1,810 research outputs found

    Mouse vaccination with dendritic cells loaded with prion protein peptides overcomes tolerance and delays scrapie.

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    Prion diseases are presumed to be caused by the accumulation in the brain of a pathological protein called prion protein (PrP) scrapie which results from the transconformation of cellular PrP, a ubiquitous glycoprotein expressed in all mammals. Since all isoforms of PrP are perceived as self by the host immune system, a major problem in designing efficient immunoprophylaxis or immunotherapy is to overcome tolerance. The present study was aimed at investigating whether bone-marrow-derived dendritic cells (DCs) loaded with peptides previously shown to be immunogenic in PrP-deficient mice, can overcome tolerance in PrP-proficient wild-type mice and protect them against scrapie. Results show that, in such mice, peptide-loaded DCs elicit both lymphokine release by T cells and antibody secretion against native cellular PrP. Repeated recalls with peptide-loaded DCs reduces the attack rate of 139A scrapie inoculated intraperitoneally and retards disease duration by 40 days. Most interestingly, survival time in individual mice appears to be correlated with the level of circulating antibody against native cellular PrP

    Role of S/Se ratio in chemical bonding of As-S-Se glasses investigated by Raman, x-ray photoelectron, and extended x-ray absorption fine structure spectroscopies

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    Chalcogenide glasses have attracted considerable attention and found various applications due to their infrared transparency and other optical properties. The As-S-Se chalcogenide glass, with its large glass-formation domain and favorable nonlinear property, is a promising candidate system for tailoring important optical properties through modification of glass composition. In this context, a systematic study on ternary As-S-Se glass, chalcogen-rich versus well-studied stochiometric compositions, has been carried out using three different techniques: Raman spectroscopy, x-ray photoelectron spectroscopy, and extended x-ray absorption fine structure spectroscopy. These complementary techniques lead to a consistent understanding of the role of S/Se ratio in chalcogen-rich As-S-Se glasses, as compared to stochiometric composition, and to provide insight into the structural units (such as the mixed pyramidal units) and evidence for the existence of homopolar bonds (such as Se-Se, S-S, and Se-S), which are the possible structural origin of the high nonlinearity in these glasses

    A defective Krab-domain zinc-finger transcription factor contributes to altered myogenesis in myotonic dystrophy type 1

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    Myotonic dystrophy type 1 (DM1) is an RNA-mediated disorder caused by a non-coding CTG repeat expansion that, in particular, provokes functional alteration of CUG-binding proteins. As a consequence, several genes with misregulated alternative splicing have been linked to clinical symptoms. In our search for additional molecular mechanisms that would trigger functional defects in DM1, we took advantage of mutant gene-carrying human embryonic stem cell lines to identify differentially expressed genes. Among the different genes found to be misregulated by DM1 mutation, one strongly downregulated gene encodes a transcription factor, ZNF37A. In this paper, we show that this defect in expression, which derives from a loss of RNA stability, is controlled by the RNA-binding protein, CUGBP1, and is associated with impaired myogenesis—a functional defect reminiscent of that observed in DM1. Loss of the ZNF37A protein results in changes in the expression of the subunit α1 of the receptor for the interleukin 13. This suggests that the pathological molecular mechanisms linking ZNF37A and myogenesis may involve the signaling pathway that is known to promote myoblast recruitment during development and regeneratio

    The adrenal capsule is a signaling center controlling cell renewal and zonation through <i>Rspo3</i>

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    Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life

    Towards long-term social child-robot interaction: using multi-activity switching to engage young users

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    Social robots have the potential to provide support in a number of practical domains, such as learning and behaviour change. This potential is particularly relevant for children, who have proven receptive to interactions with social robots. To reach learning and therapeutic goals, a number of issues need to be investigated, notably the design of an effective child-robot interaction (cHRI) to ensure the child remains engaged in the relationship and that educational goals are met. Typically, current cHRI research experiments focus on a single type of interaction activity (e.g. a game). However, these can suffer from a lack of adaptation to the child, or from an increasingly repetitive nature of the activity and interaction. In this paper, we motivate and propose a practicable solution to this issue: an adaptive robot able to switch between multiple activities within single interactions. We describe a system that embodies this idea, and present a case study in which diabetic children collaboratively learn with the robot about various aspects of managing their condition. We demonstrate the ability of our system to induce a varied interaction and show the potential of this approach both as an educational tool and as a research method for long-term cHRI

    Liver Transudate, a Potential Alternative to Detect Anti-Hepatitis E Virus Antibodies in Pigs and Wild Boars (Sus scrofa)

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    In recent years, cases of hepatitis E virus (HEV) infection have increased in Europe in association with the consumption of contaminated food, mainly from pork products but also from wild boars. The animal’s serum is usually tested for the presence of anti-HEV antibodies and viral RNA but, in many cases such as during hunting, an adequate serum sample cannot be obtained. In the present study, liver transudate was evaluated as an alternative matrix to serum for HEV detection. A total of 125 sera and liver transudates were tested by enzyme-linked immunosorbent assay at different dilutions (1:2, 1:10, 1:20), while 58 samples of serum and liver transudate were checked for the presence of HEV RNA by RT-qPCR. Anti- HEV antibodies were detected by ELISA in 68.0% of the serum samples, and in 61.6% of the undiluted transudate, and in 70.4%, 56.8%, and 44.8% of 1:2, 1:10, or 1:20 diluted transudate, respectively. The best results were obtained for the liver transudate at 1:10 dilution, based on the Kappa statistic (0.630) and intraclass correlation coefficient (0.841). HEV RNA was detected by RT-qPCR in 22.4% of the serum samples and 6.9% of the transudate samples, all samples used for RT-qPCR were positive by ELISA. Our results indicate that liver transudate may be an alternative matrix to serum for the detection of anti-HEV antibodies
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