Strong poison revisited

Selenium in the form of selenocysteine plays an essential role in a number of proteins, but its role in non-enzymatic biochemistry is also important. In this short review we discuss the interactions between inorganic selenium, arsenic and mercury under physiological conditions, especially in the presence of glutathione. This chemistry is obviously important in making the arsenic and mercury unavailable for more toxic interactions, but in the process it suggests that a side-effect of chronic arsenic and/or mercury exposure is likely to be functional selenium deficiency.     

An ice-binding protein from an Antarctic sea ice bacterium

An Antarctic sea ice bacterium of the Gram-negative genus Colwellia, strain SLW05, produces an extracellular substance that changes the morphology of growing ice. The active substance was identified as a approximately 25-kDa protein that was purified through its affinity for ice. The full gene sequence was determined and was found to encode a 253-amino acid protein with a calculated molecular mass of 26,350 Da. The predicted amino acid sequence is similar to predicted sequences of ice-binding proteins recently found in two species of sea ice diatoms and a species of snow mold. A recombinant ice-binding protein showed ice-binding activity and ice recrystallization inhibition activity. The protein is much smaller than bacterial ice-nucleating proteins and antifreeze proteins that have been previously described. The function of the protein is unknown but it may act as an ice recrystallization inhibitor to protect membranes in the frozen state.     

Juxtacrine activation of EGFR regulates claudin expression and increases transepithelial resistance

Heparin-binding (HB)-EGF, a ligand for EGF receptors, is synthesized as a membrane-anchored precursor that is potentially capable of juxtacrine activation of EGF receptors. However, the physiological importance of such juxtacrine signaling remains poorly described, due to frequent inability to distinguish effects mediated by membrane-anchored HB-EGF vs. mature "secreted HB-EGF." In our studies, using stable expression of a noncleavable, membrane-anchored rat HB-EGF isoform (MDCK(rat5aa) cells) in Madin-Darby canine kidney (MDCK) II cells, we observed a significant increase in transepithelial resistance (TER). Similar significant increases in TER were observed on stable expression of an analogous, noncleavable, membrane-anchored human HB-EGF construct (MDCK(human5aa) cells). The presence of noncleavable, membrane-anchored HB-EGF led to alterations in the expression of selected claudin family members, including a marked decrease in claudin-2 in MDCK(rat5aa) cells compared with the control MDCK cells. Reexpression of claudin-2 in MDCK(rat5aa) cells largely prevented the increases in TER. Ion substitution studies indicated decreased paracellular ionic permeability of Na(+) in MDCK(rat5aa) cells, further indicating that the altered claudin-2 expression mediated the increased TER seen in these cells. In a Ca(2+)-switch model, increased phosphorylation of EGF receptor and Akt was observed in MDCK(rat5aa) cells compared with the control MDCK cells, and inhibition of these pathways inhibited TER changes specifically in MDCK(rat5aa) cells. Therefore, we hypothesize that juxtacrine activation of EGFR by membrane-anchored HB-EGF may play an important role in the regulation of tight junction proteins and TER.     

2-Aryl benzimidazoles featuring alkyl-linked pendant alcohols and amines as inhibitors of checkpoint kinase Chk2

A series of benzimidazole compounds containing pendant alcohol and amine moieties was found to be active against checkpoint kinase Chk2. These compounds were prepared to examine a potential hydrogen bond interaction with an active site residue and to investigate replacement of a biaryl linker with an aliphatic system in an effort to improve solubility.     

A scorpion neurotoxin increases the potency of a fungal insecticide

The low virulence of the insecticidal fungus Metarhizium anisopliae has stymied its widespread use in controlling insect pests. We show that high-level expression of an insect-specific neurotoxin from the scorpion Androctonus australis in hemolymph by M. anisopliae increases fungal toxicity 22-fold against tobacco hornworm (Manduca sexta) caterpillars and ninefold against adult yellow fever mosquitoes (Aedes aegypti) without compromising host specificity. Prelethal effects include reduced mobility and feeding of the insects targeted.