Cytoplasm Rescues an Arrhythmic Mutant on the Circadian Rhythm of Mating Reactivity in Paramecium bursaria

Cells of an unusual Paramecium bursaria stock (Sj2) expressed rhythmic mating reactivity in a light/dark cycle (LD) and under continuous illumination (LL). When placed in continuous darkness (DD), did not show rhythmicity but rather demonstrated a continuous high mating reactivity. However, mating reactivity was reduced following exposure to a 6-h light pulse interrupting the DD, and then recovered to its former condition. Genetic analysis showed the arrhythmicity in DD to be a dominant character inherited in a Mendelian ratio. On the other hand, a clone (MCIw) that did not show the rhythmicity in either DD or LL was isolated from the parent stock Sj2w following a 5-h treatment with 2 μg/ml nitrosoguanidine (MNNG). The MCIw cells expressed weak rhythmicity in LD, but were insensitive to a 6-h light pulse in DD. The arrhythmicity in LL was inherited cytoplasmically. In addition to this, rhythmicity in LL could be recovered by injection of cytoplasm from the wild-type cell when the recipient cell was homozygous for the wild-type nuclear gene (+/+). The cytoplasmic components or factors are assumed to control the functional circadian system and genetically determine the rhythmicity of mating reactivity.     

Stage Depandent Inhibition of Plasmodiun falcipaium falciparum by Potent Ca2+ and Calmodulin Modulators

The effects Ca2+ channel blockers, verapamil, nicardipine and diltiazem, and of potent calmodulin (CaM) inhibitors, trifluoperazine (TFP), calmidazolium, W-7 and W-5, on Plasmodium falciparum in culture were examined. Among Ca2+ blockers, nicardipine was the most potent with the 50% inhibitory concentration (IC50) of 4.3 μM at 72 h after culture. Parasites were more sensitive to calmidazolium and W-7 with IC50 of 3.4 and 4.5 μM, respectively, than to TFP and W-5. All Ca2+ blockers and CaM inhibitors suppressed parasite development at later stages. Nicardipine, ditiazem, calmidazolium and W-5 also retarded parasite development at earlier stages and/or subsequent growth following pretreatment. Verapamil, nicardipine, TFP and calmidazolium reduced erythocyte invasion by merozoites. Fluroscence microscopy with the cationic flurescent dye rhodamine 123 revealed that nicardipine. TFP and calmidazolium depolarized both the plasma membrane and mitochondrial membrane potentials of the parasite. It is therefore considered that although al Ca2+ and CaM antagonists tested here influence parasite development at later stages, they are multifunctional, having effects not directly associated with Ca2+ channels or CaM.