[
Ann Trop Med Parasitol,
1993]
This paper describes a computer simulation model for onchocerciasis (SIMON). Using epidemiological and entomological data from a specific hyperendemic village in the forest area of Sierra Leone, the model is used to examine the effect of vector and chemotherapeutic control strategies, both separately and in combination, as well as the risk to an uninfected population caused by immigrant, infected Simulium damnosum and humans. The model suggests that, in this village, the human population of about 420 requires an average annual input of about 200 mature fecund, female Onchocerca volvulus per year to maintain a skin-snip prevalence of just under 70%. SIMON also predicts that 99% effective vector control would lead to eradication of all adult worms in 18 years, and that abandoning control before 14 years could lead to recrudescence. Chemotherapy with ivermectin at six-month intervals reaching 90% of eligible persons (effective 66%) might take 29 years to achieve eradication because of continuing transmission, particularly in the early years, but it would probably be possible to abandon treatments after 18 years because the residual worm population would no longer be self-sustaining. Combined ivermectin and vector control, both at reduced levels, could be as effective as 99% vector control. Immigrant infected flies are likely to pose a greater threat to an uninfected human population than small numbers of infected persons. The model suggests that, at levels of infection undetectable by skin-snip, the parasite could linger in the human population for 30 or more years sustained by sporadic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
[
Biochem Soc Trans,
2003]
Despite the central role of the 26 S proteasome in eukaryotic cells, many facets of its structural organization and functioning are still poorly understood. To learn more about the interactions between its different subunits, as well as its possible functional partners in cells, we performed, with Marc Vidal's laboratory (Dana-Farber Cancer Institute, Boston, MA, U.S.A.), a systematic two-hybrid analysis using Caenorhaditis elegans 26 S proteasome subunits as baits (Davy, Bello, Thierry-Mieg, Vaglio, Hitti, Doucette-Stamm, Thierry-Mieg, Reboul, Boulton, Walhout et al. (2001) EMBO Rep. 2, 821-828). A pair-wise matrix of all subunit combinations allowed us to detect numerous possible intra-complex interactions, among which some had already been reported by others and eight were novel. Interestingly, four new interactions were detected between two ATPases of the 19 S regulatory complex and three alpha-subunits of the 20 S proteolytic core. Possibly, these interactions participate in the association of these two complexes to form the 26 S proteasome. Proteasome subunit sequences were also used to screen a cDNA library to identify new interactors of the complex. Among the interactors found, most (58) have no clear connection to the proteasome, and could be either substrates or potential cofactors of this complex. Few interactors (7) could be directly or indirectly linked to proteolysis. The others (12) interacted with more than one proteasome subunit, forming 'interaction clusters' of