Population genetics of Trypanosoma brucei circulating in Glossina palpalis palpalis and domestic animals of the Fontem sleeping sickness focus of Cameroon

BACKGROUND: Human African Trypanosomiasis is still a public health threat in Cameroon. To assess Trypanosoma brucei strains circulating in the Fontem sleeping sickness focus, we conducted a genetic structure study using microsatellites to assess genotypes circulating in both tsetse flies and domestic animals. METHOD: For this study, pyramidal traps were set up and 2695 tsetse flies were collected and 1535 (57%) living flies were dissected and their mid-guts collected. Furthermore, blood samples were collected from 397 domestic animals (pigs, goats, sheep and dogs). DNA was extracted from midguts and blood samples, and specific primers were used to identify trypanosomes of the subgenus Trypanozoon. All positive samples were genetically characterized with seven microsatellite markers. RESULTS: Seventy five (4.7%) midguts of tsetse flies and 140 (35.2%) domestic animals were found infected by trypanosomes of the subgenus Trypanozoon. The genetic characterization of 215 Trypanozoon positive samples (75 from tsetse and 140 from animals) revealed a genetic diversity between Trypanosoma brucei circulating in tsetse and domestic animals. Of these positive samples, 87 (40.5%) single infections were used here to investigate the population genetics of Trypanosoma brucei circulating in tsetse and domestic animals. The dendrogram illustrating the genetic similarities between Trypanosoma brucei genotypes was subdivided into four clusters. The samples from tsetse belonged to the same cluster whereas the samples from domestic animals and espcially pigs were distributed in the four clusters. CONCLUSION: Pigs appeared as the animal species harboring the highest number of different Trypanosoma brucei strains. They may play an important role in the propagation of different genotypes. The F(ST) values revealed a sub structuration of Trypanosoma brucei according to hosts and sometimes villages. The data obtained from this study may have considerable importance for the understanding of the transmission and the spread of specific genotypes of Trypanosoma brucei

Excreted/Secreted Proteins from Trypanosome Procyclic Strains

Trypanosoma secretome was shown to be involved in parasite virulence and is suspected of interfering in parasite life-cycle steps such as establishment in the Glossina midgut, metacyclogenesis. Therefore, we attempted to identify the proteins secreted by procyclic strains of T. brucei gambiense and T. brucei brucei, responsible for human and animal trypanosomiasis, respectively. Using mass spectrometry, 427 and 483 nonredundant proteins were characterized in T. brucei brucei and T. brucei gambiense secretomes, respectively; 35% and 42% of the corresponding secretome proteins were specifically secreted by T. brucei brucei and T. brucei gambiense, respectively, while 279 proteins were common to both subspecies. The proteins were assigned to 12 functional classes. Special attention was paid to the most abundant proteases (14 families) because of their potential implication in the infection process and nutrient supply. The presence of proteins usually secreted via an exosome pathway suggests that this type of process is involved in trypanosome ESP secretion. The overall results provide leads for further research to develop novel tools for blocking trypanosome transmission

Intertwining threshold settings, biological data and database knowledge to optimize the selection of differentially expressed genes from microarray.

International audienceBACKGROUND: Many tools used to analyze microarrays in different conditions have been described. However, the integration of deregulated genes within coherent metabolic pathways is lacking. Currently no objective selection criterion based on biological functions exists to determine a threshold demonstrating that a gene is indeed differentially expressed. METHODOLOGY/PRINCIPAL FINDINGS: To improve transcriptomic analysis of microarrays, we propose a new statistical approach that takes into account biological parameters. We present an iterative method to optimise the selection of differentially expressed genes in two experimental conditions. The stringency level of gene selection was associated simultaneously with the p-value of expression variation and the occurrence rate parameter associated with the percentage of donors whose transcriptomic profile is similar. Our method intertwines stringency level settings, biological data and a knowledge database to highlight molecular interactions using networks and pathways. Analysis performed during iterations helped us to select the optimal threshold required for the most pertinent selection of differentially expressed genes. CONCLUSIONS/SIGNIFICANCE: We have applied this approach to the well documented mechanism of human macrophage response to lipopolysaccharide stimulation. We thus verified that our method was able to determine with the highest degree of accuracy the best threshold for selecting genes that are truly differentially expressed

Human African Trypanosomiasis Transmission, Kinshasa, Democratic Republic of Congo

To investigate the epidemiology of human African trypanosomiasis (sleeping sickness) in Kinshasa, Democratic Republic of Congo, 2 entomologic surveys were conducted in 2005. Trypanosoma brucei gambiense and human-blood meals were found in tsetse fly midguts, which suggested active disease transmission. Vector control should be used to improve human African trypanosomiasis control efforts

Physiopathology of somatolactotroph cells: from transduction mechanisms to cotargeting therapy.

International audienceIn pituitary somatolactotroph cells, G protein-coupled receptors and receptor tyrosine kinases binding their specific ligands trigger an enzymatic cascade that converges to MAP kinase activation in the subcellular compartment. Different signaling pathways, such as AC/cAMP/PKA and PI3K/Akt pathways, interact with MAP kinase to regulate key physiological functions, such as hormonal secretion and cell proliferation. Abnormalities affecting these signaling pathways have been identified as preponderant factors of pituitary tumorigenesis. In addition to trans-sphenoidal surgery, somatostatin analogs are used to control hormonal hypersecretion in GH-secreting adenomas. However, a subset of these tumors remains uncontrolled with these treatFments, calling for new therapeutic approaches. In these cases, novel multivalent somatostatin analogs or new somatostatin-dopamine chimeric molecules could be of interest. Another attractive therapeutic approach may be to use one or several inhibitors acting downstream in the signaling pathway, such as mammalian target of rapamycin inhibitor. Cotargeting therapy and gene therapy are promising tools for these problematic pituitary tumors

The mosaic genome of warm-blooded vertebrates

7 p.-5 fig.-1 tab.Most of the nuclear genome of warm-blooded vertebrates is a mosaic of very long (>>200 kilobases) DNA segments, the isochores; these isochores are fairly homogeneous in base composition and belong to a small number of major classes distinguished by differences in guanine-cytosine (GC) content. The families of DNA molecules derived from such classes can be separated and used to study the genome distribution of any sequence which can be probed. This approach has revealed (i) that the distribution of genes, integrated viral sequences, and interspersed repeats is highly nonuniform in the genome, and (ii) that the base composition and ratio of CpG to GpC in both coding and noncoding sequences, as well as codon usage, mainly depend on the GC content of the isochores harboring the sequences. The compositional compartmentalization of the genome of warm-blooded vertebrates is discussed with respect to its evolutionary origin, its causes, and its effects on chromosome structure and function.Peer reviewe