims to display one of the worlds heaviest meteorite-impacts and its geological after-effects. The geopark also aims to demonstrate how this cosmic event has had an effect on every-day life in the Siljan district over the centuries. Project Meteorum currently has 25 geosites, sites with geological points of interest, connected to the prospected geopark. The purpose of this is essay is to show, through a site-design proposal, how the experience of a visit to the geosite Osmundsberg might look like. The proposal also aims to show how a design can enhance the site and its history in the context of a geopark. We have used an architectural role model; Sohlbergsplassen, a part of the project Norsk Turistveg, and applied its guidelines to our own design. The essay also discusses how to bring geology to life, and how an architectural installation, together with the existing values, can create added value to the place. This essay will first give a introduction to geoturism, geoparks and the Meteorum projekt. A historic pre-study of Osmundsberg and a site visit then resulted in a site-design proposal.The aim is also to investigate how an architectural installation can profit to the geopark concept, and how this can get developed by landscape architects. Finally we discuss our result and how it answers to the main purpose of this essay. Furthermore we discuss the development of the geopark concept from a landscape-architectural perspective