Endochin-like quinolones (ELQs) and bumped kinase inhibitors (BKIs): Synergistic and additive effects of combined treatments against Neospora caninum infection in vitro and in vivo.

The apicomplexan parasite Neospora caninum is an important causative agent of congenital neosporosis, resulting in abortion, birth of weak offspring and neuromuscular disorders in cattle, sheep, and many other species. Among several compound classes that are currently being developed, two have been reported to limit the effects of congenital neosporosis: (i) bumped kinase inhibitors (BKIs) target calcium dependent protein kinase 1 (CDPK1), an enzyme that is encoded by an apicoplast-derived gene and found only in apicomplexans and plants. CDPK1 is essential for host cell invasion and egress; (ii) endochin-like quinolones (ELQs) are inhibitors of the cytochrome bc complex of the mitochondrial electron transport chain and thus inhibit oxidative phosphorylation.

Experimental demonstration of a 4,294,967,296-QAM-based Y-00 quantum stream cipher template carrying 160-Gb/s 16-QAM signals.

We demonstrate a 4,294,967,296-quadrature amplitude modulation (QAM) based Y-00 quantum stream cipher system carrying a 160-Gb/s 16-QAM signal transmitted over 320-km SSMF. The ultra-dense QAM cipher template is realized by an integrated two-segment silicon photonics I/Q modulator.

One health therapeutics: Target-Based drug development for cryptosporidiosis and other apicomplexa diseases.

This is a review of the development of bumped-kinase inhibitors (BKIs) for the therapy of One Health parasitic apicomplexan diseases. Many apicomplexan infections are shared between humans and livestock, such as cryptosporidiosis and toxoplasmosis, as well as livestock only diseases such as neosporosis. We have demonstrated proof-of-concept for BKI therapy in livestock models of cryptosporidiosis (newborn calves infected with Cryptosporidium parvum), toxoplasmosis (pregnant sheep infected with Toxoplasma gondii), and neosporosis (pregnant sheep infected with Neospora caninum).

The Impact of BKI-1294 Therapy in Mice Infected With the Apicomplexan Parasite and Re-infected During Pregnancy.

Exposure of tachyzoites to BKI-1294 results in the formation of long-lived multinucleated complexes (MNCs). However, treatment of BALB/c mice with BKI-1294 shortly after infection during pregnancy was safe and profoundly reduced pup mortality and vertical transmission. We hypothesized that the formation of MNCs could trigger immune responses that contribute to BKI efficacy .