Electrically-induced mechanical activity of the isolated guinea-pig sciatic nerve. Influences of calcium and anoxia

Summary The electrically induced motility of isolated segments of guinea-pig sciatic nerves is reported. This motility was characterized by waves of tensional variations. The removal of Ca²⁺ from the suspending solution, the addition of EDTA as well as anoxia, resulted in a decrement of tension accompanied by a prolongued duration of the cycles of mechanical activity.This work was supported by grant 6638, from the Consejo Nacional de Investigaciones Cientificas y Técnicas de la República Argentina (C.O.N.I.C.E.T.).     

Increased bilirubin conjugation in the liver and intestinal mucosa of phenobarbital treated rats

Resumen Se estudió el efecto del fenobarbital sobre la conjugación de la bilirrubina en ratas Wistar y Gunn heterocigotas sometidas a la infusión continua de bilirrubina no conjugada. Los resultados obtenidos permiten suponer que el fenobarbital es capaz de estimular la conjugación de la bilirrubina tanto en el hígado como en la mucosa intestinal de ratas con deficiencia parcial de glucuronil transferasa.     

Intrinsic motions along an enzymatic reaction trajectory

The mechanisms by which enzymes achieve extraordinary rate acceleration and specificity have long been of key interest in biochemistry. It is generally recognized that substrate binding coupled to conformational changes of the substrate-enzyme complex aligns the reactive groups in an optimal environment for efficient chemistry. Although chemical mechanisms have been elucidated for many enzymes, the question of how enzymes achieve the catalytically competent state has only recently become approachable by experiment and computation. Here we show crystallographic evidence for conformational substates along the trajectory towards the catalytically competent 'closed' state in the ligand-free form of the enzyme adenylate kinase. Molecular dynamics simulations indicate that these partially closed conformations are sampled in nanoseconds, whereas nuclear magnetic resonance and single-molecule fluorescence resonance energy transfer reveal rare sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale. Thus, the larger-scale motions in substrate-free adenylate kinase are not random, but preferentially follow the pathways that create the configuration capable of proficient chemistry. Such preferred directionality, encoded in the fold, may contribute to catalysis in many enzymes.     

The common biology of cancer and ageing

At first glance, cancer and ageing would seem to be unlikely bedfellows. Yet the origins for this improbable union can actually be traced back to a sequence of tragic--and some say unethical--events that unfolded more than half a century ago. Here we review the series of key observations that has led to a complex but growing convergence between our understanding of the biology of ageing and the mechanisms that underlie cancer.