1-Methyl-1-pyrazole-5-carboxamide Derivatives Exhibit Unexpected Acute Mammalian Toxicity.

A series of 1-methyl-1-pyrazole-5-carboxamides were synthesized as potent inhibitors of the parasitic nematode of sheep, . These compounds did not show overt cytotoxicity to a range of mammalian cell lines under standard in vitro culture conditions, had high selectivity indices, and were progressed to an acute toxicity study in a rodent model. Strikingly, acute toxicity was observed in mice.

Human Aurora kinase inhibitor Hesperadin reveals epistatic interaction between Plasmodium falciparum PfArk1 and PfNek1 kinases.

Mitosis has been validated by numerous anti-cancer drugs as being a druggable process, and selective inhibition of parasite proliferation provides an obvious opportunity for therapeutic intervention against malaria. Mitosis is controlled through the interplay between several protein kinases and phosphatases. We show here that inhibitors of human mitotic kinases belonging to the Aurora family inhibit P.

Evaluation of the productive characteristics of the Caqueteño Creole cattle breed.

The objective of this research was to evaluate the productive and reproductive characteristics of the Caqueteño Creole cattle breed. Data was taken from 655 animals organized into 6 groups: group 1 (n = 185), pure Caqueteño Creole cattle breed (Caqueteño); group 2 (n = 34), Caqueteño Creole cattle breed crossing for multiracial animals (Caqueteño 50% × multiracial 50%); group 3 (n = 10) (Caqueteño 75% × Bos indicus 25%); group 4 (n = 56), crossbreed F1 (Bos taurus × B. indicus); group 5 (n = 168), animals with B.

Interaction of Plasmodium falciparum casein kinase 1 with components of host cell protein trafficking machinery.

A pool of Plasmodium falciparum casein kinase 1 (PfCK1) has been shown to localize to the host red blood cell (RBC) membrane and be secreted to the extracellular medium during trophozoite stage of development. We attempted to identify mechanisms for secretion of PfCK1 and its appearance on the RBC membrane. We found that two host proteins with established functions in membrane trafficking in higher eukaryotes, GTPase-activating protein and Vps9 domain-containing protein 1 (GAPVD1), and Sorting nexin 22, consistently co-purify with PfCK1, suggesting that the parasite utilizes trafficking pathways previously thought to be inactive in RBCs.

Synthetic Kavalactone Analogues with Increased Potency and Selective Anthelmintic Activity against Larvae of In Vitro.

Kava extract, an aqueous rhizome emulsion of the plant , has been used for centuries by Pacific Islanders as a ceremonial beverage, and has been sold as an anxiolytic agent for some decades. Kavalactones are a major constituent of kava extract. In a previous investigation, we had identified three kavalactones that inhibit larval development of in an in vitro-bioassay.