Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target.

The three human SNM1 metallo-β-lactamase fold nucleases (SNM1A-C) play key roles in DNA damage repair and in maintaining telomere integrity. Genetic studies indicate that they are attractive targets for cancer treatment and to potentiate chemo- and radiation-therapy. A high-throughput screen for SNM1A inhibitors identified diverse pharmacophores, some of which were shown by crystallography to coordinate to the di-metal ion centre at the SNM1A active site.

Discovery and characterization of novel TRPML1 agonists.

Screening a library of >100,000 compounds identified the substituted tetrazole compound 1 as a selective TRPML1 agonist. Both enantiomers of compound 1 were separated and profiled in vitro and in vivo. Their selectivity, ready availability and CNS penetration should enable them to serve as the tool compounds of choice in future TRPML1 channel activation studies.

Portal and Mesenteric Vein Thrombosis Associated with Decompression Sickness in a 48-Year-Old Deep Sea Self-Contained Underwater Breathing Apparatus (SCUBA) Diver.

BACKGROUND Deep sea diving can cause decompression illness which comprises both decompression sickness and arterial gas embolism. Decompression sickness is a clinical diagnosis with symptoms including dizziness, joint pain, rash, and myalgias and is due to nitrogen bubbles that form in tissues during ascent. These gas bubbles can be clinically silent even in the absence of decompression sickness and can rarely predispose a patient to venous thrombus, for which the role of hyperbaric oxygen (HBO) is undefined.

A high-throughput screen for the identification of compounds that inhibit nematode gene expression by targeting spliced leader trans-splicing.

Infections with parasitic nematodes are among the most significant of the neglected tropical diseases affecting about a billion people living mainly in tropical regions with low economic activity. The most effective current strategy to control nematode infections involves large scale treatment programs with anthelmintic drugs. This strategy is at risk from the emergence of drug resistant parasites.