Long-term exposure to low 17α-ethinylestradiol (EE2) concentrations disrupts both the reproductive and the immune system of juvenile rainbow trout, Oncorhynchus mykiss.

Estrogenic endocrine disrupting compounds (EEDCs), such as ethinylestradiol (EE2), are well studied for their impact on the reproductive system of fish. EEDCs may also impact the immune system and, as a consequence, the disease susceptibility of fish. It is currently not yet known whether the low concentrations of EEDCs that are able to disrupt the reproductive system of trout are effective in disrupting the immune system and the fish host resistance towards pathogens, too, or whether such immunodisruptive effects would occur only at higher EEDC concentrations. Therefore, in the present study we compare the effect thresholds of low 17α-ethinylestradiol concentrations (1.5 and 5.5 EE2 ng/L) on the reproductive system, the immune system, the energy expenditures and the resistance of juvenile rainbow trout (Oncorhynchus mykiss) against the parasite Tetracapsuloides bryosalmonae - the etiological agent of proliferative kidney disease (PKD) of salmonids. The parasite infection was conducted without injection and under low pathogen exposure concentrations. The disease development was followed over 130 days post infection - in the presence or absence of EE2 exposure. The results show that the long-term EE2 exposure affected, at both concentrations, reproductive parameters like the mRNA levels of hepatic vitellogenin and estrogen receptors. At the same concentrations, EE2 exposure modulated the immune parameters: mRNA levels of several immune genes were altered and the parasite intensity as well as the disease severity (histopathology) were significantly reduced in EE2-exposed fish compared to infected control fish. The combination of EE2 exposure and parasite infection was energetically costly, as indicated by the decreased values of the swim tunnel respirometry. Although further substantiation is needed, our findings suggest that EE2 exerts endocrine disruptive and immunomodulating activities at comparable effect thresholds, since reproductive and immune parameters were affected by the same, low EE2 concentrations.

Catechol pyrazolinones as trypanocidals: fragment-based design, synthesis, and pharmacological evaluation of nanomolar inhibitors of trypanosomal phosphodiesterase B1.

Trypanosomal phosphodiesterases B1 and B2 (TbrPDEB1 and TbrPDEB2) play an important role in the life cycle of Trypanosoma brucei, the causative parasite of human African trypanosomiasis (HAT), also known as African sleeping sickness. We used homology modeling and docking studies to guide fragment growing into the parasite-specific P-pocket in the enzyme binding site. The resulting catechol pyrazolinones act as potent TbrPDEB1 inhibitors with IC50 values down to 49 nM. The compounds also block parasite proliferation (e.g., VUF13525 (20b): T. brucei rhodesiense IC50 = 60 nM, T. brucei brucei IC50 = 520 nM, T. cruzi = 7.6 µM), inducing a typical multiple nuclei and kinetoplast phenotype without being generally cytotoxic. The mode of action of 20b was investigated with recombinantly engineered trypanosomes expressing a cAMP-sensitive FRET sensor, confirming a dose-response related increase of intracellular cAMP levels in trypanosomes. Our findings further validate the TbrPDEB family as antitrypanosomal target.

Nest-mark orientation versus vector navigation in desert ants.

Foraging ants and bees use path-integration vectors and landmark cues for navigation. When in particular experimental paradigms the two types of information--vector-based and landmark-based information--are made to compete with each other, the insect may weight either source more heavily depending on the navigational context and the animal's motivational state. Here we studied the effects of a displaced nest mark on the homing performances of Cataglyphis ants. Foragers were trained to shuttle between the nest, which was marked by a black cylinder (the beacon), and an artificial feeder. Trained ants were captured at the feeder and transferred to a distant test field, where they experienced the nest mark at various positions relative to their home vector. When the beacon was positioned to one side of the point of release, the ants slightly drifted towards the beacon right at the start of their inbound run, but thereafter resumed their home-vector courses. When the nest mark appeared to one side further down the homing course, the ants set off in the home-vector direction, but then gradually drifted towards the beacon. The distance, at which this occurred, and the ants' drift from the home-vector course were very similar across test conditions. During the final search for the nest, landmark information dominated the ants' path integrator. The results clearly show that nest-mark memories are effective during the entire vector-based homeward course, but that they are either only partly activated or partly used unless the state of the ants' path integrator is close to zero.

Trypanosomes and mammalian sperm: one of a kind?

Flagellar-mediated motility is an indispensable function for cell types as evolutionarily distant as mammalian sperm and kinetoplastid parasites, a large group of flagellated protozoa that includes several important human pathogens. Despite the obvious importance of flagellar motility, little is known about the signalling processes that direct the frequency and wave shape of the flagellar beat, or those that provide the motile cell with the necessary environmental cues that enable it to aim its movement. Similarly, the energetics of the flagellar beat and the problem of a sufficient ATP supply along the entire length of the beating flagellum remain to be explored. Recent proteome projects studying the flagella of mammalian sperm and kinetoplastid parasites have provided important information and have indicated a surprising degree of similarities between the flagella of these two cell types.