The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions

Clinical research is currently exploring the validity of the anti-tumor candidate 3-bromopyruvate (3-BP) as a novel treatment for several types of cancer. However, recent publications have overlooked rarely-cited earlier work about the instability of 3-BP and its decay to 3-hydroxypyruvate (3-HP) which have obvious implications for its mechanism of action against tumors, how it is administered, and for precautions when preparing solutions of 3-BP. This study found the first-order decay rate of 3-BP at physiological temperature and pH has a half-life of only 77 min. Lower buffer pH decreases the decay rate, while choice of buffer and concentration do not affect it. A method for preparing more stable solutions is also reported.     

Cobalamin inactivation induces formyltetrahydrofolate synthetase

Loss of cobalamin function produces profound changes in the metabolism of formate. There is impaired synthesis of formyltetrahydropteroylglutamate synthetase (CHO-H4PteGlu), accumulation of endogenous formate and impaired utilization of [14C]formate. There are contradictory reports on the effect of cobalamin inactivation on CHO-H4PteGlu synthetase. This study confirms a significant increase in synthetase activity following cobalamin inactivation.     

Comparison of the biochemical and kinetic properties of the type 1 receptor tyrosine kinase intracellular domains. Demonstration of differential sensitivity to kinase inhibitors.

Epidermal growth factor receptor (EGFR), ErbB-2, and ErbB-4 are members of the type 1 receptor tyrosine kinase family. Overexpression of these receptors, especially ErbB-2 and EGFR, has been implicated in multiple forms of cancer. Inhibitors of EGFR tyrosine kinase activity are being evaluated clinically for cancer therapy. The potency and selectivity of these inhibitors may affect the efficacy and toxicity of therapy. Here we describe the expression, purification, and biochemical comparison of EGFR, ErbB-2, and ErbB-4 intracellular domains. Despite their high degree of sequence homology, the three enzymes have significantly different catalytic properties and substrate kinetics. For example, the catalytic activity of ErbB-2 is less stable than that of EGFR. ErbB-2 uses ATP-Mg as a substrate inefficiently compared with EGFR and ErbB-4. The three enzymes have very similar substrate preferences for three optimized peptide substrates, but differences in substrate synergies were observed. We have used the biochemical and kinetic parameters determined from these studies to develop an assay system that accurately measures inhibitor potency and selectivity between the type 1 receptor family. We report that the selectivity profile of molecules in the 4-anilinoquinazoline series can be modified through specific aniline substitutions. Moreover, these compounds have activity in whole cells that reflect the potency and selectivity of target inhibition determined with this assay system.     

Pectolytic Clostridium spp. in soils and rhizospheres of carrot and other arable crops in east Scotland

Carrot root tissue discs rotted rapidly in anaerobic conditions after inoculation with soil from 40 different carrot fields and from ten fields of a mixed arable farm. Significant differences occurred in rotting potential between the soils and pectolytic Clostridium spp. were isolated from the rotted discs. Direct counts of pectolytic clostridia on selective pectate plates detected populations of 44–23.5 × 10³ viable propagules/g dry soil in field soils. Significant increases in viable propagules were found in the rhizosphere soils of most carrot crops and in a range of other arable crops examined. The ratios of populations in the rhizospheres and surrounding soils varied between 1.8 and 8.2. Irrigating to excess and inter-row cultivation of carrot crops did not consistently affect populations in soil or on roots.     

The use of barrier-connected pitfall trapping for sampling predatory beetles and spiders

The efficiency of barrier-connected pitfall trapping was compared to conventional single traps or arrays. For ground-active beetles, the use of a pitfall system incorporating a wetting agent with five traps arranged in a cross formation connected by plastic barriers was more efficient than a single dry trap by at least an order of magnitude and at least twice as efficient as five traps without connecting barriers. It is argued that the efficiency of pitfall trapping may be improved markedly by using barrier-connected traps, particularly for some carabid and staphylinid beetles and lycosid spiders. Capture of linyphiids was not improved by the use of barriers and was dependent only on the use of wetting agent and number of traps used.