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PubMed2005

Spatial structure of genetic variation and primary succession in the pioneer tree species Antirhea borbonica on La Réunion.

In habitats where colonization and extinction are recurrent, the distribution of gene frequencies among patches of suitable habitat may reflect the age structure of different populations. In this study, we quantify population genetic structure for a pioneer tree species, Antirhea borbonica, in a chrono-sequence of primary succession on the lava flows of the Piton de La Fournaise volcano (La Réunion). Using microsatellite loci and amplified fragment length polymorphism (AFLP) markers, we quantified genetic variation within and among populations for early- and late-succession populations in a landscape where extinction and recolonization are recurrent (the 'Grand Brûlé') and for late-succession populations in a more stable landscape. This study produced three main results. First, we detected no evidence that founder events increase genetic differentiation among colonizing populations; F(ST) values among early- and among late-succession populations were similar. Second, we found no evidence for isolation by distance; genetic distance was not correlated with spatial distance within and among populations. Third, F(IS) values are consistently high in all populations, despite the fact that A. borbonica populations are functionally close to dioecy and thus expected to have an outcrossing mating system. Multiple colonization events from different sources may limit differentiation among young populations and spatial isolation may enhance differentiation among late-succession populations. Ecological processes acting during colonization may create the conditions for spatial aggregation within pioneer populations, and thus contribute to the high F(IS) values.

DNA Primers↗
PubMed2000

Reconciling patterns of genetic variation with stream structure, earth history and biology in the Australian freshwater fish Craterocephalus stercusmuscarum (Atherinidae).

We examined the consequences of barriers, stream architecture and putative dispersal capability on levels of genetic differentiation among populations of the freshwater fish Craterocephalus stercusmuscarum. Seven polymorphic allozyme loci and sequences of a 498-bp fragment of the ATPase 6 mitochondrial DNA (mtDNA) gene were used to assess patterns of genetic variation among 16 populations from upland and lowland streams of five drainages in northern Queensland, Australia. Concordant patterns at both genetic markers revealed that there were significant levels of genetic subdivision among all populations, while an analysis of molecular variation showed that the distribution of genetic diversity was not consistent with contemporary drainage structure. There were reciprocally monophyletic mtDNA clades and fixed or large frequency differences at allozyme loci either side of instream barriers such as waterfalls. This implied barriers were effective in restricting gene flow between upland and lowland populations separated by waterfalls. However, there were two genetically distinct groups in upland areas, even within the same subcatchment, as well as high levels of genetic subdivision among lowland populations, suggesting barriers alone do not explain the patterns of genetic diversity. The data revealed a complex phylogeographic pattern, which we interpreted to be the result of one or more invasion events of independent lineages to different sections of each drainage, possibly mediated by well documented geomorphological changes. Our results highlight the importance of earth structure and history in shaping population genetic structure in stream organisms where dispersal capability may be limited, and reveal that the contemporary structure of drainages is not necessarily a good indicator of genetic relationships among populations.

Adenosine Triphosphatases↗
PubMed1984

A morphometric study of the 24-hour variations in subcellular structures of rat pancreatic acinar cells during the periweaning period.

Pancreatic acinar cells of rats obtained before (21 days of age) and after (31 and 42 days) weaning were morphometrically examined at six evenly spaced times during 24 h. Morphometric analysis demonstrated clear-cut variations in the average volume of the cell and nucleus, the incidence of binucleate acinar cells, and the volume and numerical densities of various cytoplasmic organelles during 24 h, at each stage. The daily mean values and variation of these parameters at 21 days clearly differed from those at 31 and 42 days. In particular, changes in the volume densities of rER and zymogen granules were bimodal at 21 days, whereas they were unimodal at 31 and 42 days. Moreover, some parameters also differed between 31 and 42 days, the main difference being an 8 h time shift in the variation curves of the volume densities of rER and zymogen granules. These findings indicate that morphometric analysis of the subcellular structures of pancreatic acinar cells during 24 h can be used to determine their developmental stage.

Age Factors↗
PubMed1992

Dimensional variation of craniofacial structures in relation to changing masticatory-functional demands.

A reduction in masticatory stress has been an important factor in the evolution of the human skull. Similarly, the recent increase in the occlusal variation has been related to a change in masticatory activity. The present study investigates short-term variation in craniofacial dimensions by examining cephalometrically two Finnish samples, one exposed to a hard and the other to a soft diet. The samples comprised 32 skulls, derived from the 16th and 17th centuries, and 50 living individuals. Out of 18 dimensions measured, 12 showed only non-significant differences between the samples. In the present-day sample, the cranial length and the anterior cranial base were significantly longer, and the upper incisors segment significantly higher. In the skull sample, the posterior facial height, the height of the mandibular ramus, and the antero-posterior width of the pharynx were significantly larger. The results suggest that hard diet, which requires more chewing force and time, promotes vertical growth of the ramus and anterior translocation of the maxilla. The greater posterior face height and greater height of ramus are in accordance with the earlier finding that the mandible shows more anterior growth rotation in an attritive environment. These findings support the hypothesis that the growth of the craniofacial skeleton is regulated by masticatory stress. It is suggested that both the dimensional changes and the lack of dental attrition may have contributed to the higher occlusal variation of modern individuals.

Adult↗
PubMed2002

Structural and functional variation within the alanine-rich repetitive domain of streptococcal antigen I/II.

Members of the antigen I/II family of cell surface proteins are highly conserved, multifunctional adhesins that mediate interactions of oral streptococci with other oral bacteria, with cell matrix proteins (e.g., type I collagen), and with salivary glycoproteins, e.g., gp340. The interaction of gp340 (formerly designated salivary agglutinin) with Streptococcus mutans requires an alanine-rich repetitive domain (A region) of antigen I/II that is highly conserved in all members of this family of proteins. In this report, we show that the A regions from the two Streptococcus gordonii M5 antigen I/II proteins (SspA and SspB) interact differently with the salivary gp340 glycoprotein and appear to be structurally distinct. Recombinant polypeptides encompassing the A region of SspA or from a highly related S. mutans antigen I/II protein (SpaP) competitively inhibited the interaction of gp340 with intact S. gordonii and S. mutans cells, respectively. In contrast, an A region polypeptide from SspB was inactive, and furthermore, it did not bind to purified gp340 in vitro. Circular dichroism spectra suggested that all three polypeptides were highly alpha-helical and may form coiled-coil structures. However, the A region of SspB underwent a conformational change and exhibited reduced alpha-helical structure at pH 8.5, whereas the A region polypeptides from SspA and SpaP were relatively stable under these conditions. Melt curves also indicated that at physiological pH, the A region of SspB lost alpha-helical structure more rapidly than that of SspA or SpaP when the temperature was increased from 10 to 40 degrees C. Furthermore, the SspB A region polypeptide denatured completely at a temperature that was 7 to 9 degrees C lower than that required for the A region polypeptide of SspA or SpaP. The full-length SspB protein and the three A region peptides migrated in native gel electrophoresis and column chromatography with apparent molecular masses that were approximately 2- to 2.5-fold greater than their predicted molecular masses. However, sedimentation equilibrium ultracentrifugation data showed that the A region peptides sedimented as monomers, suggesting that the peptides may form nonglobular intramolecular coiled-coil structures under the experimental conditions used. Taken together, our results suggest that the A region of SspB is less stable than the corresponding A regions of SspA and SpaP and that this structural difference may explain, at least in part, the functional variation observed in their interactions with salivary gp340.

Adhesins, Bacterial↗
PubMed1982

Structural and numerical variations of the carbohydrate moiety of immunoglobulin G.

Oligosaccharide patterns obtained from human IgG by hydrazinolysis were fairly constant from sample to sample. In contrast, a variety of oligosaccharide patterns were obtained from IgG myeloma proteins. Structural analysis of each oligosaccharide by sequential exoglycosidase digestion and methylation studied indicated that the different patterns of IgG myeloma proteins are produced by different degrees of incompleteness of the formation of a single sugar chain: Sia alpha 2 leads to Gal beta 1 leads to 4GlcNAc beta 1 leads to 2 Man alpha 1 leads to 6(Sia alpha 2 leads to Gal beta 1 leads to 4GlcNAc beta 1 leads to Man alpha 1 leads to 3)(GlcNAc beta 1 leads to 4)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAcOT.

Acetylglucosaminidase↗
PubMed2002

General aspects of peptide selectivity towards lipid bilayers and cell membranes studied by variation of the structural parameters of amphipathic helical model peptides.

Model compounds of modified hydrophobicity (Eta), hydrophobic moment (mu) and angle subtended by charged residues (Phi) were synthesized to define the general roles of structural motifs of cationic helical peptides for membrane activity and selectivity. The peptide sets were based on a highly hydrophobic, non-selective KLA model peptide with high antimicrobial and hemolytic activity. Variation of the investigated parameters was found to be a suitable method for modifying peptide selectivity towards either neutral or highly negatively charged lipid bilayers. Eta and mu influenced selectivity preferentially via modification of activity on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) bilayers, while the size of the polar/hydrophobic angle affected the activity against 1-palmitoyl-2-oleoylphosphatidyl-DL-glycerol (POPG). The influence of the parameters on the activity determining step was modest in both lipid systems and the activity profiles were the result of the parameters' influence on the second less pronounced permeabilization step. Thus, the activity towards POPC vesicles was determined by the high permeabilizing efficiency, however, changes in the structural parameters preferentially influenced the relatively moderate affinity. In contrast, intensive peptide accumulation via electrostatic interactions was sufficient for the destabilization of highly negatively charged POPG lipid membranes, but changes in the activity profile, as revealed by the modification of Phi, seem to be preferentially caused by variation of the low permeabilizing efficiency. The parameters proved very effective also in modifying antimicrobial and hemolytic activity. However, their influence on cell selectivity was limited. A threshold value of hydrophobicity seems to exist which restricted the activity modifying potential of mu and Phi on both lipid bilayers and cell membranes.

Anti-Bacterial Agents↗
PubMed1986

Computer-aided studies of the structure-activity relationships between the structure of some steroids and their antiinflammatory activity.

The relationship between variation in structure and variation in antiinflammatory activity was investigated for 125 steroids whose antiinflammatory activity had previously been determined by using the McKenzie-Stoughton human vasoconstrictor assay. Eighty-eight of the compounds were used in the training stages of analysis. A two-class problem was developed by classifying the compounds as low-to-no potency (37 compounds) or potent-to-very potent (51 compounds) on the basis of their activity relative to that of hydrocortisone butyrate. Thirty-eight different structural variations occurred at six different sites on the steroid nucleus. These variations were coded by a total of 10 descriptors--three indicator descriptors and seven descriptors that coded for the lipophilicity of the substituents at specific sites of variation. Linear discriminant analysis, principal components plots, K nearest neighbor analysis, and statistical measurements of class separation all confirmed that the more potent compounds existed in a region of the data space different from the less potent compounds. This structure-activity relationship was applied to the prediction of the activities of 37 compounds that were not used in the preliminary analysis with good results.

Anti-Inflammatory Agents↗
PubMed1979

A fine structural study of variations in protein concentration in lacteals during compression and relaxation.

The ratios of plasma proteins and ferritin (introduced into the gut) were determined between the jejunal lacteals and the interstitial channels in puppies. This was done by fine structural densitometry and the counting of molecules, respectively. In the normal state this ratio was approximately 2. In portions of tissue whose smooth muscle had been relaxed by atropine the ratio was approximately 1; in others, where the muscle had been contracted by Carbacol, it was approximately 3. These latter correspond approximately to the filling-phase and the emptying-phase of the initial lymphatic cycle, respectively. Thus the evidence was strengthened for an hypothesis, which holds that the filling is caused by the high effective colloidal osmotic pressure of the concentrated lymph.

Animals↗
PubMed2003

Allelic variation of MHC structure alters peptide ligands to induce atypical partial agonistic CD8+ T cell function.

T cell receptors recognize small changes in peptide ligands leading to different T cell responses. Here, we analyzed a panel of HLA-A2-Tax11-19 reactive T cell clones to examine how small allelic variations of MHC molecules could alter the functional outcome of antigen recognition. Similar to the effects induced by antigenic altered peptide ligands, weak or partial agonistic T cell functions were identified in individual T cell clones with the recognition of MHC-altered peptide ligands (MAPLs). Interestingly, one subtype of HLA-A2 molecules induced an unusual type of partial agonistic function; proliferation without cytotoxicity. Modeling of crystallographic data indicated that polymorphic amino acids in the HLA-A2 peptide binding groove, especially the D-pocket, were responsible for this partial agonism. Reciprocal mutations of the Tax peptide side chain engaging the D-pocket indeed restored the agonist functions of the MHC-peptide complex. Whereas early intracellular signaling events were not efficiently induced by these MAPLs, phosphorylated c-Jun slowly accumulated with sustained long-term expression. These data indicate that MAPLs can induce atypical partial agonistic T cell function through structural and biochemical mechanisms similar to altered peptide ligands.

Alleles↗
PubMed2003

[Characterization of 5S rRNA gene sequence and secondary structure in gymnosperms].

In higher plants the primary and the secondary structures of 5S ribosomal RNA gene are considered highly conservative. Little is known about the 5S rRNA gene structure, organization and variation in gyimnosperms. In this study we analyzed sequence and structure variation of 5S rRNA gene in Pinus through cloning and sequencing multiple copies of 5S rDNA repeats from individual trees of five pines, P. bungeana, P. tabulaeformis, P. yunnanensis, P. massoniana and P. densata. Pinus bungeana is from the subgenus Strobus while the other four are from the subgenus Pinus (diploxylon pines). Our results revealed variations in both primary and secondary structure among copies of 5S rDNA within individual genomes and between species. 5S rRNA gene in Pinus is 120 bp long in most of the 122 clones we sequenced except for one or two deletions in three clones. Among these clones 50 unique sequences were identified and they were shared by different pine species. Our sequences were compared to 13 sequences each representing a different gymnosperm species, and to six sequences representing both angiosperm monocots and dicots. Average sequence similarity was 97.1% among Pinus species and 94.3% between Pinus and other gymnosperms. Between gymnosperms and angiosperms the sequence similarity decreased to 88.1%. Similar to other molecular data, significant sequence divergence was found between the two Pinus subgenera. The 5S gene tree (neighbor-joining tree) grouped the four diploxylon pines together and separated them distinctly from P. bungeana. Comparison of sequence divergence within individuals and between species suggested that concerted evolution has been very weak especially after the divergence of the four diploxylon pines. The phylogenetic information contained in the 5S rRNA gene is limited due to its shorter length and the difficulties in identifying orthologous and paralogous copies of rDNA multigene family further complicate its phylogenetic application. Pinus densata is a diploid hybrid between P. tabulaeformis and P. yunnanensis. Its 5S rDNA composition is consistent with its hybrid origin. 5S rRNA of all gymnosperms published so far could be folded into a general secondary structure. Variation in this secondary structure was detected among species. About 55% of the 120 bp nucleotide positions was variable, in which 68% was on stem regions. Nevertheless, the positions at the end of the stems and those adjacent to loops are conserved. Their stability directly determines the size of the loops. Some mutations such as compensatory base-pair substitutions, and G-U pairing could be regarded as mechanisms for maintaining a stable secondary structure. The loops of the secondary structure are also relatively conserved. It seems that stable helices are necessary for the function of the gene. The conserved nucleotides in the loops are probably involved in the interaction with proteins and/or RNAs or with other nucleotide in the formation of the tertiary structure. However, unlike other reports, Loop E was found quite mutable among pines. These variations together with those on stems might be caused by the presence of pseudogenes among our clones. A preliminary evaluation indicates that only seven of 50 unique sequences are potentially functional genes.

Base Sequence↗
PubMedDate not supplied

[Variations and valve structure of the truncal femoro-popliteal system].

Study of valves is inseparable from that of the main veins in which they are located. While a modal femoro-popliteal system, satellite to the arterial system, is by far the commonest, major variations are seen in approximately 10% of cases. Each main collecting vein has its specificity, according to its width, the course which it follows and whether or not there is a satellite wide calibre artery. Additional features include the chief affluents which its receives, wavering of its course, the supple or rigid perivascular environment and the proximity of large muscle masses. All these features play a role in the quality of drainage, in particular during exercise, and in anti-reflux function. In practice, variations come down to two broad possibilities: the single collector, sometimes made up of several different embryological segments, resulting in a hybrid vessel and an aberrant course, either axial, satellite to the sciatic nerve, or profunda femoris, satellite to the shaft of the femur. Doubling (bifid or by bifurcation) opens up an additional channel, either parallel or divergent, which considerably modifies the conditions of venous return. A lesion affecting one branch only, e.g. a solitary thrombus, may have no clinical manifestations and marking if collectors during imaging. The topography of the valves of the main veins tends to be fairly fixed. They are preferentially located proximal to the main confluents, to winding parts of the course of the vessel, or at certain hemodynamic levels which vary little from one individual to another. An attempt is made at nomenclature, classification and topography. The chief feature, the terminal valve of the lower limb, is located most often at the femoral ring. It alone is capable of opposing the long cavo-iliac reflux caused by effort. Analysis of retrograde phlebography films with caval occlusion shows that reflux is not directly exerted on the valve. The point of interruption is high, in the terminal portion of the external iliac vein. This hemodynamic barrage is purely functional. When there is incontinence of the terminal valve varying degrees of reflux diffusely affect the femoral axis. At the same time, there is regurgitation of contrast medium into the visceral areas of the true pelvis, normally sealed off. This coupling between anti-reflux function of the lim and that of the pelvis is one of the unexpected aspects of valve activity.

Blood Circulation↗
PubMed2004

Determination of sequence variation and haplotype structure for the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes: investigation of role in pubertal timing.

Because GnRH and its receptor (GnRHR) are pivotal regulators of the reproductive endocrine axis and mutations in GNRHR lead to hypogonadotropic hypogonadism, we investigated whether genetic variation in GNRHR or GNRH1 affects pubertal timing in the general population. To screen for missense mutations in these genes that might affect pubertal timing, we resequenced the coding regions of these genes in 48 probands with late but otherwise normal pubertal development. No missense variants were found in either gene, except for a previously identified single nucleotide polymorphism (SNP) in GNRH1 that was not associated with late pubertal development. To search for common variants that might affect pubertal timing, we took a haplotype-based association approach. To identify common haplotypes in these genes, we genotyped 41 SNPs in DNA from commercially available European-derived multigenerational pedigrees and participants in a multiethnic cohort (MEC). Two blocks of strong linkage disequilibrium were identified that spanned GNRHR and one was identified spanning GNRH1; within each block, more than 80% of chromosomes carried one of a few common haplotypes. A set of haplotype-tagging SNPs that mark these common haplotypes in all five ethnic groups within the MEC were defined and used to perform association studies among 125 trios (probands with late pubertal development and their parents) and 506 women from the MEC who had early (menarche < 11 yr of age, n = 216) or late (menarche > or = 15 yr of age, n = 290) pubertal development. Three SNPs in GNRHR showed modest association with late pubertal development in the trios; among the 506 women, a different SNP was associated with late menarche, and one rare haplotype was associated with early age of menarche. All of the observed associations were relatively modest and only nominally statistically significant; replication is needed to determine their validity. We conclude that genetic variation in GNRH1 and GNRHR is not likely to be a substantial modulator of pubertal timing in the general population.

Age Factors↗
PubMed1999

Population structure and genetic variation of european wild rabbits (Oryctolagus cuniculus) in east anglia

The European wild rabbit (Oryctolagus cuniculus) is an introduced species in Britain, and populations have been profoundly influenced by both man and disease. In stable environmental conditions, distinct social behaviour is observed, and this social structure leads to significant genetic structuring at the intrapopulation level. In this study, European wild rabbits were sampled from 17 sites across the East Anglian region of Britain and genotyped with nine microsatellite loci. Genotypical proportions deviated significantly from Hardy-Weinberg equilibrium, reflecting a degree of population subdivision and non-random mating. Several estimates of measures of population genetic structure revealed that populations are genetically distinct and have small effective population sizes. These distinctive properties are seen to be the combined effects of the social structure and random drift acting on bottlenecked populations after myxomatosis. It is concluded that the genetic structure seen in rabbit populations today is unlikely to reflect historical structuring present before myxomatosis, but that it results from recent events.

Journal Article↗
PubMed2003

Structural basis for variation in adenovirus affinity for the cellular coxsackievirus and adenovirus receptor.

The majority of adenovirus serotypes can bind to the coxsackievirus and adenovirus receptor (CAR) on human cells despite only limited conservation of the amino acid residues that comprise the receptor-binding sites of these viruses. Using a fluorescence anisotropy-based assay, we determined that the recombinant knob domain of the fiber protein from adenovirus serotype (Ad) 2 binds the soluble, N-terminal domain (domain 1 (D1)) of CAR with 8-fold greater affinity than does the recombinant knob domain from Ad12. Homology modeling predicted that the increased affinity of Ad2 knob for CAR D1 could result from additional contacts within the binding interface contributed by two residues, Ser408 and Tyr477, which are not conserved in the Ad12 knob. Consistent with this structural model, substitution of serine and tyrosine for the corresponding residues in the Ad12 knob (P417S and S489Y) increased the binding affinity by 4- and 8-fold, respectively, whereas the double mutation increased binding affinity 10-fold. X-ray structure analysis of Ad12 knob mutants P417S and S489Y indicated that both substituted residues potentially could form additional hydrogen bonds across the knob-CAR interface. Structural changes resulting from these mutations were highly localized, implying that the high tolerance for surface variation conferred by the stable knob scaffold can minimize the impact of antigenic drift on binding specificity and affinity during evolution of virus serotypes. Our results suggest that the interaction of knob domains from different adenovirus serotypes with CAR D1 can be accurately modeled using the Ad12 knob-CAR D1 crystal structure as a template.

Adenoviridae↗
PubMed2000

Neocortical malformation as consequence of nonadaptive regulation of neuronogenetic sequence.

Variations in the structure of the neocortex induced by single gene mutations may be extreme or subtle. They differ from variations in neocortical structure encountered across and within species in that these "normal" structural variations are adaptive (both structurally and behaviorally), whereas those associated with disorders of development are not. Here we propose that they also differ in principle in that they represent disruptions of molecular mechanisms that are not normally regulatory to variations in the histogenetic sequence. We propose an algorithm for the operation of the neuronogenetic sequence in relation to the overall neocortical histogenetic sequence and highlight the restriction point of the G1 phase of the cell cycle as the master regulatory control point for normal coordinate structural variation across species and importantly within species. From considerations based on the anatomic evidence from neocortical malformation in humans, we illustrate in principle how this overall sequence appears to be disrupted by molecular biological linkages operating principally outside the control mechanisms responsible for the normal structural variation of the neocortex. MRDD Research Reviews 6:22-33, 2000.

Algorithms↗

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