Advances in Biophysics最新文献

The phylogenetic relationships of the carabid ground beetles have been estimated by analysing a large part of the ND5 gene sequences of more than 1,000 specimens consisting of the representative species and geographic races covering most of the genera and subgenera known in the world. From the phylogenetic analyses in conjunction with the mtDNA-based dating, a scenario of the establishment of the present habitats of the respective Japanese carabids has been constructed.

The carabid diversification took place ca. 40 MYA as an explosive radiation of the major genera. During evolution, occasional small or single bangs also took place, sometimes accompanied by parallel morphological evolution in phylogenetically remote as well as close lineages. The existence of silent periods, in which few morphological changes took place, has been recognized during evolution. Thus, the carabid evolution is discontinuous, alternatively having a phase of rapid morphological change and a silent phase.

The isolation of ATP synthase (F₀F₁) (82) and F₀ (83) 34 years ago finally revealed that F₀F₁ is a motor composed of F₀ (ion-motor, abc subunits) and F₁ (ATP-motor, α₃β₃γδε subunits) (Fig. 1). The single molecule videotape (4, 5, 65, 66) revealed that γε axis of F₁ rotates counterclockwise, proceeds by each $\text{2π}\text{3}$ step, and is driven by torque of 42 pN·nm (12) with nearly 100% efficiency (5) (Fig. 4). The motor is composed of a rotor (γε-F₀-c) and a stator (α₃β₃δ-F₀-ab), and the rotor is connected to a shaft (γε). Since F₀F₁ is driven by Δ$\text{̄}$gmH⁺ (9, 10, 84), biophysical studies on stable TF₀F₁ (1, 7) are essential to elucidate the mechanism. These include nanomechanics (4, 5) (Fig. 4), crystallography (2, 3) (Figs. 2 and 3), NMR (51, 52), ESR (56), synchrotron analysis (3, 28), and electrophysiology (10, 25). The K_mATP value of rotation is 0.8 μm, with the V_max of 3.9 rps (5). This corresponds to the bi-site catalysis in proton transport by F₀F₁ (10, 70, 84). X-ray crystallography of MF₁ (2) and the α₃β₃ oligomer of TF₁ (3) (Fig. 2) together with mutation analyses revealed the role of residues in the rotation. The idea of elastic energy store is proposed in α₃β₃γ during the stepping time (up to a few sec) after the ATP binding. Biological studies have partially clarified the genetic and kinetic regulation of the rotation in MF₁. Both theories (6, 7, 62, 64, 85) and the biological significance (17) of the intramolecular rotation of F₀F₁ await further studies, especially those of F₀ and minor subunits.

Elucidation of interrelationships among sequence, structure, function, and evolution (FESS relationships) of a family of genes or gene products is a central theme of modern molecular biology. Multiple sequence alignment has been proven to be a powerful tool for many fields of studies such as phylogenetic reconstruction, illumination of functionally important regions, and prediction of higher order structures of proteins and RNAs. However, it is far too trivial to automatically construct a multiple alignment from a set of related sequences. A variety of methods for solving this computationally difficult problem are reviewed. Several important applications of multiple alignment for elucidation of the FESS relationships are also discussed.

For a long period, progressive methods have been the only practical means to solve a multiple alignment problem of appreciable size. This situation is now changing with the development of new techniques including several classes of iterative methods. Today's progress in multiple sequence alignment methods has been made by the multidisciplinary endeavors of mathematicians, computer scientists, and biologists in various fields including biophysicists in particular. The ideas are also originated from various backgrounds, pure algorithmics, statistics, thermodynamics, and others. The outcomes are now enjoyed by researchers in many fields of biological sciences.

In the near future, generalized multiple alignment may play a central role in studies of FESS relationships. The organized mixture of knowledge from multiple fields will ferment to develop fruitful results which would be hard to obtain within each area. I hope this review provides a useful information resource for future development of theory and practice in this rapidly expanding area of bioinformatics.

Three genomically distinct isoforms of RyR are now known. RyR1 homologue is the primary isoform in skeletal muscles, whereas in cardiac muscles it is RyR2 homologue. RyR3 homologue occurs ubiquitously in many cells, but the biological function is little known, partly because of its minuscule amount in mammalian cells. The difference among RyR isoforms may not be so great in CICR activity, in other words, in the interaction of RyR isoforms with Ca²⁺, adenine nucleotides and caffeine. Species specificity among RyR1 homologues may be more important in the apparent difference between RyR1 and RyR3 homologues. CICR is likely to be the dominant underlying mechanism for E-C coupling in the cardiac muscle and probably in cells other than the skeletal muscle where the significance of CICR is controversial in physiological contraction. In E-C coupling of skeletal muscle (DICR), the reciprocal tight interactions between DHPR and RyR1 are critically required. The α₁ subunit of DHPR was only the main target of our current interests in the interaction with RyR1; the involvement of auxiliary subunits of $\text{α}{}_2\text{δ}$ and β subunits and their mutual interactions, however, are also important. DICR and CICR in RyR1 share common properties of stimulation by concentrated solutes and modulation by luminal calcium or Ca²⁺, suggesting that the main difference between the two Ca²⁺ release mechanisms may be in the gating mechanism of the channel. Further investigations are required to understand molecular interactions during E-C coupling.