Search

Apicomplexa encompasses a large number of intracellular parasites infecting a wide range of animals. Cyclic nucleotide signaling is crucial for a variety of apicomplexan life stages and cellular processes. The cyclases and kinases that synthesize and respond to cyclic nucleotides (i.e., 3',5'-cyclic guanosine monophosphate and 3',5'-cyclic adenosine monophosphate) are highly conserved and essential throughout the parasite phylum. Growing evidence indicates that phosphodiesterases (PDEs) are also critical for regulating cyclic nucleotide signaling via cyclic nucleotide hydrolysis. Here, we discuss recent advances in apicomplexan PDE biology and opportunities for therapeutic interventions, with special emphasis on the major human apicomplexan parasite genera Plasmodium , Toxoplasma , Cryptosporidium , and Babesia . In particular, we show a highly flexible repertoire of apicomplexan PDEs associated with a wide range of cellular requirements across parasites and lifecycle stages. Despite this phylogenetic diversity, cellular requirements of apicomplexan PDEs for motility, host cell egress, or invasion are conserved. However, the molecular wiring of associated PDEs is extremely malleable suggesting that PDE diversity and redundancy are key for the optimization of cyclic nucleotide turnover to respond to the various environments encountered by each parasite and life stage. Understanding how apicomplexan PDEs are regulated and integrating multiple signaling systems into a unified response represent an untapped avenue for future exploration., Competing Interests: The authors declare no conflict of interest.

The M(w) = 8.3 deep (636 kilometers) Bolivian earthquake of 9 June 1994 was the largest deep-focus earthquake ever recorded. Seismic data from permanent stations plus portable instruments in South America show that rupture occurred on a horizontal plane and extended at least 30 by 50 kilometers. Rupture proceeded at 1 to 3 kilometers per second along the down-dip azimuth of the slab and penetrated through more than a third of the slab thickness. This extent is more than three times that expected for a metastable wedge of olivine at the core of the slab, and thus appears to be incompatible with an origin by transformational faulting. These large events may instead represent slip on preserved zones of weakness established in oceanic lithosphere at the Earth's surface.

A number of commercially available optical coatings, both antireflective and high reflective, have been tested for their laser-induced damage threshold, involving a total of eight different laboratories. The results obtained and the experimental methods used at these laboratories were discussed among the participants in this round robin at a minisymposium held at Balzers, Liechtenstein, 9-10 Dec. 1982. A final report of the round robin and a summary of the conclusions drawn at that symposium are presented.