A mechanism for early branching in lung morphogenesis

The lung is a highly branched fluid-filled structure, that develops by repeated dichotomous branching of a single bud off the foregut, of epithelium invaginating into mesenchyme. Incorporating the known stress response of developing lung tissues, we model the developing embryonic lung in fluid mechanical terms. We suggest that the repeated branching of the early embryonic lung can be understood as the natural physical consequence of the interactions of two or more plastic substances with surface tension between them. The model makes qualitative and quantitative predictions, as well as suggesting an explanation for such observed phenomena as the asymmetric second branching of the embryonic bronchi.     

Turing bifurcations with a temporally varying diffusion coefficient

This paper is concerned with the possibility of Turing bifurcations in a reaction-diffusion system in which the diffusion coefficient of one species varies periodically in time. This problem was introduced and investigated numerically by Timm and Okubo (J. Math. Biol. 30, 307, 1992) in the context of predator-prey interactions in plankton populations. Here, I consider the simple case in which the temporal variation in diffusivity has a square-tooth form, alternating between two constant values, with a period that is long compared with the time scale of the kinetics. The analysis is valid for any set of reaction kinetics. I derive explicit expressions for the Floquet multipliers that determine the stability of the steady state, and thereby obtain the conditions for diffusion driven instability to occur. These conditions imply that, depending on the kinetics, the homogeneous equilibrium may be either more or less stable than when the diffusion coefficient is a constant equal to the mean of the variable diffusivity. I go on to consider the form of the solution when diffusion driven instability does occur, and I use perturbation theory to determine the effect of a small temporal variation in the diffusion coefficient on the spatial wavelength of the pattern that results from diffusion driven instability.     

Atomic and residue hydrophilicity in the context of folded protein structures

Water-protein interactions drive protein folding, stabilize the folded structure, and influence molecular recognition and catalysis. We analyzed the closest protein contacts of 10,837 water molecules in crystallographic structures to define a specific hydrophilicity scale reflecting specific rather than bulk solvent interactions. The tendencies of different atom and residue types to be the nearest protein neighbors of bound water molecules correlated with other hydrophobicity scales, verified the relevance of crystallographically determined water positions, and provided a direct experimental measure of water affinity in the context of the folded protein. This specific hydrophilicity was highly correlated with hydrogen-bonding capacity, and correlated better with experimental than computationally derived measures of partitioning between aqueous and organic phases. Atoms with related chemistry clustered with respect to the number of bound water molecules. Neutral and negatively charged oxygen atoms were the most hydrophilic, followed by positively-charged then neutral nitrogen atoms, followed by carbon and sulfur atoms. Agreement between observed side-chain specific hydrophilicity values and values derived from the atomic hydrophilicity scale showed that hydrophilicity values can be synthesized for different functional groups, such as unusual side or main chains, discontinuous epitopes, and drug molecules. Two methods of atomic hydrophilicity analysis provided a measure of complementarity in the interfaces of trypsin:pancreatic trypsin inhibitor and HIV protease:U-75875 inhibitor complexes. © 1995 Wiley-Liss, Inc.     

Circular dichroism of ketoprofen complexed to serum albumins: Conformational selection by the protein: A novel optical purity determination technique

Complexation of 2-(3′-benzoylphenyl)propionic acid (ketoprofen), 1 , to bovine serum albumin (BSA) results in an intense negative circular dichroism in the ketonic n → π* band of the benzoylphenyl moiety. This high CD contrasts with the weak CD of 1 -enantiomers dissolved in common solvents. Furthermore, a number of chiral and achiral molecules containing the benzophenone moiety are easily complexed to BSA: all these complexes show an intense CD at the same transition. To account for the observed CD intensities of the above molecules, it appears that BSA complexation markedly shifts the equilibrium between strongly asymmetric, antipodic conformers. Dissymmetry of these conformers is connected to the instability of a structure with phenyl rings coplanar to the carbonyl chromophore, as also indicated by molecular mechanics calculations. The magnification of the Cotton effects of the 1 -antipodes, due to the protein, can be used to measure the optical purity of 1 -samples with excellent precision. In contrast with BSA, human SA is unable to recognize the chirality of 1 -antipodes; oleic acid cocomplexation modifies this fact as well as other features of the binding. © 1995 Wiley-Liss, Inc.     

Developmental asynchrony caused by steep temperature gradients does not impair pattern formation in the wasp,Pimpla turionellae L.

Generating developmental gradients by temperature gradients established within a developing organism is an easy, non-invasive technique to study physiological interdependencies between locally separated subsystems. A linear temperature gradient of about 10° C/mm was maintained up to 5 h in either direction along the long axis of a long-germ-type hymenopteran egg, which was simultaneously filmed by the 16 mm timelapse technique. The result was a dramatic desynchronization of development, which between the egg poles could reach up to 9.3 h relative to normal development. Within the same egg, up to seven mitotic waves (i.e. eight different nuclear generations) were observed at the same time, and the subsequent cellularization process was extremely asynchronous. The initial regions of the mitotic waves, the fountain flow of the ooplasm, and the gastrulation process were shifted towards the egg pole kept at higher temperatures. Developmental processes occurring successively in normal development now took place simultaneously, with either direction of the temperature gradient. For instance, while gastrulation had started in the warm region, midblastula transition and cellularization were in progress in the middle of the egg, and intravitelline nuclear multiplication occurred at the cold pole, by rapid and still biphasic cell cycles. In some respects, development resembled that of a short-germ-type insect egg. Nevertheless, the developmental processes were resynchronized after the temperature gradient was switched off. Surprisingly, the extreme desynchronization during early development did not affect the segment pattern of the resulting embryos. The technique of inducing well-defined developmental asynchronies might be applied in Drosophila to analyse the subtle interplay between maternal and zygotic gene activities described in this species.     

Refined solution structure of human profilin I.

Profilin is a ubiquitous eukaryotic protein that binds to both cytosolic actin and the phospholipid phosphatidylinositol-4,5-bisphosphate. These dual competitive binding capabilities of profilin suggest that profilin serves as a link between the phosphatidyl inositol cycle and actin polymerization, and thus profilin may be an essential component in the signaling pathway leading to cytoskeletal rearrangement. The refined three-dimensional solution structure of human profilin I has been determined using multidimensional heteronuclear NMR spectroscopy. Twenty structures were selected to represent the solution conformational ensemble. This ensemble of structures has root-mean-square distance deviations from the mean structure of 0.58 A for the backbone atoms and 0.98 A for all non-hydrogen atoms. Comparison of the solution structure of human profilin to the crystal structure of bovine profilin reveals that, although profilin adopts essentially identical conformations in both states, the solution structure is more compact than the crystal structure. Interestingly, the regions that show the most structural diversity are located at or near the actin-binding site of profilin. We suggest that structural differences are reflective of dynamical properties of profilin that facilitate favorable interactions with actin. The global folding pattern of human profilin also closely resembles that of Acanthamoeba profilin I, reflective of the 22% sequence identity and approximately 45% sequence similarity between these two proteins.     

Structural basis of substrate specificity in the serine proteases.

Structure-based mutational analysis of serine protease specificity has produced a large database of information useful in addressing biological function and in establishing a basis for targeted design efforts. Critical issues examined include the function of water molecules in providing strength and specificity of binding, the extent to which binding subsites are interdependent, and the roles of polypeptide chain flexibility and distal structural elements in contributing to specificity profiles. The studies also provide a foundation for exploring why specificity modification can be either straightforward or complex, depending on the particular system.     

蚕茧近红外反射（NIR）光谱的模式识别──Ⅰ．对雌雄鲜茧、死笼茧的非破坏性识别

探讨了利用蚕茧近红外反向光谱识别雌雄茧、死笼茧的方法及可行性。采用６２５０型近红外光谱分析仪,从波长６８０ｎｍ到１２３５ｎｍ对２０５颗鲜茧做了非破坏性扫描测试,用逐步判别方法从一、二阶导数光谱数据中抽取特征向量,以此特征向量建立Ｂａｙｅｓ差别函数,对３７５个检验样本进行识别,其符合率达９５．７％,该方法明显优于以茧的重和大小差别雌雄的方法。实验结果还表明,雌雄茧近红外反射光谱的差别,主要是由于蚕肾     

蚕茧近红外反射（NIR）光谱的模式识别──Ⅰ．对雌雄鲜茧、死笼茧的非破坏性识别

探讨了利用蚕茧近红外反射光谱识别雌雄茧、死笼茧的方法及可行性。采用６２５０型近红外光谱分析仪,从波长６８０ｎｍ到１２３５ｎｍ对２０５颗鲜茧做了非破坏性扫描测试,用逐步判别方法从一、二阶导数光谱数据中抽取特征向量,以此特征向量建立Ｂａｙｅｓ判别函数,对３７５个检验样本进行识别,其符合率达９５．７％,该方法明显优于以茧的重量和大小判别雌雄的方法。实验结果还表明,雌雄茧近红外反射光谱的差别,主要是由于蚕蛹性质不同所致,而与茧层的关系不大。     

Differentiation of vegetation zones and species strategies in the subalpine region of Mt. Fuji

The floristic and structural differentiation of vegetation along the altitudinal gradient in four subalpine forests of different developmental stages on Mt. Fuji has been studied. Near the forest limit a micropattern of vegetation corresponding to the altitudinal zonation has been observed which elucidated the mechanisms of development of the vegetation zonation. As to early stages of vegetation development only two types can be distinguished: the volcanic desert above 1500 m and the pioneer forests below. As to later stages a differentiation of subzones includes from higher to lower altitudes: the Alnus maximowiczii, Betula ermanii, Abies veitchii and Tsuga diversifolia forests. Larix leptolepis and Sorbus americana ssp. japonica, appear as co-dominants in ecotonal communities between the principal subzones and are also important pioneers in early stages. Similarity analyses reveal that the upper subalpine Alnus-Betula forests can be regarded as early successional phases of the climax Abies-Tsuga forests of the lower subalpine zone. The regular arrangement of A. maximowiczii-B. ermanii-A. veitchii is studied along the gradient from the margin to the interior of the forest growing near the forest limit where locally favourable conditions prevail. Growth form, height growth, photosynthetic activity, seed supply, and seedling distribution of the three principal species have been compared, as well as biomass and production relations in contiguous forests of these species. The marginal Alnus type community is productive and disturbance-tolerant, and has a wide ecological and sociological amplitude along the gradient, while the central Abies community is accumulative and disturbance-intolerant, and has a narrower tolerance range, but is superior in competition under stable habitat conditions. A vegetation organization, ‘temporal multi-storeyed structure’, is suggested which means that a zonal pattern of vegetation within a climax region develops by successive replacement of successional species along an environmental gradient.