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Arboviral diseases are a growing global health concern. Pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) can underlie encephalitis due to West Nile virus (WNV) (∼40% of patients) and tick-borne encephalitis (TBE, due to TBE virus [TBEV]) (∼10%). We report here that these auto-Abs can also underlie severe forms of rarer arboviral infections. Auto-Abs neutralizing high concentrations of IFN-α2, IFN-β, and/or IFN-ω are present in the single case of severe Powassan virus (POWV) encephalitis studied, two of three cases of severe Usutu virus (USUV) infection studied, and the most severe of 24 cases of Ross River virus (RRV) disease studied. These auto-Abs are not found in any of the 137 individuals with silent or mild infections with these three viruses. Thus, auto-Abs neutralizing type I IFNs underlie an increasing list of severe arboviral diseases due to Flaviviridae (WNV, TBEV, POWV, USUV) or Togaviridae (RRV) viruses transmitted to humans by mosquitos (WNV, USUV, RRV) or ticks (TBEV, POWV).

L’autonomie du patient est au cœur de la prise en charge en douleur chronique, à la fois comme principe éthique à respecter et comme objectif thérapeutique à atteindre pour améliorer la qualité de vie du sujet. La décision médicale partagée est un des moyens reconnus pour respecter, voire renforcer cette autonomie via un processus de délibération qui aide les patients à mettre les informations en perspective et qui respecte ce qu’ils jugent important. Nous décrirons dans cet article les spécificités de ce modèle appliqué à la douleur chronique.

Many physiological functions are regulated by free fatty acids (FFA). Recently, the discovery of FFA-specific G protein-coupled receptors (FFARs) has added to the complexity of their actions at the cellular level. The study of FFAR in cattle is still in its earliest stages focusing mainly on dairy cows. In this study, we set out to map the expression of genes encoding FFARs in 6 tissues of beef cattle. We also investigated the potential effect of dietary forage nature on FFAR gene expression. To this end, 16 purebred Charolais bulls were fed a grass silage ration or a maize silage ration (n= 8/group) with a forage/concentrate ratio close to 60:40 for 196 d. The animals were then slaughtered at 485 ± 42 d and liver, spleen, ileum, rectum, perirenal adipose tissue (PRAT), and Longissimus Thoracis muscle were collected. FFAR gene expression was determined by real-time quantitative PCR. Our results showed that of the five FFARs investigated, FFAR1, FFAR2, FFAR3, and GPR84 are expressed (Ct < 30) in all six tissues, whereas FFAR4 was only expressed (Ct < 30) in PRAT, ileum, and rectum. In addition, our results showed that the nature of the forage, i.e., grass silage or maize silage, had no effect on the relative abundance of FFAR in any of the tissues studied (Pvalue > 0.05). Taken together, these results open new perspectives for studying the physiological role of these receptors in beef cattle, particularly in nutrient partitioning during growth.Our study shows that free fatty acid receptors are expressed in a wide range of beef cattle tissues. It opens new perspectives to better understand the mode of action of free fatty acids at tissue level in cattle.Free fatty acids (FFA) are key modulators of bovine physiology. Recently, it has been discovered that some G protein-coupled receptors, termed free fatty acid receptors (FFARs), may help mediate the action of FFA at the cellular level. In humans and rodents, a growing body of evidence has shown that i) FFARs are expressed in a wide range of tissues and ii) FFARs are involved in the regulation of major FFA-dependent physiological processes (inflammation, feed intake, insulin release, etc.). In cattle, information on FFAR expression and function in tissues are scarce and mainly concern dairy cows. In this study, we showed that FFARs are expressed in 6 different tissues of beef cattle: adipose tissue, muscle tissue, ileum, rectum, liver, and spleen. We also showed that the nature of forage fed to the animals (i.e., grass silage vs. maize silage) has no effect on FFARs gene expression.

ABSTRACTKingella kingaeis an important invasive pathogen in early childhood. The organism elaborates an RTX toxin presumably restricted to this species. Consequently, real-time quantitative PCR (qPCR) assays targeting the RTX locus have been developed in recent years and are gaining increasing use for the molecular diagnosis of K. kingaeinfections. However, the present study shows that Kingella negevensis, a Kingellaspecies newly identified in young children, harbors an identical KingellaRTX locus, raising the question of whether K. negevensiscan be misidentified as K. kingaeby clinical microbiology laboratories. In silicocomparison of Kingellasp. RTX and groELgenes and in vitrostudies provided evidence that targeting the rtxAand rtxBgenes could not differentiate between strains of K. kingaeand K. negevensis, whereas targeting the groELgene could. This prompted the design of a highly specific and sensitive qPCR assay targeting K. negevensis groEL(kngroEL). Ninety-nine culture-negative osteoarticular specimens from 99 children younger than 4 years of age were tested with a conventional 16S rRNA gene-based broad-range PCR assay and Kingella-specific rtxB, K. kingae-specific groEL(kkgroEL), and kngroELqPCR assays. Forty-two specimens were rtxBpositive, including 41 that were also kkgroELpositive and 1 (the remaining one) that was kngroELpositive. Thus, this study discloses an invasive infection caused by K. negevensisin humans and demonstrates that targeting the RTX locus cannot be used for the formal diagnosis of K. kingaeinfections. These findings stress the need for further studies on the epidemiology of asymptomatic carriage and invasive infections caused by K. negevensisin humans.

RNA molecules uniquely form a complex through specific hairpin loops, called a kissing complex. The kissing complex is widely investigated and used for the construction of RNA nanostructures. Molecular switches have also been created by combining a kissing loop and a ligand-binding aptamer to control the interactions of RNA molecules. In this study, we incorporated two kinds of RNA molecules into a DNA origami structure and used atomic force microscopy to observe their ligand-responsive interactions at the single-molecule level. We used a designed RNA aptamer called GTPswitch, which has a guanosine triphosphate (GTP) responsive domain and can bind to the target RNA hairpin named Aptakiss in the presence of GTP. We observed shape changes of the DNA/RNA strands in the DNA origami, which are induced by the GTPswitch, into two different shapes in the absence and presence of GTP, respectively. We also found that the switching function in the nanospace could be improved by using a cover strand over the kissing loop of the GTPswitch or by deleting one base from this kissing loop. These newly designed ligand-responsive aptamers can be used for the controlled assembly of the various DNA and RNA nanostructures.

Over the past decade, the development of web-based Geographic Information Systems (GIS) for health has grown quite rapidly due to an increased need of data integration and spatial visualization. One GIS growth area in health is the construction of map-based applications that provide information on health care resources. Such applications are typically used as standard tools by public health departments, public health policy and research organizations, hospitals and health insurance organizations to provide public access to health care resources. This paper presents the design and development process of Clinic Finder (CliFin) - an open-access web-based GIS application relying on the Google Maps technology and providing access to a database with point of care facilities across the Province of New Brunswick, Canada. The uniqueness of CliFin consists in the implementation of a time-frame dependent search and results trimming approach, which allows users to identify clinics and hospitals open at any given time. The users are also encouraged to contribute with schedule updates and new point of care information to further develop CliFin’s database and its accuracy. The combination of GIS visualization capabilities, database management, user involvement in database update and the time-frame dependence of search results, confers CliFin increased practicality, especially in situations of crisis such as natural disasters.

ABSTRACTYersinia pestisis the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestisis a protective antigen under development as a recombinant vaccine. However, little is known about the specificity of human T-cell responses for Caf1. We characterized CD4 T-cell epitopes of Caf1 in “humanized” HLA-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules. Mice were immunized with Caf1 or each of a complete set of overlapping synthetic peptides, and CD4 T-cell immunity was measured with respect to proliferative and gamma interferon T-cell responses and recognition by a panel of T-cell hybridomas, as well as direct determination of binding affinities of Caf1 peptides to purified HLA-DR molecules. Although a number of DR1-restricted epitopes were identified following Caf1 immunization, the response was biased toward a single immunodominant epitope near the C terminus of Caf1. In addition, potential promiscuous epitopes, including the immunodominant epitope, were identified by their ability to bind multiple common HLA alleles, with implications for the generation of multivalent vaccines against plague for use in humans.

Yersinia pestis is the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestis is a protective antigen under development as a recombinant vaccine. However, little is known about the specificity of human T-cell responses for Caf1. We characterized CD4 T-cell epitopes of Caf1 in "humanized" HLA-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules. Mice were immunized with Caf1 or each of a complete set of overlapping synthetic peptides, and CD4 T-cell immunity was measured with respect to proliferative and gamma interferon T-cell responses and recognition by a panel of T-cell hybridomas, as well as direct determination of binding affinities of Caf1 peptides to purified HLA-DR molecules. Although a number of DR1-restricted epitopes were identified following Caf1 immunization, the response was biased toward a single immunodominant epitope near the C terminus of Caf1. In addition, potential promiscuous epitopes, including the immunodominant epitope, were identified by their ability to bind multiple common HLA alleles, with implications for the generation of multivalent vaccines against plague for use in humans.

Kingella kingaeis a significant pediatric pathogen responsible for bone and joint infections, occult bacteremia, and endocarditis in early childhood. Past efforts to detect this bacterium using culture and broad-range 16S rRNA gene PCR assays from clinical specimens have proven unsatisfactory; therefore, by the late 2000s, these were gradually phased out to explore the benefits of specific real-time PCR tests targeting the groELgene and the RTX locus of K. kingae.