Crystallization of purple membrane in three dimensions

Large aggregates of purple membrane have been produced by solubilization of purple membrane in Triton X100, followed by removal of the detergent by dialysis against 0.9 m or 1.0 m-phosphate (pH 5.0). Although the crystals are not yet large enough for X-ray analysis, they appear microscopically crystalline in three dimensions, with space group P321 or P312.Freeze-fracture electron microscopy and diffraction analysis show that each membrane forming the aggregate has the normal P3 packing ($\text{a = 63}\text{A}\text{?}$). Membranes are arranged in pairs, with their extracellular surfaces in close contact, and these pairs then stack up to form large aggregates. The large aggregates appear to be perfect three-dimensional crystals only over small regions, up to 12 membranes thick. There are occasional inclusions of solvent between membrane pairs, and “coincidence lattice” defects occur.     

The alignment of protein structures in three dimensions

This article extends the use of dynamic programming algorithms in molecular sequence comparison to the alignment of the α-carbon (C_α-) coordinates of two protein structures in three dimensions. The algorithm is described in detail and is applied to the comparison of α-lactalbumin with both hen egg white lysozyme and T4 lysozyme. In the first case, the structures are similar, while the second comparison is between two distantly related molecules. References are made to the usual sequence alignments. A variety of complementary methods are introduced to display the results. National Research Council of Canada Publication No. 29461.     

Fluctuation-driven flocking movement in three dimensions and scale-free correlation

Recent advances in the study of flocking behavior have permitted more sophisticated analyses than previously possible. The concepts of "topological distances" and "scale-free correlations" are important developments that have contributed to this improvement. These concepts require us to reconsider the notion of a neighborhood when applied to theoretical models. Previous work has assumed that individuals interact with neighbors within a certain radius (called the "metric distance"). However, other work has shown that, assuming topological interactions, starlings interact on average with the six or seven nearest neighbors within a flock. Accounting for this observation, we previously proposed a metric-topological interaction model in two dimensions. The goal of our model was to unite these two interaction components, the metric distance and the topological distance, into one rule. In our previous study, we demonstrated that the metric-topological interaction model could explain a real bird flocking phenomenon called scale-free correlation, which was first reported by Cavagna et al. In this study, we extended our model to three dimensions while also accounting for variations in speed. This three-dimensional metric-topological interaction model displayed scale-free correlation for velocity and orientation. Finally, we introduced an additional new feature of the model, namely, that a flock can store and release its fluctuations.     

Mo-MuLV nucleotide sequence exhibits three levels of oligomeric repetitions,suggesting a stepwise molecular evolution

Summary An exhaustive computer-assisted analysis of the Moloney murine leukemia virus nucleotide sequence shows numerous deviations in the oligomeric distribution, suggesting three overlapping levels of a stepwise duplicative evolution. (1) The sequence fits the universal rule of TG/CT excess which has been proposed as the construction principle of all sequences, and maintains some degree of symmetry between the two complementary strands. (2) Oligomeric repeating units share a core consensus regularly scattered throughout the sequence. This consensus is not merely predictable from the doublet frequencies and codon usage, but could correspond to an intermediary stage in a so-called periodic-to-chaotic transition. (3) Probable stepwise local duplications could be accounted for by slippagelike mechanisms. Comparison with the human spumaretrovirus (HSRV) shows similar segments in the overrepresented oligomers of the two sequences. The intermediary stage of transition oligomeric repeating units is not so clearly suggested in HSRV, perhaps because of numerous stepwise local duplications. In any case, a common evolutionary origin for the two viruses is not ruled out.     

Time and length scales of autocrine signals in three dimensions

A model of autocrine signaling in cultures of suspended cells is developed on the basis of the effective medium approximation. The fraction of autocrine ligands, the mean and distribution of distances traveled by paracrine ligands before binding, as well as the mean and distribution of the ligand lifetime are derived. Interferon signaling by dendritic immune cells is considered as an illustration.     

Magnitude and variations of groundwater seepage along a Florida marine shoreline

Direct groundwater inputs are receiving increasingattention as a potential source of nutrients and otherdissolved constituents to the coastal ocean. Seepageinto St. George Sound, Florida was measuredextensively from 1992 to 1994 using seepage meters. Spatial and temporal variations were documented alonga 7-km stretch of coastline and up to 1 km from shore. Measurements were made at 3 transects perpendicular toshore and 1 transect parallel to shore. The generalresults indicated that seepage decreased with distancefrom shore (2 of 3 transects), and substantialtemporal and spatial variability was observed inseepage flow from nearshore sediments. In addition,trends in mean monthly integrated seepage rates weresimilar to precipitation patterns measured at a nearbycoastal weather station. Based on these measurements, weestimate that the magnitude of groundwater seepage intothe study area is substantial, representing from 0.23 to4.4 m3 sec-1of flow through the sediments, approximately equivalentto a first magnitude spring. Although it is unknown howrepresentative this region is with respect to globalgroundwater discharge, it demonstrates thatgroundwater flow can be as important as riverine andspring discharge in some cases. Our subsurfacedischarge rates suggest groundwater is an importanthydrologic source term for this region and may beimportant to the coastal biogeochemistry as well.     

Sun protection and Vitamin D: three dimensions of obfuscation

Ultraviolet (UV) radiation is a proven carcinogen, responsible for more than half of all human malignancies. It also compromises skin appearance and function. Since the UV action spectra for DNA damage, skin cancer and Vitamin D₃ (vit D) photosynthesis are identical and vit D is readily available from oral supplements, why has sun protection become controversial, now that some data suggest conventionally “sufficient” levels of vit D may be less than optimal for at least some population groups? First, the media and apparently some researchers are hungry for a new message. Nevertheless, after 50 years, UV exposure is still a major avoidable health hazard. Second, the controversy is fueled by a powerful special interest group: the indoor tanning industry. They target not the frail elderly or inner-city ethnic minorities, groups for whom evidence of vit D insufficiency is strongest, but rather fair-skinned teenagers and young adults, those at highest risk of UV photodamage. Third, evolution does not keep pace with civilization. When nature gave man the appealing capacity for vit D photosynthesis, the expected lifespan was far less than 40 years. Long-term photodamage was not a concern, and vit D was not available at the corner store. The medical community should avoid sensationalism and instead rigorously explore possible cause-and-effect relationships between vit D status and specific diseases while advocating the safest possible means of assuring vit D sufficiency.     

In-silico patterning of vascular mesenchymal cells in three dimensions

Cells organize in complex three-dimensional patterns by interacting with proteins along with the surrounding extracellular matrix. This organization provides the mechanical and chemical cues that ultimately influence a cell's differentiation and function. Here, we computationally investigate the pattern formation process of vascular mesenchymal cells arising from their interaction with Bone Morphogenic Protein-2 (BMP-2) and its inhibitor, Matrix Gla Protein (MGP). Using a first-principles approach, we derive a reaction-diffusion model based on the biochemical interactions of BMP-2, MGP and cells. Simulations of the model exhibit a wide variety of three-dimensional patterns not observed in a two-dimensional analysis. We demonstrate the emergence of three types of patterns: spheres, tubes, and sheets, and show that the patterns can be tuned by modifying parameters in the model such as the degradation rates of proteins and chemotactic coefficient of cells. Our model may be useful for improved engineering of three-dimensional tissue structures as well as for understanding three dimensional microenvironments in developmental processes.     

Epigenetics and twins: three variations on the theme

Twin studies have had a key role in the evaluation of heritability, a population-based estimate of the genetic contribution to phenotypic variation. These studies have led to the revelation that most normal and disease phenotypes are to some extent heritable. Recently, interest has shifted from phenomenological heritability to the identification of trait-specific genes. The era of twin studies, however, is not over: recent epigenetic and global gene expression studies suggest that the most interesting findings in twin-based research are still to come. The increasing realization of the influence of epigenetics in phenotypic outcomes means that the molecular mechanisms behind phenotypic differences in genetically identical organisms can be explored. Analyses of epigenetic twin differences and similarities might yet challenge the fundamental principles of complex biology, primarily the dogma that complex phenotypes result from DNA sequence variants interacting with the environment.     

Theory of electric signals of membrane proteins in three dimensions

Transmembrane ion pumps are often investigated experimentally by photoelectric measurements in model systems. In addition to the most widely used systems based on model membranes, a fundamentally different class is represented by the so-called suspension methods. In this technique the electric signal is measured on a bulk suspension of oriented ion pumps in the form of a displacement current. On this system, electric and spectroscopic experiments can be performed simultaneously. Using the information from both types of measurements, and utilizing the three-dimensional nature of the system, it is possible to follow the intramolecular charge motions in all three spatial directions. The derivable dipole moment changes associated with conformational transitions allow the verification of molecular dynamic models. In this work a theory is presented to describe the suspension method; samples with different symmetry properties and the possibilities of photoselection to obtain the desired three-dimensional information are analyzed.     

Effects of viral mutation on cellular dynamics in a monte carlo simulation of HIV immune response model in three dimensions

Summary The cellular dynamics of HIV interaction with the immune system is explored in three-dimensions using a direct Monte Carlo simulation. Viral mutation with probability, Pmut, is considered with immobile and mobile cells. With immobile cells, the viral population becomes larger than that of the helper cells beyond a latency period Tcrit and above a mutation threshold Pcrit. That is at Pmut ≥ Pcrit, { }, with γ ⋍ 0.73 in three dimensions and γ ⋍ 0.88 in 2-D. Very little difference in Pcrit is observed between two and three dimensions. With mobile cells, no power-law is observed for the period of latency, but the difference in Pcrit between two and three dimensions is increased. The time-dependency of the density difference between Viral and Helper cell populations (ρV − ρH) is explored and follows the basic pattern of an immune response to infection. This is markedly more defined than in the 2-D case, where no clear pattern emerges.     

Control of cell migration in two and three dimensions using substrate morphology

We have shown that en masse cell migration of fibroblasts on the planar surface results in a radial outward trajectory, and a spatially dependent velocity distribution that decreases exponentially in time towards the single cell value. If the cells are plated on the surface of aligned electropsun fibers above 1 μm in diameter, they become polarized along the fiber, expressing integrin receptors which follow closely the contours of the fibers. The velocity of the cells on the fibrous scaffold is lower than that on the planar surface, and does not depend on the degree of orientation. Cells on fiber smaller than 1 μm migrate more slowly than on the planar surface, since they appear to have a large concentration of receptors. True three-dimensional migration can be observed when plating the droplet on a scaffold comprises of at least three layers. The cells still continue to migrate on the fibers surfaces, as they diffuse into the lower layers of the fibrous scaffold.