The orderly progression of mitosis depends on the formation and proper functioning of the division machinery called mitotic spindles. The major framework of the spindle is microtubules, whose temporal and spatial distribution is controlled by centrosomes (MTOCs: microtubuleorganizing centers) located at each spindle pole. Recent advance in biochemical, immunological and genetic analysis of mitotic cells has allowed us to identify a variety of molecules associated with centrosomes in mitotic cells. An attempt has been made to summarize the current knowledge on the centrosomal components, that should be important for understanding the molecular basis of mitosis and its regulation.
One of the best methods for understanding the forces responsible for holding proteins in their highly cooperative structure is to study effects of amino acid replacements on thermal unfolding of proteins using high sensitivity differential scanning calorimetry (DSC). This article outlines examples of the DSC study on the effects of mutations of T4 phage lysozyme and staphylococcal nuclease.
Recent development of three-dimensional (3D) nuclear magnetic resonance (NMR) spectroscopy offers a new sight into the determination of the structures of larger proteins by increasing spectral resolution in three frequency axes. Simultaneously, problems of sensitivity loss due to larger linewidths associated with the increase of molecular weights has been solved by use of large three-dimensional NMR/protein structure/triple-resonance NMR/stable isotope
Protein friction is generated by the "reversible" interaction between a protein motor and its corresponding cytofilament when there is a relative movement between them. The protein friction is proportional to the sliding velocity and>x10 of solvent friction. A protein friction model is explained. The model is consistent with the characteristics of the in vitro sliding movement induced by protein motors, including the velocity-limiting mechanism, and those of the Brownian movement of cytofilaments induced by the motors. The model implies possible involvement of thermal fluctuations of the motor protein-structure in the mechanism of the sliding force generation, which is coupled with the cytofilament-activated ATP hydrolysis by the motors.
In order to elucidate the energetics of RNA cleaving reactions, the reaction coordinate was simulated by ab initio molecular orbital calculations. The calculated energy profile was applied to explain mutagenesis results of RNase T1 and Barnase in which acids/bases play pivotal roles in catalysis. Enzyme kinetics were also analyzed in some detail putting emphasis on slopes in pH-rate profiles. Further calculations invotving Mg2+ reveal that, in ribozyme reactions, the actual catalyst may be Mg2+ and the RNA components may merely provide the proper binding site for the Mg2+ ion.
Substantial proportions of neuronal cells composing many loci in the nervous system are destined to die at the terminal stage of the ontogeny. Molecular mechanisms of the programmed cell death have been analyzed principally in view of accessibility to neurotrophic factors. I propose here a possible mechanism that killer proteins such as NBCF induced upon shortage of neurotrophic factors at the cell death period counteract direct cytoprotective effects of anti-killer factors associated with neurodifferentiation and bring about programmed cell death of neurons whose nerve endings are insufficiently multibranched.
Mathematical models have contributed toward understanding the mechanisms of human circadian system. Results given by those models could qualitatively simulate some of features of the circadian system, but were difficult to be interpreted at physiological level. We have developed a quantitative model of human sleep-waking behavior based on a hypothesis that NREMS (Non Rapid Eye Movement Sleep) is controlled by thermoregulatory mechanisms of the preoptic/anterior hypothalamus, which is supported by recent observations. Circadian and homeostatic thermoregulatory processes may be integrated in this brain area. Simulations under entrained conditions show that the model closely mimics typical features of human sleep-wake rhythms. Simultaneously, the model couuld predict the possible underlying mechanisms for those features. These results suggest that the control of sleep-waking cycle can be understood within the framework of thermoregulation.
Barn owls localize sound most accurately among all animals. Studies on the brain mechanisms of their sound localization represent a case where many important questions in sensory physiology can be addressed in a straightforward way. This article will review our current understanding of how neurons in the owl's auditory system create their selectivity to position of sounds.