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Capsid protein determinants involved in cell-to-cell and long distance movement of tobacco etch potyvirus.

The tobacco etch potyvirus (TEV) capsid protein (CP) is necessary for cell-to-cell and long distance transport of the virus in plants. In this study, the transport phenotypes of TEV mutants containing CPs with a substitution of the highly conserved Ser122 (termed S122W) within the core domain, or with a deletion of sequences encoding 17 amino acid residues comprising most of the variable C-terminal domain (delta C), were analyzed. The S122W and delta C mutant genomes were amplified to levels comparable to parental virus in protoplasts. The S122W mutant was encapsidation-defective, although in transgenic plants expressing wild-type CP a small number of virions were observed after prolonged incubation. Cells infected by the delta C mutant produced virions, indicating that the C-terminal domain is not necessary for encapsidation. The mutants exhibited unique defects in cell-to-cell and long distance movement in plants. The S122W mutant was confined to single, primarily inoculated epidermal cells in nontransgenic plants, but the cell-to-cell movement defect was rescued efficiently by transgenic CP. Long distance movement of this mutant was also rescued in transgenic plants, but accumulation in systemically infected tissue was low compared to parental virus. The delta C mutant exhibited a slow cell-to-cell movement phenotype in inoculated leaves and a complete inability to move systemically in nontransgenic plants. Transgenic CP was able to rescue partially the slow cell-to-cell movement defect of the delta C mutant, but not the long distance transport defect. Taken together with previous results, these data suggest that the core domain of TEV CP provides a function essential during cell-to-cell movement and that the variable N- and C-terminal regions exposed on the virion surface are necessary for long distance transport. In addition, trans-inhibition models are presented to account for the widely differing transgenic complementation efficiencies of the various movement-defective mutants.

Capsid↗

A protein alignment scoring system sensitive at all evolutionary distances.

Protein sequence alignments generally are constructed with the aid of a "substitution matrix" that specifies a score for aligning each pair of amino acids. Assuming a simple random protein model, it can be shown that any such matrix, when used for evaluating variable-length local alignments, is implicitly a "log-odds" matrix, with a specific probability distribution for amino acid pairs to which it is uniquely tailored. Given a model of protein evolution from which such distributions may be derived, a substitution matrix adapted to detecting relationships at any chosen evolutionary distance can be constructed. Because in a database search it generally is not known a priori what evolutionary distances will characterize the similarities found, it is necessary to employ an appropriate range of matrices in order not to overlook potential homologies. This paper formalizes this concept by defining a scoring system that is sensitive at all detectable evolutionary distances. The statistical behavior of this scoring system is analyzed, and it is shown that for a typical protein database search, estimating the originally unknown evolutionary distance appropriate to each alignment costs slightly over two bits of information, or somewhat less than a factor of five in statistical significance. A much greater cost may be incurred, however, if only a single substitution matrix, corresponding to the wrong evolutionary distance, is employed.

Algorithms↗

Intrinsic nature of the three-dimensional structure of proteins as determined by distance geometry with good sampling properties.

A protocol for distance geometry calculation is shown to have excellent sampling properties in the determination of three-dimensional structures of proteins from nuclear magnetic resonance (NMR) data. This protocol uses a simulated annealing optimization employing mass-weighted molecular dynamics in four-dimensional space (Havel, T.F. (1991) Prog. Biophys. Mol. Biol., 56, 43-78). It attains an extremely large radius of convergence, allowing a random coil conformation to be used as the initial estimate for the succeeding optimization process. Computations are performed with four systems of simulated distance data as tests of the protocol, using an unconstrained L-alanine 30mer and three different types of proteins, bovine pancreatic trypsin inhibitor, the alpha-amylase inhibitor Tendamistat, and the N-terminal domain of the 434-repressor. The test of the unconstrained polypeptide confirms that the sampled conformational space is that of the statistical random coil. In the larger and more complicated systems of the three proteins, the protocol gives complete convergence of the optimization without any trace of initial structure dependence. As a result of an exhaustive conformational sampling by the protocol, the intrinsic nature of the structures generated with distance restraints derived from NMR data has been revealed. When the sampled structures are compared with the corresponding X-ray structures, we find that the averages of the sampled structures always show a certain pattern of discrepancy from the X-ray structure. This discrepancy is due to the short distance nature of the distance restraints, and correlates with the characteristic shape of the protein molecule.

Animals↗

Estimation of inter-binding-site distances in sarcoplasmic reticulum (Ca2+ + Mg2+)-ATPase under occluded and non-occluded conditions.

Distances between binding sites in skeletal sarcoplasmic reticulum (Ca2+ + Mg2+)-ATPase were estimated by measuring energy transfer between a luminescent lanthanide probe for the calcium sites (Eu3+) and suitable acceptors. A distance measurement between the two calcium binding sites of the enzyme was made with and without MgATP, corresponding to two different states in the hydrolytic cycle. We found that without ATP, the inter-calcium-site distance is about 0.9 nm, while in the presence of MgATP these sites are 0.05 nm to 0.1 nm closer. We also estimated the distance from the calcium sites to the hydrolytic site using CrATP as an acceptor; this distance is approximately 1.8 nm. These measurements provide the start for a description of intramolecular movement during the transport cycle, and should be of use in mapping out the three-dimensional structure of the Ca2+ pump.

Animals↗

Is there a general relationship between estimated chromosome distances in interphase and location of genes with related functions?

The problem of a possible clustering of human chromosomes containing genes with related functions was examined in the interphase nucleus of lymphocytes by a statistical comparison of distances between chromosomes containing such functionally related genes with all sets of chromosome distances. The gene locus assignments were taken from a recent review (McKusick 1982); the chromosomal distances were those estimated by Hager et al. (1982) from the frequencies of reunion figures between specific chromosomes as observed in chromosome instability syndromes (Fanconi anemia, Bloom syndrome) and after treatment with Trenimon. Chromosomal distances had been estimated by multidimensional scaling. There was no general tendency for closer location of chromosomes containing genes with related function. A few such chromosomes do show below average distances but this could easily be a chance result.

Cell Nucleus↗

Performance evaluation of OSEM reconstruction algorithm incorporating three-dimensional distance-dependent resolution compensation for brain SPECT: a simulation study.

UNLABELLED: Iterative reconstruction techniques such as an ordered subsets-expectation maximization (OSEM) algorithm can easily incorporated various physical models of attenuation or scatter. We implemented OSEM reconstruction algorithm incorporating compensation for distance-dependent blurring due to the collimator in SPECT. The algorithm was examined by computer simulation to estimate the accuracy for brain perfusion study. METHODS: The detector response was assumed to be a two-dimensional Gauss function and the width of the function varied linearly with the source-to-detector distance. The attenuation compensation (AC) was also included. To investigate the properties of the algorithm, we performed computer simulations with the point source and digital brain phantoms. In the point source phantom, the uniformity of FWHM for the radial, tangential and longitudinal directions was evaluated on the reconstruction image. As for the brain phantom, quantitative accuracy was estimated by comparing the reconstructed images with the true image by the mean square error (MSE) and the ratio of gray and white matter counts (G/W). Both noise free and noisy simulations were examined. RESULTS: In the point source simulation, FWHM in radial, tangential and longitudinal directions were 14.7, 14.7 and 15.0 mm at the image center and were 15.9, 9.83 and 10.6 mm at a distance of 15 cm from the center by using FBP, respectively. On the other hand, they were 8.12, 8.12 and 7.83 mm at the image center, and were 7.45, 7.44 and 7.01 mm at 15 cm from the center by OSEM with distance-dependent resolution compensation (DRC). An isotropic and stationary resolution was obtained at any location by OSEM with DRC. The spatial resolution was also improved about 6.5 mm by OSEM with DRC at the image center. In the brain phantom simulation, the blurring at the edge of the brain structure was eliminated by using OSEM with both DRC and AC. The G/W was 2.95 and 2.68 for noise free and noisy cases, respectively, when no compensation was performed. But the values for G/W without and with noise became 3.45 and 3.21 with AC only and were improved to 3.75 and 3.71 with both AC and DRC. The G/W approached the true value (4.00) by using OSEM with both AC and DRC even when there was statistical noise. CONCLUSION: In conclusion, OSEM reconstruction including the distance-dependent resolution compensation algorithm was reasonably successful in achieving isotropic and stationary resolution and improving the quantitative accuracy for brain perfusion SPECT.

Algorithms↗

The distance from the skin to the subarachnoid space can be predicted in premature and former-premature infants.

PURPOSE: Spinal anesthesia can be technically challenging in young infants. We studied whether the distance between the skin and the lumbar subarachnoid space in premature and former-premature young infants could be predicted prior to lumbar puncture. METHODS: The distance from skin entry point to tip of the spinal needle was measured using a caliper after lumbar spinal anesthesia at the L4-5 interspace. This distance was correlated to the patient's weight, postconceptual age and lumbar ultrasonographic measurement of the skin-to-subarachnoid space and predictive statistical models were sought. RESULTS: Thirty-five premature or former-premature infants were studied. Three models were examined: all three independent variables, weight and postconceptual age only, and weight only. The model selected contained the weight and postconceptual age, because it had the highest value for adjusted R squared, as well as the lowest value for the mean squared error. Adding the ultrasonic measurement to the model worsened the results. The statistical model that described the depth of the subarachnoid space at the L4-5 level was Y = 13.19 + 0.0026 x W - 0.12 x PCA, where Y is the distance (mm) from the skin to the subarachnoid space, W is the patient's weight (g) and PCA is the postconceptual age (weeks). Adjusted R squared was 0.72, mean square error was 2.63 and P < 10(-9). CONCLUSION: The distance between the skin and the subarachnoid space at the level of L4-5 interspace can be predicted using a statistical model based on the infant's weight and postconceptual age. Spinal ultrasound has no value in L4-5 subarachnoid space depth prediction.

Anesthesia, Spinal↗

Investigations on the palatal rugae pattern in cleft patients. Part II: Changes in the distances from the palatal rugae to maxillary points.

The study investigated the relationship of the palatal rugae to points and distances of the cleft palate during the time period from birth to early mixed dentition in subjects with unilateral and bilateral cleft lip and palate by means of a three-dimensional measuring system. The changes identified in the distances from the lateral palatal rugae points of the first and third rugae to the incisal point, the canine point and the tuberosity line made it possible to assess how growth and the various forms of therapy applied affected the position of the palatal rugae during the study period (from birth to early mixed dentition). Changes in the linear distances from the palatal rugae to the maxillary measuring points were identified during preoperative therapy, after lip surgery, and after palate surgery. A comparison of the distances from the palatal rugae with distances between equivalent points (incisal point-canine point, canine point-tuberosity line, canine point-canine point) revealed differences in some instances. The results suggest that the palatal rugae in combination with measuring points of the cleft palate can serve to depict the changes occurring in the anterior palate during various stages of therapy and growth.

Cephalometry↗

Permutation tests for the correlation among genetic distances and measures of heterosis.

It is often found that heterosis tends to increase with genetic distance of the parents, though the correlation is not usually very close. It is therefore important to test the null hypothesis that the correlation is zero. The present work shows that standard procedures tend to yield too liberal tests, owing to the lack of independence among genetic distances and among heterosis estimates. A valid alternative is to use a permutation test, which was first suggested by Mantel [(1967) Cancer Res 27: 209--220). This test is well-known among plant breeders and geneticists, who often use it to test the correlation among two distance matrices. Its use is not restricted to the comparison of distance matrices. This is demonstrated in the present work, using two published datasets on marker-based genetic distances of maize inbreds or populations and heterosis of their crosses. It is shown that the test is also applicable in the presence of missing data.

Breeding↗

Monocular and binocular distance cues: insights from visual form agnosia I (of III).

The human nervous system constructs a Euclidean representation of near (personal) space by combining multiple sources of information (cues). We investigated the cues used for the representation of personal space in a patient with visual form agnosia (DF). Our results indicated that DF relies predominantly on binocular vergence information when determining the distance of a target despite the presence of other (retinal) cues. Notably, DF was able to construct an Euclidean representation of personal space from vergence alone. This finding supports previous assertions that vergence provides the nervous system with veridical information for the construction of personal space. The results from the current study, together with those of others, suggest that: (i) the ventral stream is responsible for extracting depth and distance information from "monocular" retinal cues (i.e. from shading, texture, perspective) and (ii) the dorsal stream has access to binocular information (from horizontal image disparities and vergence). These results also indicate that DF was not able to use size information to gauge target distance, suggesting that intact temporal cortex is necessary for "learned size" to influence distance processing. Our findings further suggest that in neurologically intact humans, object information extracted in the ventral pathway is combined with the products of dorsal stream processing for guiding prehension. Finally, we studied the "size-distance paradox" in visual form agnosia in order to explore the cognitive use of size information. The results of this experiment were consistent with a previous suggestion that the paradox is a cognitive phenomenon.

Agnosia↗

A distance effect in a manual aiming task to remembered targets: a test of three hypotheses.

It has been noted that manual aiming error and variability when pointing to remembered targets increase as a function of target eccentricity. In the present study we evaluated which one of three hypotheses (target localization, motor, or movement duration) best explains this 'distance effect'. In experiment 1, older and younger participants aimed with their unseen hand at the remembered location of targets distributed between 129 and 309 mm from the starting base. Target presentation time was of either 50 or 500 ms and aiming movements could be initiated following either a 100- or a 10,000-ms recall delay. Participants had either no constraints concerning movement time or were asked to reach the near target in a longer movement time than the farther targets. The results revealed a significant distance effect when no time constraints were imposed but showed a significantly reversed distance effect when the instructions were to reach the near targets in a longer movement time than the far targets. The same results were obtained regardless of target presentation time, recall delay, or age of the participants. These results supported a movement duration interpretation of the distance effect. In experiment 2, a distance effect was replicated when pointing with one's unseen hand toward a remembered target but did not take place when pointing to visible targets. Taken together these results suggest that prolonged movement execution interferes with the stored egocentric target representation.

Adult↗

Recent evolutionary history of human immunodeficiency virus type 1 subtype B: reconstruction of epidemic onset based on sequence distances to the common ancestor.

We obtained and studied HIV-1 sequences with a known sampling year from three outbreaks of the HIV-1 epidemic: 141 env V3 (270 nt) sampled between 1984 and 1992 and 117 pol prot/RT (804 nt) sequences sampled between 1986 and 1999 from Dutch homosexual men and injecting drug users (IDUs), as well as 77 env V3 sequences sampled between 1983 and 1994 in the United States. Since retrospective serological and/or epidemiological data on these populations are available, providing estimates of the dates of the onset of the HIV-1 epidemics, we had the opportunity to test different phylogenetic models for their accuracy in deriving the recent evolutionary history of HIV-1 subtype B and the onset date of the HIV-1 epidemic. We observed that, in any given year, individual sequences vary widely in their distances to the common ancestor, and sequences close to the ancestors were found decades after the onset of the epidemic. Nevertheless, the mean evolutionary distances of virus strains to ancestors were increasing significantly during the course of the studied epidemics, which indicates that the molecular clock is operational in the recent evolution of HIV-1. When the relationship between the sampling years of sequences and their nucleotide distances to the common ancestor was extrapolated to the past, analysis of pol sequences provided accurate estimates of the onset years of the epidemics, whereas analysis of V3 sequences by the maximum-likelihood or neighbor-joining methods led to an overestimation of the age of the epidemics. Separate analysis of nonsynonymous and synonymous distances revealed that this overestimation results from nonsynonymous substitutions, whose numbers were not increasing significantly in all three virus populations over the observation period. In contrast, analysis of synonymous env V3 distances provided accurate estimates of the onset years for the outbreaks we studied.

Biological Evolution↗

Distance-based genome rearrangement phylogeny.

Evolution operates on whole genomes through direct rearrangements of genes, such as inversions, transpositions, and inverted transpositions, as well as through operations, such as duplications, losses, and transfers, that also affect the gene content of the genomes. Because these events are rare relative to nucleotide substitutions, gene order data offer the possibility of resolving ancient branches in the tree of life; the combination of gene order data with sequence data also has the potential to provide more robust phylogenetic reconstructions, since each can elucidate evolution at different time scales. Distance corrections greatly improve the accuracy of phylogeny reconstructions from DNA sequences, enabling distance-based methods to approach the accuracy of the more elaborate methods based on parsimony or likelihood at a fraction of the computational cost. This paper focuses on developing distance correction methods for phylogeny reconstruction from whole genomes. The main question we investigate is how to estimate evolutionary histories from whole genomes with equal gene content, and we present a technique, the empirically derived estimator (EDE), that we have developed for this purpose. We study the use of EDE on whole genomes with identical gene content, and we explore the accuracy of phylogenies inferred using EDE with the neighbor joining and minimum evolution methods under a wide range of model conditions. Our study shows that tree reconstruction under these two methods is much more accurate when based on EDE distances than when based on other distances previously suggested for whole genomes.

Algorithms↗

The interior-to-edge breakpoint distance as a guideline for nature conservation policy.

A method is proposed to quantify disturbance impact on isolated habitats. For every landscape patch, the breakpoint distance, defined as the penetration distance for which equality of interior and edge habitat is observed, can be calculated. Disturbance with equal impact at all patch sides is assumed. Effects of patch compactness, size, convolution, and perforation are discussed. The potential use of the measure for nature reserve design is discussed. The breakpoint distance follows the reserve design guidelines for individual patches, based on island biogeography and is consistent with the form and function principle. A large breakpoint distance is preferred for natural habitats. Small size, small compactness, intense convolution, and the occurrence of many gaps depress the breakpoint distance.

Animals↗

The Hiroshima thermal-neutron discrepancy for (36)Cl at large distances. Part II: Natural in situ production as a source.

For Hiroshima, a large discrepancy between calculated and measured thermal-neutron fluences had been reported in the past, for distances to the epicenter larger than about 1,000 m. To be more specific, measured (36)Cl concentrations in environmental samples from Hiroshima were too large at these distances, and the ratio of measured to calculated values reached about 70, at a distance of 1,800 m. In an attempt to identify other sources that might also produce (36)Cl in Hiroshima samples, the role of cosmic rays and of neutrons from natural terrestrial sources was investigated. Four reaction mechanisms were taken into account: spallation reactions of the nucleonic (hadronic) component of the cosmic rays on potassium (K) and calcium (Ca) in the sample material, particle emission after nuclear capture of negative muons by K and Ca, reactions of fast-muon induced electromagnetic, and hadronic showers with K and Ca, and neutron capture reactions with (35)Cl in the sample where the neutrons originate from the above three reaction mechanisms and from uranium and thorium decay. These mechanisms are physically described and mathematically quantified. It is shown that among those parameters important for the production of (36)Cl in granite, the chemical composition of the sample, the depth in the quarry where the sample had initially been taken, and the erosion rate at the site of the quarry are most important. Based on these physical, chemical, and geological parameters, (36)Cl concentrations were calculated for different types of granite that are typical for the Hiroshima area. In samples that were of these granite types and that had not been exposed to atomic bomb(A-bomb) neutrons, the (36)Cl concentration was also determined experimentally by means of accelerator mass spectrometry, and good agreement was found with the calculated values. The (36)Cl signal due to natural in situ production was also calculated in granite samples that had been exposed to A-bomb neutrons at distances up to 1,500 m from the hypocenter. It is demonstrated that, for granite samples from Hiroshima exposed to A-bomb neutrons beyond distances of about 1,300 m from the hypocenter, the (36)Cl signal is dominated by natural in situ production.

Biophysical Phenomena↗

Factors limiting cold-water swimming distance while wearing personal floatation devices.

The influence of body adiposity, arm skinfold thickness, aerobic capacity, and cooling rate were studied in a mock survival swimming situation conducted in water at around 14 degrees C. Seventeen adult participants wore personal floatation devices on top of seasonal clothing and were asked to swim as far as they could, as if attempting to reach shore following an accidental immersion in cold water. Triceps and patellar skinfold thickness showed a significant correlation with distance covered (r = 0.70 and 0.56, respectively), while abdominal skinfold and percent body fat showed no significant correlation. Maximum oxygen consumption (VO2max) was not significantly related to distance covered. There was a negative correlation between body cooling rate during the swimming period and distance covered. A multiple stepwise regression analysis, however, indicated that the only significant contributor to variance in the distance covered was the triceps skinfold thickness (r2 = 0.49). It was concluded that for a healthy subject accidentally immersed in cold water, triceps skinfold thickness is a stronger predictor of the swimming distance covered than body adiposity, VO2max, or the drop in core temperature.

Abdomen↗

Localisation and distance between ABL and BCR genes in interphase nuclei of bone marrow cells of control donors and patients with chronic myeloid leukaemia.

Quantitative measurements of the nuclear localisation of the ABL and BCR genes and the distance between them were performed in randomly oriented bone marrow cells of control donors and patients with chronic myeloid leukaemia (CML). Most ABL and BCR genes (75%) are located at a distance of 20-65% of the local radius from the nuclear centre to the nuclear membrane. A chimeric BCR-ABL gene located on a derivative chromosome 22 resulting from t(9;22)(q34;q11) [the so-called Philadelphia (Ph) chromosome] as well as the intact ABL and BCR genes of patients suffering from chronic myeloid leukaemia are also located mostly in this region, which has a mean thickness of 2 microns in bone marrow cells. We have not found any significant differences in the location of the two genes in the G1 and G2 phases of the cell cycle, nor between bone marrow cells and stimulated lymphocytes. Irradiation of lymphocytes with a dose of 5 Gy of gamma-rays results in a shift of both genes to the central region of the nucleus (0-20% of the radius distant from the nuclear centre) in about 15% of the cells. The minimum distance between one ABL and one BCR gene is less than 1 micron in 47.5% of bone marrow cells of control donors. Such a small distance is found between homologous ABL and between homologous BCR genes in only 8.1% and 8.4% of cells, respectively. It is possible that the relative closeness of nonhomologous ABL and BCR genes in interphase nuclei of bone marrow cells could facilitate translocation between these genes. In 16.4% of bone marrow cells one ABL and one BCR gene are juxtaposed (the distance between them varies from 0-0.5 micron) and simulate the Ph chromosome. This juxtaposition is the result of the projection of two genes located one above another into a plane, as follows from the probability calculation.

Adult↗

Electrogastrographic power ratio in humans is not related to changes in antrum-skin distance but to antral motility.

It is not clear whether the power increase in electrogastrography (EGG) after meal or water ingestion reflects increases in gastric motility or gastric distension bringing the stomach closer to the electrodes on the abdominal skin surface. We recorded EGG and real-time ultrasonography simultaneously before and after 150-ml water ingestion in 17 healthy volunteers. We calculated gastric power, by spectral analysis of EGG by the maximum entropy method, for 400 s before and after water ingestion, and calculated their ratio (power ratio). We calculated, using sonography, the number of antral contractions before and after water ingestion, the motility index after water ingestion, the distance between the antrum and the abdominal skin surface before and after water ingestion, and the ratio of these distances (distance ratio). The number of contractions was positively correlated with gastric power before water ingestion, and the antrum-skin distance was negatively correlated with gastric power both before and after water ingestion. The motility index after water ingestion was positively correlated with both gastric power after water ingestion (Spearman's rank correlation r = 0.492; P = 0.0498) and the power ratio (r = 0.615; P = 0.0141). There was no correlation between the distance ratio and the power ratio. These results suggest that the power increase in EGG induced by water ingestion does not reflect the approach of the antrum to the abdominal surface, but rather, reflects antral motility after water ingestion.

Adult↗