cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

Differentiation of Bacillus pumilus and Bacillus safensis using MALDI-TOF-MS

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) despite being increasingly used as a method for microbial identification, still present limitations in which concerns the differentiation of closely related species. Bacillus pumillus and Bacillus safensis, are species of biotechnological and pharmaceutical significance, difficult to differentiate by conventional methodologies. In this study, using a well-characterized collection of B. pumillus and B. safensis isolates, we demonstrated the suitability of MALDI-TOF-MS combined with chemometrics to accurately and rapidly identify them. Moreover, characteristic species-specific ion masses were tentatively assigned, using UniProtKB/Swiss-Prot and UniProtKB/TrEMBL databases and primary literature. Delineation of B. pumilus (ions at m/z 5271 and 6122) and B. safensis (ions at m/z 5288, 5568 and 6413) species were supported by a congruent characteristic protein pattern. Moreover, using a chemometric approach, the score plot created by partial least square discriminant analysis (PLSDA) of mass spectra demonstrated the presence of two individualized clusters, each one enclosing isolates belonging to a species-specific spectral group. The generated pool of species-specific proteins comprised mostly ribosomal and SASPs proteins. Therefore, in B. pumilus the specific ion at m/z 5271 was associated with a small acid-soluble spore protein (SASP O) or with 50S protein L35, whereas in B. safensis specific ions at m/z 5288 and 5568 were associated with SASP J and P, respectively, and an ion at m/z 6413 with 50S protein L32. Thus, the resulting unique protein profile combined with chemometric analysis, proved to be valuable tools for B. pumilus and B. safensis discrimination, allowing their reliable, reproducible and rapid identification.Dr. Kasthuri Venkateswaran, Dr. Irene Ouoba, Dr. Joseph W. Kloepper, Dr. Cecilie From and Dr. Maria Morea are gratefully acknowledged for providing isolates FO-36bT, SAFN-027, SAFN-037, KL-052, 51-3C and 82-2C; Bs31; SE 49 (AP3) and SE 52 (AP7); FEL 55, UNG22 and MIL46, respectively. Raquel Branquinho was supported by a PhD fellowship (Ref. SFRH/BD/61410/2009) and Clara Sousa by a post-doctoral fellowship (Ref. SFRH/BPD/70548/2010), from FCT (Fundacao para a Ciencia e Tecnologia, Portugal). Hugo Osorio acknowledges the funding from QREN-FEDER through the Operational Program ON. 2 - O Novo Norte. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by the Portuguese Foundation for Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competin

Applications of MALDI-TOF Mass Spectrometry in Clinical Diagnostic Microbiology

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) represents one of the most accurate, reliable, and fast methods for the identification of bacterial strains from positive cultures, and therefore it has largely replaced all other previously used approaches for microbial identification. The main application of MALDI-TOF MS in clinical microbiology laboratories is the identification of bacteria from colonies recovered from solid culture media. This chapter discusses specific identification procedures that are needed for some bacteria, such as Actinomycetes and Mycobacteria. The performance of MALDI-TOF MS identification relies on the number of mass spectra that reach the quality allowing identification and the number of correct identifications. MALDI-TOF MS has also been proposed for Staphylococcus aureus strain typing or for the detection of biomarkers of the most virulent toxigenic isolates. MALDI-TOF MS could also be used for Mycobacterium

Mise au point d une méthode d identification rapide des corynébactéries du complexe diphtheria par spectrométrie de masse de type MALDI-TOF

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

The Impact of Syria’s Accession to the WTO on Agricultural Sector

This study sets several possible scenarios for Syria's accession to the WTO, and evaluates the impacts of each of them on the farming sector in Syria, focusing on agricultural trade in particular

Réflexions à l'aide d'un cas pratique sur les études de pharmacoépidémiologie à proposer dans le cadre d'un plan de gestion des risques

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

دراسة تأثير إنضمام سوريا لمنظمة التجارة العالمية على القطاع الزراعي

This study sets several possible scenarios for Syria's accession to the WTO, and evaluates the impacts of each of them on the farming sector in Syria, focusing on agricultural trade in particular