Localization of the N-terminal domain of cauliflower mosaic virus coat protein precursor

AbstractCauliflower mosaic virus (CaMV) open reading frame (ORF) IV encodes a coat protein precursor (pre-CP) harboring an N-terminal extension that is cleaved off by the CaMV-encoded protease. In transfected cells, pre-CP is present in the cytoplasm, while the processed form (p44) of CP is targeted to the nucleus, suggesting that the N-terminal extension might be involved in keeping the pre-CP in the cytoplasm for viral assembly. This study reports for the first time the intracellular localization of the N-terminal extension during CaMV infection in Brassica rapa. Immunogold-labeling electron microscopy using polyclonal antibodies directed to the N-terminal extension of the pre-CP revealed that this region is closely associated with viral particles present in small aggregates, which we called small bodies, adjacent to the main inclusion bodies typical of CaMV infection. Based on these results, we propose a model for viral assembly of CaMV

Development of a versatile vaccination platform based on papaya mosaic virus (PapMV) nanoparticles

Over the past years, virus-like particles (VLPs) have shown great potential as highly immunogenic subunit vaccines. These non-infectious viral structures mimic the native pathogen’s organisation and conformation. VLPs contain highly repetitive and ordered viral epitopes leading to B cell activation through receptor cross-linking. By displaying heterologous epitopes on VLPs, one can mount an immune response against a different pathogen. These chimeric VLPs serve as presentation scaffold and can sometimes act as adjuvant to boost the immune response. However, VLP assembly can be affected by large epitope insertions altering intra or extra protein interactions impacting its conformation. Even if the insertion is successful, the epitopes have to be exposed at the particle surface to induce an immune response. To circumvent this problem, we have developed a new vaccine platform based on PapMV nanoparticules and sortase A (SrtA) transpeptidase. SrtA catalyzes the covalent conjugation of target antigenic epitopes to already assembled PapMV VLPs harbouring the SrtA recognition motif LPETG. Successful SrtA conjugations were achieved with peptides derived from Influenza (M2e) and HIV (T20). SrtA conjugated PapMV nanoparticles induce strong humoral responses in mice against both M2e and T20 peptides. PapMV-M2e vaccinated mice were protected against a lethal dose of Influenza H1N1 (A/WSN/33). Sera from PapMV-T20 vaccinated mice did not reduce in vitro HIV infection even with the high presence of specific antibodies. This new PapMV-SrtA platform eliminates the need for genetic fusion of the coat protein that can be difficult, time consuming and, sometime, unrealizable. The modification of PapMV VLP post-assembly facilitates its use in the rapid development of new vaccines by changing the nature of the target epitopes conjugated. This could be particularly useful when developing a pandemic vaccine or personalised vaccine for cancer therapy

Engineering of Papaya Mosaic Virus (PapMV) Nanoparticles through Fusion of the HA11 Peptide to Several Putative Surface-Exposed Sites

Papaya mosaic virus has been shown to be an efficient adjuvant and vaccine platform in the design and improvement of innovative flu vaccines. So far, all fusions based on the PapMV platform have been located at the C-terminus of the PapMV coat protein. Considering that some epitopes might interfere with the self-assembly of PapMV CP when fused at the C-terminus, we evaluated other possible sites of fusion using the influenza HA11 peptide antigen. Two out of the six new fusion sites tested led to the production of recombinant proteins capable of self assembly into PapMV nanoparticles; the two functional sites are located after amino acids 12 and 187. Immunoprecipitation of each of the successful fusions demonstrated that the HA11 epitope was located at the surface of the nanoparticles. The stability and immunogenicity of the PapMV-HA11 nanoparticles were evaluated, and we could show that there is a direct correlation between the stability of the nanoparticles at 37°C (mammalian body temperature) and the ability of the nanoparticles to trigger an efficient immune response directed towards the HA11 epitope. This strong correlation between nanoparticle stability and immunogenicity in animals suggests that the stability of any nanoparticle harbouring the fusion of a new peptide should be an important criterion in the design of a new vaccine

L’influence des relations familiales et sociales sur la consommation de médicaments psychotropes chez les personnes âgées

Les psychotropes occupent le deuxième rang dans la consommation de médicaments chez les personnes âgées. L'objectif de cette étude est de vérifier un modèle explicatif de la consommation de psychotropes dans cette population. Notre principale hypothèse est que la qualité des relations qu'entretient une personne âgée avec autrui, et particulièrement avec ses enfants, a une influence directe sur son bien-être psychologique, lequel a une influence directe sur la non-consommation de psychotropes. Une enquête a été réalisée auprès d'un échantillon de 500 personnes âgées de 65 à 84 ans, vivant à domicile. Au cours des trois mois précédant l'entrevue, 31,8 % des répondants ont consommé des psychotropes. Les données empiriques n'ayant pas permis de vérifier le modèle théorique retenu, des analyses multivariées ont conduit à l'élaboration d'un modèle explicatif de la consommation qui met en évidence que le bien-être psychologique et la santé sont les meilleurs prédicteurs de cette consommation. Un bien-être psychologique élevé diminue la consommation alors qu'un mauvais état de santé l'augmente. Les relations sociales influencent directement le bien-être psychologique alors que les relations familiales ont un effet de moindre importance. Le modèle explicatif proposé explique 13 % du phénomène de la consommation de psychotropes chez les personnes âgées.Psychotropic drugs are the second most commonly used medication by Quebec's elderly. The objective of this study is to test a theoretical model of psychotropic drug use in the elderly. The principal hypothesis is that the quality of relationships the elderly person has with others, particularly with his or her children, has a direct influence on his or her psychological well-being, which, in turn, directly affects the consumption of psychotropic agents. A survey was conducted on a sample of 500 elderly people, aged 65-84 years, living at home. 31.8% of the respondents used psychotropic drugs during the three-month period preceding the interview. Path analysis led to the elaboration of a modified model for the consumption of psychotropic drugs by the elderly which indicates that the best predictors of consumption are both the psychological well-being and the state of health of the individual. More elevated is the psychological well-being, less is the consumption of psychotropic drugs, whereas poor health condition increases it. The quality of an individual's social relationships has a direct influence on his or her psychological well-being, whereas family relationships are of lesser importance. Our model accounts for 13% of the predictors of psychotropic consumption by the elderly

Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants.

International audienceVaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease

The papaya mosaic virus (PapMV) nanoparticles; a promising tool in vaccine development.

There is a major need for the development of new technologies that will facilitate the speed of development of vaccine and show a very high safety profile. In the last 10 years, we have developed a new toll like receptor agonist (TLR) that can trigger innate immunity follow by a strong adaptive immune response. This new agonist targets specifically the TLR7/8 in the endosome of the immune cells. It is made of the coat protein (CP) of a plant virus self-assembled around an RNA that forms flexuous rod-shape nanoparticles of 15x100nm. The highly repetitive and crystalline nature of the nanoparticles are attractive to immune cells leading to its internalization into the endosome where the nanoparticles is broken down by the harsh conditions of this compartment which liberate the RNA that trigger TLR7/8 to induce innate immunity. Therefore, we can use those nanoparticles as an adjuvant and improve the immune response to an antigen or as an immune modulator through the trigger of innate immunity that can induce protection to viral infection or improve the immune response to tumour. Finally, we have showed that we can engineered the nanoparticles into a vaccine platform through fusion of B or T cell epitope at its surface and elicits an efficient and protective immune response to the fused epitope. We will discuss the advantage of using this platform in vaccine development or cancer immunotherapy and show several examples where it has been shoed to be efficient and promising

A Type System for Privacy Properties (Technical Report)

Mature push button tools have emerged for checking trace properties (e.g. secrecy or authentication) of security protocols. The case of indistinguishability-based privacy properties (e.g. ballot privacy or anonymity) is more complex and constitutes an active research topic with several recent propositions of techniques and tools. We explore a novel approach based on type systems and provide a (sound) type system for proving equivalence of protocols, for a bounded or an unbounded number of sessions. The resulting prototype implementation has been tested on various protocols of the literature. It provides a significant speed-up (by orders of magnitude) compared to tools for a bounded number of sessions and complements in terms of expressiveness other state-of-the-art tools, such as ProVerif and Tamarin: e.g., we show that our analysis technique is the first one to handle a faithful encoding of the Helios e-voting protocol in the context of an untrusted ballot box

Préjugé dans la détermination des peines accordées aux jeunes doublement insérés dans le système public de protection et de justice

Les jeunes à double statut ou sous double autorité (crossover youth) sont des adolescents ayant été victimes de maltraitance et qui sont aussi auteurs d’une infraction criminelle. Une étude a montré que ces jeunes reçoivent généralement des peines plus sévères que les contrevenants n’ayant jamais été en contact avec le système de protection de la jeunesse, ce qui indiquerait la présence d’un préjugé dans la détermination des peines à leur égard. L’objectif de la présente étude est de contribuer à cette seule analyse réalisée sur le sujet en abordant la question de l’effet du double statut du jeune dans la détermination de sa peine, après le contrôle des principales covariables et l’analyse des différences de genre. À l’aide des dossiers officiels d’adolescents québécois ayant plaidé coupables ou ayant été condamnés pour un délit, de 2005 à 2010, un modèle de régression logistique prédisant les peines d’emprisonnement a été établi. Il semblerait que les incidents passés de maltraitance d’un jeune prédiraient l’infliction d’une peine d’emprisonnement dans le cas des jeunes à double statut de sexe masculin, et ce, même en tenant compte de l’âge, de l’origine ethnique, du type et de la gravité de l’infraction. En s’appuyant sur les résultats de cette analyse, des études plus approfondies devraient se pencher sur l’efficacité de ces peines dans la modification du comportement des contrevenants et la sécurité au sein de la famille

One-Year Safety Analysis of the COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133+ Bone Marrow Stem Cells to Placebo in Patients after Acute Myocardial Infarction and Left Ventricular Dysfunction

Bone marrow stem cell therapy has emerged as a promising approach to improve healing of the infarcted myocardium. Despite initial excitement, recent clinical trials using non-homogenous stem cells preparations showed variable and mixed results. Selected CD133+ hematopoietic stem cells are candidate cells with high potential. Herein, we report the one-year safety analysis on the initial 20 patients enrolled in the COMPARE-AMI trial, the first double-blind randomized controlled trial comparing the safety, efficacy, and functional effect of intracoronary injection of selected CD133+ cells to placebo following acute myocardial infarction with persistent left ventricular dysfunction. At one year, there is no protocol-related complication to report such as death, myocardial infarction, stroke, or sustained ventricular arrhythmia. In addition, the left ventricular ejection fraction significantly improved at four months as compared to baseline and remained significantly higher at one year. These data indicate that in the setting of the COMPARE-AMI trial, the intracoronary injection of selected CD133+ stem cells is secure and feasible in patients with left ventricle dysfunction following acute myocardial infarction

Good News — Bad News: Combined Ocean Change Drivers Decrease Survival but Have No Negative Impact on Nutritional Value and Organoleptic Quality of the Northern Shrimp

Nutritional and organoleptic qualities (taste, smell, texture, appearance) are key characteristics of seafood when it comes to defining consumer choices. These qualities, which are determined by the biochemical properties of the seafood, can be altered by environmental conditions, such as those imposed by ongoing global ocean change. However, these effects have rarely been studied despite their potential important economic and dietary implications: many human communities depend upon seafood as a primary source of nutrition and/or income from the associated seafood industry. The Northern shrimp, Pandalus borealis, makes the 3rd most valuable fishery in Eastern Canada, and figures among the most important fisheries in the North-Eastern Atlantic. This study aimed to determine the impact of combined ocean warming, acidification and hypoxia on (a) muscle mineral content as proxy for nutritional quality, and (b) the taste, smell, texture, and appearance as proxies for organoleptic quality of this commercially important species. These proxies were determined after an exposure of 30 days under laboratory conditions to different ocean global change scenarios of temperature (2, 6, and 10°C), pH (7.75 and 7.4) and oxygen (100 and 35% relative to air saturation), in isolation and in combination. Shrimp survival was significantly lower (68%) for shrimp exposed to warming and low pH, and even lower (37%) when hypoxia was superimposed, compared to an average survival of 88% for all other treatments. Mineral contents were globally higher in shrimp exposed to the highest temperature, while organoleptic attributes were comparable across all scenarios tested. Thus, while we do not expect nutritional value and organoleptic quality of shrimp, broadly speaking, to be altered by global changes even in areas where conditions will correspond to our warmest (10°C) and lowest pH (7.4) scenarios, the lower survival rate we report could negatively impact the viability of shrimp populations and consequently the shrimp industry. This may be particularly true for areas that are currently becoming or are expected to become hypoxic. -- Keywords : Ocean warming ; Ocean acidification ; Hypoxia ; Sensory quality ; Mortality ; Seafood