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Epigenetic interactions and the structure of phenotypic variation in the cranium.

Understanding the developmental and genetic basis for evolutionarily significant morphological variation in complex phenotypes such as the mammalian skull is a challenge because of the sheer complexity of the factors involved. We hypothesize that even in this complex system, the expression of phenotypic variation is structured by the interaction of a few key developmental processes. To test this hypothesis, we created a highly variable sample of crania using four mouse mutants and their wild-type controls from similar genetic backgrounds with developmental perturbations to particular cranial regions. Using geometric morphometric methods we compared patterns of size, shape, and integration in the sample within and between the basicranium, neurocranium, and face. The results highlight regular and predictable patterns of covariation among regions of the skull that presumably reflect the epigenetic influences of the genetic perturbations in the sample. Covariation between relative widths of adjoining regions is the most dominant factor, but there are other significant axes of covariation such as the relationship between neurocranial size and basicranial flexion. Although there are other sources of variation related to developmental perturbations not analyzed in this study, the patterns of covariation created by the epigenetic interactions evident in this sample may underlie larger scale evolutionary patterns in mammalian craniofacial form.

Animals↗

A new mechanism of Raman enhancement and its application.

Strong electronic Raman bands corresponding to the transition between 4I9/2 and 4I11/2 manifolds of Nd3+, caused by a Raman-enhancement effect, are observed in the FT-Raman spectrum of Nd2O3. Neither resonance enhancement (RR) nor surface enhancement (SERS) accounts for the Raman enhancement observed here. We propose a new mechanism of Raman enhancement called the "feed-back" mechanism. A YAG laser excites the final state of the Raman transition (4I11/2 of Nd3+) to the 4F3/2 state and causes a significant decrease in the population of Nd3+ at the 4I11/2 state. This causes the population ratio of Nd3+ at 4I9/2 and 4I11/2 to deviate from the value required by Boltzmann's law. To restore equilibrium, Raman scattering is enhanced so that more Nd3+ ions are brought from the 4I9/2 state to the 4I11/2 state. This hypothesis gets support from the temperature-variable FT-Raman spectroscopic results. Additionally, obvious differences between the Stokes and anti-Stokes Raman spectrum of Nd3+ provide further evidence to support the feed-back mechanism. The Raman-enhancement effect confers on the electronic Raman bands a special ability to reflect the variation of coordinated structure around metal ions. The structural variations in polymer-metal ion composites and biomineralization systems have been investigated by using the electronic Raman bands.

Journal Article↗

Straight wire: the next generation.

Frequently, the anticipated results of treatment are not achieved by using preadjusted appliances and straight wires. This is due to inaccurate bracket placement, variations in tooth structure, variations in the maxillary/mandibular relationships, tissue rebound, and mechanical deficiencies of edgewise orthodontic appliances. Clearly, one preadjusted appliance prescription cannot fit all orthodontic patients. Individualized prescriptions for preadjusted orthodontic appliances can be fabricated once all of these reasons are recognized. From the cephalogram and visual treatment objective, the desired position of maxillary and mandibular incisors can be determined according to the maxillary/mandibular relationships. The torque angle of the labial surface of maxillary and mandibular incisors relative to the arch wire plane can be measured with an incisor torque template. The development and refinement of a system to vary the orientation of the bracket arch wire slot relative to the labial surface of each tooth provides a solution to these problems. Beyond the accuracy or inaccuracy of bracket placement and the fact that brackets are placed away from the center of resistance, orthodontic appliances have two additional significant mechanical deficiencies; play between the arch wire and the arch wire slot, and force diminution. These deficiencies cannot be eliminated from current appliances, however, they can be minimized by using reasonably stiff arch wires approximating the size of the arch wire slots. The amount of play plus the amount of force diminution inherent in your appliance can be added to or subtracted from the torque, tip, rotation, and height parameters for each bracket to deliver the teeth to the desired positions. Therefore treatment goals can be achieved with maximum efficiency.

Dental Bonding↗

Multiscale simulation of transmembrane proteins.

Multiscale simulation is employed to examine changes in atomistic-level protein structure due to long wavelength membrane undulations and plane stress fields. An ensemble of atomistic-level simulations of a model of a transmembrane influenza A virus M2 proton channel in a dimyristoylphosphatidylcholine (DMPC) bilayer is coupled to a corresponding mesoscopic model of a DMPC bilayer in an explicit mesoscopic solvent. Structural variations in the key proton gating His37 residues of the M2 channel are examined. Small, but distinct variations in the structure of the His37 residues are observed in both the open and closed states of the channel as a result of the coupling to mesoscopic-level membrane motions.

Dimyristoylphosphatidylcholine↗

Genetic variation and population structure in the endangered greater horseshoe bat Rhinolophus ferrumequinum.

Following a dramatic decline last century, the British population of the endangered greater horseshoe bat Rhinolophus ferrumequinum is highly fragmented. To examine the consequences of fragmentation and limited dispersal on patterns of genetic structure and variation, we used microsatellite markers to screen bats from around 50% of the known maternity colonies in Britain, and two areas from continental Europe. Analyses revealed that Welsh and English colonies were genetically isolated. This, and lower variability in Britain than north France, may result from either genetic drift, or the species' colonization history. Gene flow among most neighbouring colonies was not generally restricted, with one exception. These findings have important implications for the ongoing conservation management of this species.

Animals↗

Sapling structure and regeneration strategy in 18 Shorea species co-occurring in a tropical rainforest.

BACKGROUND AND AIMS: Inevitable trade-offs in structure may be a basis for differentiation in plant strategies. Juvenile trees in different functional groups are characterized by specific suites of structural traits such as crown architecture and biomass distribution. The relationship between juvenile tree structure and function was tested to find out if it is robust among functionally and taxonomically similar species of the genus Shorea that coexist sympatrically in a tropical rain forest in Borneo. METHODS: The sapling structures of 18 species were compared for standardized dry masses of 5 and 30 g. Pairwise simple correlation and multiple correlation patterns among structural traits of juveniles (0.1-1.5 m in height) of 18 Shorea species were examined using Pearson's correlation and principal component analysis (PCA), respectively. The correlation was then tested between the PCA results and three indices of shade tolerance: the net photosynthetic rate, the wood density of mature trees and seed size. KEY RESULTS: The structural variation in saplings of the genus Shorea was as large as that found in sets of species with much more diverse origins. The PCA showed that both crown architecture and allocation to leaves are major sources of variation in the structures of the 18 species investigated. Of these two axes, allocation to leaves was significantly correlated with wood density and showed a limited correlation with photosynthetic rate, whereas crown architecture was significantly correlated to seed size. CONCLUSIONS: Overall, the results suggest that an allocation trade-off between leaves and other organs, which co-varied with wood density and to a certain extent with photosynthetic capacity, accounts for the difference in shade tolerance among congeneric, functionally similar species. In contrast, the relationship between the architecture and regeneration strategy differed from the pattern found between functional groups, and the function of crown architecture was ambiguous.

Adaptation, Physiological↗

Biochemical and immunohistochemical analysis of pectic polysaccharides in the cell walls of Arabidopsis mutant QUASIMODO 1 suspension-cultured cells: implications for cell adhesion.

Mutation in the Arabidopsis thaliana QUASIMODO 1 gene (QUA1), which encodes a putative glycosyltransferase, reduces cell wall pectin content and cell adhesion. Suspension-cultured calli were generated from roots of wild-type (wt) and qua1-1 A. thaliana plants. The altered cell adhesion phenotype of the qua1-1 plant was also found with its suspension-cultured calli. Cell walls of both wt and qua1-1 calli were analysed by chemical, enzymatic and immunohistochemical techniques in order to assess the role of pectic polysaccharides in the mutant phenotype. Compared with the wt, qua1-1 calli cell walls contained more arabinose (23.6 versus 21.6 mol%), rhamnose (3.1 versus 2.7 mol%), and fucose (1.4 versus 1.2 mol%) and less uronic acid (24.2 versus 27.6 mol%), and they were less methyl-esterified (DM: 22.9% versus 30.3%). When sequential pectin extraction of calli cell walls was performed, qua1-1 water-soluble and chelator-soluble extracts contained more arabinose and less uronic acid than wt. Water-soluble pectins were less methyl-esterified in qua1-1 than in wt. Chelator-soluble pectins were more acetyl-esterified in qua1-1. Differences in the cell wall chemistry of wt and mutant calli were supported by a reduction in JIM7 labelling (methyl-esterified homogalacturonan) of the whole wall in small cells and particularly by a reduced labelling with 2F4 (calcium-associated homogalacturonan) in the middle lamella at tricellular junctions of large qua1-1 cells. Differences in the oligosaccharide profile obtained after endopolygalacturonase degradation of alkali extracts from qua1-1 and wt calli indicated variations in the structure of covalently bonded homogalacturonan. About 29% more extracellular polymers rich in pectins were recovered from the calli culture medium of qua1-1 compared with wt. These results show that perturbation of QUASIMODO 1-1 gene expression in calli resulted in alterations of homogalacturonan content and cell wall location. The consequences of these structural variations are discussed with regard to plant cell adhesion.

Alkalies↗

Phospholipase A2 from cobra (Naja naja naja) venom. Primary structure and subspecies variation.

The primary structure of phospholipase A2 of the major race of Indian cobra has been determined. Together with previous data on other subforms, it establishes subspecies variations at no less than 20 of the 119 positions in the protein. These variations are large, not only in number but in several cases also regarding properties of the residues involved. Nevertheless, all structures are compatible with largely unaltered enzyme properties.

Amino Acid Sequence↗

Hexagonal crystal structure of the A-DNA octamer d(GTGTACAC) and its comparison with the tetragonal structure: correlated variations in helical parameters.

The alternating DNA octamer d(GTGTACAC) has been grown in a novel hexagonal crystal form. The structure has been determined and refined to a 2-A resolution, with 51 water molecules. The A-DNA conformation is a variant of that observed for the tetragonal form of the same sequence (Jain et al., 1989) containing a bound spermine. The crystals belong to the space group P6(1)22, a = b = 32.40 A and c = 79.25 A, with one strand in the asymmetric unit. The new hexagonal structure was solved by rotation and translation searches in direct space and refined to a final R value of 12.7% by using 1561 unique reflections greater than 1.5 sigma (I). The electron density clearly shows that the penultimate A7 sugar had flipped into the alternative C2'-endo pucker. This dent in the molecule can be attributed to close intermolecular contacts. In contrast, in the tetragonal structure, the DNA is distorted in the central TA step, where the A5 backbone bonds C4'-C5' and O5'-P assume trans conformations. The hexagonal double helix more closely resembles the fiber diffraction A-DNA, compared to the tetragonal form. For instance, the tilt angle is higher (16 degrees vs 10 degrees), which is correlated with a larger displacement from the helix axis (3.5 vs 3.3), a lower rise per residue (2.9 vs 3.2), and a smaller major-groove width (6.1 vs 8.7), thus indicating that the variations in these global helical parameters are correlated. The propeller twist angles in both forms are higher for the G-C base pairs (15.3 degrees, 12.14 degrees) than for the A-T base pairs (10.8 degrees, 9.1 degrees), which is the reverse of the expected order. Unlike the tetragonal structure, the hexagonal crystal structure interestingly does not contain a bound spermine molecule. Our analysis reveals that the conformational differences between the tetragonal and hexagonal forms are not entirely due to the spermine binding, and crystal packing seems to play an important role.

Base Composition↗

Molecular recognition of antigenic polysaccharides: a conformational comparison of capsules from Streptococcus pneumoniae serogroup 9.

Aqueous solution conformations of three antigenic bacterial capsular polysaccharides (CPS) from S. pneumoniae serogroup 9 were determined using a combination of NMR data (NOE build-up rates and conformation-dependent chemical shifts), simulated annealing, and molecular dynamics simulations. Each polymer adopts a flexible extended ribbon conformation in solution. Conformations of structural elements shared by each PS are indistinguishable. Differences in conformations are minor and localised at the sites of structural variations; there is no evidence of long-range stabilisation of a secondary structure. It is likely that antigenic specificity of Group 9 PS is dominated by local structural variation rather than by conformational differences.

Bacterial Capsules↗

Antigenic structure and variation in an influenza virus N9 neuraminidase.

We previously determined, by X-ray crystallography, the three-dimensional structure of a complex between influenza virus N9 neuraminidase (NA) and the Fab fragments of monoclonal antibody NC-41 [P. M. Colman, W. G. Laver, J. N. Varghese, A. T. Baker, P. A. Tulloch, G. M. Air, and R. G. Webster, Nature (London) 326:358-363, 1987]. This antibody binds to an epitope on the upper surface of the NA which is made up of four polypeptide loops over an area of approximately 600 A2 (60 nm2). We now describe properties of NC-41 and other monoclonal antibodies to N9 NA and the properties of variants selected with these antibodies (escape mutants). All except one of the escape mutants had single amino acid sequence changes which affected the binding of NC-41 and which therefore are located within the NC-41 epitope. The other one had a change outside the epitope which did not affect the binding of any of the other antibodies. All the antibodies which selected variants inhibited enzyme activity with fetuin (molecular weight, 50,000) as the substrate, but only five, including NC-41, also inhibited enzyme activity with the small substrate N-acetylneuramin-lactose (molecular weight, 600). These five probably inhibited enzyme activity by distorting the catalytic site of the NA. Isolated, intact N9 NA molecules form rosettes in the absence of detergent, and these possess high levels of hemagglutinin activity (W.G. Laver, P.M. Colman, R.G. Webster, V.S. Hinshaw, and G.M. Air, Virology 137:314-323, 1984). The enzyme activity of N9 NA was inhibited efficiently by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, whereas hemagglutinin activity was unaffected. The NAs of several variants with sequence changes in the NC-41 epitope lost hemagglutinin activity without any loss of enzyme activity, suggesting that the two activities are associated with separate sites on the N9 NA head.

Antibodies, Monoclonal↗

Post-translational modifications of meningococcal pili. Identification of common substituents: glycans and alpha-glycerophosphate--a review.

Neisseria meningitidis elaborate filamentous adhesins, pili or fimbriae, which belong to the type-4 structural group of pili also found on other bacterial pathogens such as Neisseria gonorrhoeae, Pseudomonas aeruginosa, Moraxella bovis and Dichelobacter nodosus. Meningococcal pili readily undergo structural variations which arise as a result of inter- and intra-genomic recombinational events. Structural variations often result in variations in bacterial adhesion mediated by pili. Studies on structure/function relationship of meningococcal pili have shown that pili are post-translationally modified and contain unusual covalently-linked substituents. The presence of glycans was shown by the use of specific carbohydrate labelling, chemical deglycosylation and by introducing galE mutations; the latter studies confirmed the presence of galactose on pili. Mass spectrometric and other analysis of pilin-derived tryptic peptides and linked substituents were used to determine the structure of an unusual O-linked trisaccharide, Gal beta1-4 Gal alpha1-3[2,4-diacetamido-2,4,6-trideoxyhexose]. Similar studies have also identified, perhaps a unique substituent, alpha-glycerophosphate, which is attached to Ser93 by a phosphodiester linkage.

Amino Acid Sequence↗

Morphology of the mandibular fossa and inclination of the articular eminence in patients with internal derangement and in symptom-free volunteers.

OBJECTIVE: The purpose of this study was to evaluate temporomandibular joint morphology and to compare possible structural variations in the temporomandibular joint anatomy of symptomatic anterior disk displacement patients with possible structural variations in the temporomandibular joint anatomy of symptom-free volunteers. STUDY DESIGN: Fifty-six symptomatic patients and 25 symptom-free volunteers were included in this study. All subjects had bilateral high-resolution magnetic resonance imaging scans performed in the sagittal (closed and open) positions. Disk positions were evaluated with these images, and the patients were accordingly classified into 4 diagnostic groups. The angulation between the Frankfort horizontal plane and the posterior slope of the articular eminence, as well as the width and depth of the glenoid fossa and the articular tuberculum, were automatically measured with the aid of a computer. RESULTS: The Mann-Whitney U test demonstrated significant differences in the angular and linear values obtained in disk displacement with reduction patients in comparison with the values obtained in patients with disk displacement without reduction and in symptom-free volunteers. CONCLUSION: It is proposed that a steeper posterior slope and higher tuberculum articulaire are predisposing factors for the development of disk displacement with reduction. Flattening of the eminence may progress in time, leading to the onset of disk displacement without reduction.

Adult↗

Synthesis and transfection properties of novel non-toxic monocationic lipids. Variation of lipid anchor, spacer and head group structure.

This report describes the synthesis and the transfection properties of novel monocationic non-toxic lipids. We have carried out structural variations in all three units of the transfection lipid, the lipid anchor, the spacer moiety and the positively charged head group. Our results lead to the conclusion that systematic modification of structural subunits is a promising way to enhance the transfection efficiency.

Animals↗

Muscarinic properties of compounds related to arecaidine propargyl ester.

A series of new analogues of the arecaidine propargyl ester (CAS 35516-99-5), APE, 1a) with alcohols consisting of 4 or 5 carbon atoms were investigated at muscarinic receptor subtypes. The muscarinic activity of the quaternary and tertiary salts of the APE-related compounds were assayed on the isolated guinea-pig ileum (M3 receptor subtype) and guinea-pig left atria (M2 receptor subtype) as well as on rabbit isolated vas deferens (M1 receptor subtype). The structural variations made in the APE molecule, replacing the triple bond in the ester side chain with structures such as double bond, an allene moiety, a single bond, a cyclopropyl group or two triple bonds should alter the selectivity and potency in favour of the M2 subtype. Enhanced, though modest, selectivity for M2 receptors was achieved with the 2-butynyl ester 2a. The other structural variations resulted in a loss of potency, but not necessarily of efficacy.

Animals↗

The acute phase response of mouse liver. Genetic analysis of the major acute phase reactants.

We have examined changes in translatable liver mRNAs during the acute phase response in several inbred mouse strains. Induction of mRNAs for the known acute phase reactants serum amyloid A, hemopexin, haptoglobin, and alpha 1-acid glycoprotein was observed. Two alpha 1-acid glycoproteins, termed AGP-1 and AGP-2, differing in size and charge, were found in all mice and appear to derive from distinct yet closely related mRNAs. Polymorphism in the structure of AGP-1 among strains was used to map the structural gene, Agp-1, to chromosome 4 near the b locus. Structural variation for serum amyloid A enabled mapping its structural gene, S alpha alpha, to chromosome 7, near Gpi-1. A wild-derived population of mice, Mus spretus, contains several variations of interest, including structural variations in many acute phase proteins and a putative regulatory variation specific to AGP-1. Further analysis of these genetic variants should provide novel insights into the acute phase response and the factors that mediate it.

Animals↗

Genetic variation in two bone-related proteins: is there an association with bone mineral density or skeletal size in postmenopausal women?

In an effort to determine if structural variation in proteins important in bone metabolism might influence bone mineral density (BMD) and thus be a determinant of susceptibility to osteoporosis in older women, the authors typed a group of 258 non-Black women (age 65-90) participating in the Study of Osteoporotic Fractures (SOF) for two polymorphic bone-related proteins, group specific component (Gc), also known as vitamin D-binding protein, and alpha 2HS glycoprotein (AHSG). These two proteins exhibit common structural variation in populations that can be detected by isoelectric focusing/immunoblotting of serum. An important function of Gc is the binding, solubilization, and transport of vitamin D sterols in the bloodstream while AHSG is a glycoprotein constituent of calcified cortical bone matrix. There are six common phenotypes of Gc and four of AHSG. Using Gc or AHSG phenotypes as categorical variables, statistical analyses were done to determine if bone mineral density of the proximal or distal radius or calcaneus differed by phenotype. Neither Gc nor AHSG phenotype demonstrated a statistically significant relationship with BMD at any site. Adjustments for age and degree of obesity did not substantively affect these results. Subsequent analyses to determine if phenotype of either of these proteins was associated with variables related to skeletal size showed an association of AHSG with height (P less than .02). This may indicate that AHSG phenotype is related to postmenopausal loss of height, or it may be a chance statistical finding.

Aged↗

Variations in structural and functional changes of stallion spermatozoa in response to calcium ionophore A23187.

Three experiments were conducted to assess the structural and functional changes of stallion spermatozoa in response to the calcium ionophore A23187, and to determine individual variation between stallions. In Experiment 1, changes in the acrosome of spermatozoa exposed to 7.14 microM A23187 for fixed times between 0 and 120 min were examined. There was a steady increase with time in the number of spermatozoa undergoing the acrosome reaction although the rate of increase differed between stallions. Sperm motility decreased sharply when incubation was extended beyond 30 min. In Experiment 2, the ability of ionophore-treated spermatozoa to penetrate zona-free hamster eggs was tested. Percent penetration rates were 75, 50, 28, 27 and 15 for the 5 stallions although the number of swollen sperm heads per penetrated egg (1.7-2.5) did not differ significantly between the stallions. In Experiment 3, the ability of stallion spermatozoa to fertilize zona-intact follicular horse eggs matured in vitro was tested. Semen samples from the 2 stallions that provided the highest and lowest percent acrosome-reacted spermatozoa in Experiment 1, and the highest and lowest penetration rates in Experiment 2, were separated from seminal plasma and treated with 5 microM A23187 for 10 min. The spermatozoa were then washed once and co-incubated with the eggs at 38.5 degrees C for 12-16 h. Swollen sperm heads with associated tails from 1 stallion were found in 8 of 46 eggs fixed after 12-16 h incubation, whereas the corresponding figure for the other stallion was 0/30. It was concluded that considerable individual variation occurs between stallions in the morphological and functional changes exhibited by their spermatozoa in response to treatment with ionophore A23187.

Animals↗