On the trail of Dr. Fifer.

A gift from a patient drew Hope, BC, family physician Gerd Asche irrevocably into the local medical history of the 1858 Fraser River Gold Rush. Because of his interest in Dr. Max William Fifer, Asche undertook research missions in British Columbia, England and the US, converted his computer room to a research and writing centre, and wrote a biography of his predecessor and colleague. He recounts his experience and the growing satisfaction provided by his interest in medical history.     

Multiple Molecular Mechanisms Cause Reproductive Isolation between Three Yeast Species

Nuclear-mitochondrial conflict (cytonuclear incompatibility) is a specific form of Dobzhansky-Muller incompatibility previously shown to cause reproductive isolation in two yeast species. Here, we identified two new incompatible genes, MRS1 and AIM22, through a systematic study of F2 hybrid sterility caused by cytonuclear incompatibility in three closely related Saccharomyces species (S. cerevisiae, S. paradoxus, and S. bayanus). Mrs1 is a nuclear gene product required for splicing specific introns in the mitochondrial COX1, and Aim22 is a ligase encoded in the nucleus that is required for mitochondrial protein lipoylation. By comparing different species, our result suggests that the functional changes in MRS1 are a result of coevolution with changes in the COX1 introns. Further molecular analyses demonstrate that three nonsynonymous mutations are responsible for the functional differences of Mrs1 between these species. Functional complementation assays to determine when these incompatible genes altered their functions show a strong correlation between the sequence-based phylogeny and the evolution of cytonuclear incompatibility. Our results suggest that nuclear-mitochondrial incompatibility may represent a general mechanism of reproductive isolation during yeast evolution.     

Parallelism between ethanol and imidazole interactions with horse liver alcohol dehydrogenase

The rate effects of imidazole on the EE isoenzyme of horse liver alcohol dehydrogenase have been analysed in terms of the elucidated kinetic mechanism of the enzyme. These imidazole effects on both directions of the reaction within nonexcess as well as excess ranges of substrate concentrations pointed to the competition between imidazole and ethanol for binding to the same three enzyme species in the kinetic mechanism, namely the free enzyme, the enzyme-NAD+ complex, and the enzyme-NADH complex. Moreover, both imidazole and ethanol brought about an enhancement in the rate of dissociation of NAD+ from its binding site on the enzyme.     

Plant Desiccation and Protein Synthesis: II. On the Relationship between Endogenous Adenosine Triphosphate Levels and Protein-synthesizing Capacity

Rehydration of Tortula ruralis in 2,4-dinitrophenol inhibits protein synthesis, polysome formation, and ATP production. Polysomes are conserved intact and are active in vitro in hydrated Tortula placed in this chemical, although in vivo protein synthesis is inhibited. Hydrated moss placed under nitrogen in the dark shows a reduced capacity for ATP and protein synthesis, but polysomes are conserved. During anaerobiosis in light, ATP and protein synthesis are unaffected. Rehydration of slow-dried Tortula in nitrogen in the dark results in reduced in vivo protein synthesis, but not polysome formation; this reduction is much less in the light. Slow-dried moss, but not fast-dried, has a greatly reduced ATP content in the dry state, but this rapidly returns to normal levels on rehydration. The prolonged burst in respiration observed previously on rehydration of Tortula is not paralleled by ATP accumulation. Changes in energy charge in all treatments tested follow the changes in ATP. The aquatic moss, Hygrohypnum luridum, which is intolerant to drought, loses ATP during fast drying and this is not replenished on subsequent rehydration.     

Catalytic antibodies: balancing between Dr. Jekyll and Mr. Hyde

The immunoglobulin molecule is a perfect template for the de novo generation of biocatalytic functions. Catalytic antibodies, or abzymes, obtained by the structural mimicking of enzyme active sites have been shown to catalyze numerous chemical reactions. Natural enzyme analogs for some of these reactions have not yet been found or possibly do not exist at all. Nowadays, the dramatic breakthrough in antibody engineering and expression technologies has promoted a considerable expansion of immunoglobulin's medical applications and is offering abzymes a unique chance to become a promising source of high‐precision “catalytic vaccines.” At the same time, the discovery of natural abzymes on the background of autoimmune disease revealed their beneficial and pathogenic roles in the disease progression. Thus, the conflicting Dr. Jekyll and Mr. Hyde protective and destructive essences of catalytic antibodies should be carefully considered in the development of therapeutic abzyme applications.