Pathogenic prions deviate PrP(C) signaling in neuronal cells and impair A-beta clearance.

The subversion of the normal function exerted by the cellular prion protein (PrP(C)) in neurons by pathogenic prions is assumed to have a central role in the pathogenesis of transmissible spongiform encephalopathies. Using two murine models of prion infection, the 1C11 neuronal cell line and neurospheres, we document that prion infection is associated with the constitutive activation of signaling targets normally coupled with PrP(C), including the Fyn kinase, the mitogen-associated protein kinases ERK1/2 and the CREB transcription factor. PrP(C)-dependent signaling overactivation in infected cells is associated with the recruitment of p38 and JNK stress-associated kinases. Downstream from CREB, prion-infected cells exhibit reduced activity of the matrix metalloprotease (MMP)-9. As MMP-9 catalyzes the degradation of the amyloid A-beta peptide, the decrease in MMP-9 activity in prion-infected cells causes a significant impairment of the clearance of A-beta, leading to its accumulation. By exploiting two 1C11-infected clones accumulating high or moderate levels of prions, we show that the prion-induced changes are correlated with the level of infectivity. Of note, a dose-dependent increase in A-beta levels was also found in the cerebrospinal fluid of mice inoculated with these infected clones. By demonstrating that pathogenic prions trigger increases in A-beta levels through the deviation of PrP(C) signaling, our data argue that A-beta may exacerbate prion-induced toxicity.

The past and present threat of vector-borne diseases in deployed troops.

From time immemorial, vector-borne diseases have severely reduced the fighting capacity of armies and caused suspension or cancellation of military operations. Since World War I, infectious diseases have no longer been the main causes of morbidity and mortality among soldiers. However, most recent conflicts involving Western armies have occurred overseas, increasing the risk of vector-borne disease for the soldiers and for the displaced populations. The threat of vector-borne disease has changed with the progress in hygiene and disease control within the military: some diseases have lost their military significance (e.g. plague, yellow fever, and epidemic typhus); others remain of concern (e.g. malaria and dengue fever); and new potential threats have appeared (e.g. West Nile encephalitis and chikungunya fever). For this reason, vector control and personal protection strategies are always major requirements in ensuring the operational readiness of armed forces. Scientific progress has allowed a reduction in the impact of arthropod-borne diseases on military forces, but the threat is always present, and a failure in the context of vector control or in the application of personal protection measures could allow these diseases to have the same devastating impact on human health and military readiness as they did in the past.

Sialome individuality between Aedes aegypti colonies.

Aedes aegypti is responsible for the transmission of arboviruses. The Yellow Fever, Dengue and Chikungunya viruses are transmitted to the vertebrate host by injection of infected saliva during the blood meal of its vectors. Saliva contains different components with various biochemical activities; anti-hemostatic, angiogenic, inflammatory, and immunomodulatory. This work compares the sialomes of three Ae. aegypti colonies (Rockefeller, PAEA, and Formosus), where the repertoire of salivary proteins from these colonies was analyzed by a proteomic approach. This study indicated that major proteins were detectable in the three colonies. However, differences in the abundance of some saliva proteins have been observed between the three Ae. aegypti colonies.

[Proteomic analysis and parasitosis: principles and applications]. / Analyses protéomiques et parasitoses: principes et applications.

O'Farrel described a method allowing two-dimensional (2D) protein separation more than 30 years ago. Since then the original technique has made enormous progress. This progress has been accompanied by advances in mass spectrometry technology as well as various genome-sequencing programs. Today 2D electrophoresis has become the workhorse of proteomics, allowing resolution of complex structures containing thousands of proteins and providing a global view of the state of a proteome. This article presents the different steps and limitations of proteomic analysis: preparation of biological material, 2D electrophoresis, protein detection systems, and available tools for protein identification. Alternative proteomic approaches to 2D electrophoresis are also presented. A few applications are described as examples to illustrate the utility of proteomic analysis for studying the mechanisms underlying virulence, resistance to antimalarial therapies and immune response against pathologic agents.

[Vectors of malaria: biology, diversity, prevention, and individual protection]. / Vecteurs du paludisme: biologie, diversité, contrôle et protection individuelle.

Only the Anopheles mosquitoes are implicated in the transmission of malaria. Among the numerous species of anopheles, around fifty are currently involved in the transmission. 20 are responsible for most of the transmission in the world. The diversity of behavior between species and in a single species of anopheles as well as climatic and geographical conditions along with the action of man on the environment condition the man vector contact level and the various epidemiological aspects of malaria. The anopheles are primarily rural mosquitoes and are less likely to be found in city surroundings in theory. But actually, the adaptation of some species to urban surroundings and the common habit of market gardening in big cities or in the suburbs is responsible for the de persistence of Anopheles populations in town. Except for South-East Asia, urban malaria has become a reality. The transmission risk of malaria is heterogeneous and varies with time. There is a great variation of risk within a same country, a same zone, and even within a few kilometers. The transmission varies in time according to seasons but also according to years and to the level of climatic events. For the traveler, prevention at any time relies on the strict application of individual protection, as well in rural than in urban surroundings.

[Malaria vaccines: prospects and reality]. / Vaccins contre le paludisme: perspectives et réalité

The development of a malaria vaccine has been accelerating in the last ten years. The number of clinical trials has increased and some malaria antigens have been tested in endemic areas. No potential vaccine has yet shown sufficient and lasting efficacy to justify its inclusion in a public health program. However, trials have unambiguously shown that some level of anti-malaria clinical immunity can be achieved by vaccination, both in experimental and in field conditions. Advances in malaria vaccine development are presented.

Optical imaging of luminescence for in vivo quantification of gene electrotransfer in mouse muscle and knee.

BACKGROUND: Optical imaging is an attractive non-invasive way to evaluate the expression of a transferred DNA, mainly thanks to its lower cost and ease of realization. In this study optical imaging was evaluated for monitoring and quantification of the mouse knee joint and tibial cranial muscle electrotransfer of a luciferase encoding plasmid. Optical imaging was applied to study the kinetics of luciferase expression in both tissues. RESULTS: The substrate of luciferase (luciferin) was injected either intraperitonealy (i.p.) or in situ into the muscle or the knee joint. Luminescence resulting from the luciferase-luciferin reaction was measured in vivo with a cooled CCD camera and/or in vitro on tissue lysate. Maximal luminescence of the knee joint and muscle after i.p. (2.5 mg) or local injection of luciferin (50 microg in the knee joint, 100 microg in the muscle) were highly correlated. With the local injection procedure adopted, in vivo and in vitro luminescences measured on the same muscles significantly correlated. Luminescence measurements were reproducible and the signal level was proportional to the amount of plasmid injected. In vivo luciferase activity in the electrotransfered knee joint was detected for two weeks. Intramuscular electrotransfer of 0.3 or 3 microg of plasmid led to stable luciferase expression for 62 days, whereas injecting 30 microg of plasmid resulted in a drop of luminescence three weeks after electrotransfer. These decreases were partially associated with the development of an immune response. CONCLUSION: A particular advantage of the i.p. injection of substrate is a widespread distribution at luciferase production sites. We have also highlighted advantages of local injection as a more sensitive detection method with reduced substrate consumption. Besides, this route of injection is relatively free of uncontrolled parameters, such as diffusion to the target organ, crossing of biological barriers and evidencing variations in local enzymatic kinetics, probably related to the reaction medium in the targeted organ. Optical imaging was shown to be a sensitive and relevant technique to quantify variations of luciferase activity in vivo. Further evaluation of the effective amount of luciferase in a given tissue by in vivo optical imaging relies on conditions of the enzymatic reaction and light absorption and presently requires in vitro calibration for each targeted organ.

[Metallocenes and malaria: a new therapeutic approach]. / Métallocènes et paludisme: une nouvelle approche thérapeutique.

Rapid development of significant resistance to antimalarial drugs has been a major force driving research to identify and develop new compounds. The use of synthetic organometallic complexes seems to be promising for treatment of malaria infections. Recent progress in identification and development of new drugs promises to lead to a much greater range of antimalarial agents. Organometallic complexes and metalloporphyrins have shown in vitro activity against Plasmodium falciparum. Ferroquine (ferrocenyl chloroquine) is more active than chloroquine against strains and isolates of P. falciparum and shows efficacy against murine parasites.