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

Thermal behavior of LV cables in presence of harmonic currents

International audienceThe proliferation of non-linear loads on public and industrial networks causes increases of harmonic current distortion. This paper deals with the thermal impact of harmonic distortion on LV cables, especially LV cables with neutral conductor. The thermal impact of harmonics is shown by measurements and FEM simulations on two different LV cable structures

Pembuatan Aplikasi Sistem Informasi Persebaran Toko Batik Di Kota Pekalongan Berbasis Android

Pekalongan is located in the lowlands along the north coast of Java Island, at a height of approximately one meter above sea level. The geographical position of Pekalongan is between 6° 50\u27 42" to 6° 55\u27 44\u27\u27 North Latitude and 109° 37\u27 55\u27\u27to 109° 42\u27 19\u27\u27 East Longitude.Pekalongan area of about 42.25 km2 or approximately 0.14% from the area of Central Java Province.Pekalongan is known by the nickname city of Batik, because batik Pekalongan has distinctive and varied livery. Therefore, Pekalongan is espected to provide a practical and informative information for tourists, so it can be an attraction and increase the number of tourists coming to Pekalongan. This research uses of spatial and non spasial data in the form of batik store name, the owner\u27s name, phone number, address, and products sold with using the popularity of android smartphone as a platform system information.This application was developed using an SDK Andoidframework, java and PHP programming languages, and MySQL as base data, and Google Maps. The final result of this research is the Android application of the distribution of batik store in Pekalongan is accompanied by information (as has been mentioned above) from each store for easier searching the location of the batik stores in Pekalonga

Vers une automatisation du contrôle visuel des produits

National audienc

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

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

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

Neurokinin-1 Receptor Signalling Impacts Bone Marrow Repopulation Efficiency

Tachykinins are a large group of neuropeptides with both central and peripheral activity. Despite the increasing number of studies reporting a growth supportive effect of tachykinin peptides in various in vitro stem cell systems, it remains unclear whether these findings are applicable in vivo. To determine how neurokinin-1 receptor (NK-1R) deficient hematopoietic stem cells would behave in a normal in vivo environment, we tested their reconstitution efficiency using competitive bone marrow repopulation assays. We show here that bone marrow taken from NK-1R deficient mice (Tacr1−/−) showed lineage specific B and T cell engraftment deficits compared to wild-type competitor bone marrow cells, providing evidence for an involvement of NK-1R signalling in adult hematopoiesis. Tachykinin knockout mice lacking the peptides SP and/or HK-1 (Tac1−/−, Tac4−/− and Tac1−/−/Tac4−/− mice) repopulated a lethally irradiated wild-type host with similar efficiency as competing wild-type bone marrow. The difference between peptide and receptor deficient mice indicates a paracrine and/or endocrine mechanism of action rather than autocrine signalling, as tachykinin peptides are supplied by the host environment