Finite element simulation of the behavior of the periodontal ligament: A validated nonlinear contact model

Due to its significance in tooth movement, the stress/deformation field of periodontium and the alveolar bone remodeling process, periodontal ligament (PDL) cannot be excluded from the studies investigating dental biomechanics regarding its excessive deformability. Therefore, many analytical and numerical researches are carried out to simulate its response and to create a constitutive model via experiments intending to discover the material properties of PDL. The aim of this study is to formulate a user specified contact model that can be used in conjunction with finite element (FE) software and reflects PDL’s influence on neighboring structures based on the currently available information, without requiring an actual volumetric finite element mesh of ligament. The results show good agreement with available experimental tooth mobility data. Smooth stress fields are obtained on the tooth root and alveolar bone, which is a significant aspect in bone-remodeling studies. The advantage of simulating PDL as a contact model at the interface of tooth root and the alveolar process instead of a solid-meshed FE model with poor geometric morphology and/or very dense mesh is expected to save pre/post-processing workforce, to increase the accuracy and to contribute to the smoothness of interface stress distributions.     

Triploidy in a sexually dimorphic passerine provides new evidence for the effect of the W chromosome on secondary sexual traits in birds

In birds, there are two main models for the determination of sex: the ‘Z Dosage’ model in which the number, or dose, of Z chromosomes determines sex, and the ‘Dominant W’ model which argues that a specific gene in the W chromosome may influence Z gene expression and determine sex. The best evidence for W determination of sex comes from birds with 2 copies of the Z chromosome paired with a single W (e.g. ZZW) which are nonetheless females. Here, we expand the species where such a mechanism may operate by reporting a case of a triploid Neotropical passerine bird with sexually dimorphic plumage, the São Paulo marsh antwren Formicivora paludicola. Evidence from 17 autosomal unlinked microsatellite loci, and CHD1 sex‐linked locus, indicate that this individual is a 3n ZZW triploid with intermediate plumage pattern. This example expands our knowledge of sex determination mechanisms in birds by demonstrating that both the W and the two Z chromosomes affect the expression of morphological secondary sexual traits in a non‐galliform bird.     

Electrical properties of frog skeletal muscle fibers interpreted with a mesh model of the tubular system.

This paper presents the construction, derivation, and test of a mesh model for the electrical properties of the transverse tubular system (T-system) in skeletal muscle. We model the irregular system of tubules as a random network of miniature transmission lines, using differential equations to describe the potential between the nodes and difference equations to describe the potential at the nodes. The solution to the equations can be accurately represented in several approximate forms with simple physical and graphical interpretations. All the parameters of the solution are specified by impedance and morphometric measurements. The effect of wide circumferential spacing between T-system openings is analyzed and the resulting restricted mesh model is shown to be approximated by a mesh with an access resistance. The continuous limit of the mesh model is shown to have the same form as the disk model of the T-system, but with a different expression for the tortuosity factor. The physical meaning of the tortuosity factor is examined, and a short derivation of the disk model is presented that gives results identical to the continuous limit of the mesh model. Both the mesh and restricted mesh models are compared with experimental data on the impedance of muscle fibers of the frog sartorius. The derived value for the resistivity of the lumen of the tubules is not too different from that of the bathing solution, the difference probably arising from the sensitivity of this value to errors in the morphometric measurements.     

Karyological investigations of populations of the lizard Zootoca vivipara (Juaquin, 1787) from the Baltic Sea basin (western region of Russia)

Populations of the lizard Zootoca vivipara (Juaquin, 1787) (Lacertidae, Sauria) from Western and Central Europe are poorly differentiated in morphology. However, they differ from each other by several karyotype markers and their reproductive mode (oviparous and viviparous types). Here we report for the first time the results of combined investigations of Z. vivipara from Eastern Europe (the Baltic Sea basin of Western Russia). The karyotype and reproductive mode of the specimens from four previously not examined populations in Kaliningrad region have been studied. It has been shown that these lizards have viviparous mode of reproduction and their karyotypes vary on morphology of W-sex chromosomes. Females possess 2n = 35 : 32 A + Z1Z2W, with W--SV and 2n = 35 : 32 A + Z1Z2W, with W--A/ST. We have identified these populations karyologically and have first revealed that they belong to two different viviparous forms of nominative subspecies Z. v. vivipara, namely to its "western" and "Russian (eastern)" forms. These data have confirmed that the Baltic Sea basin in Eastern Europe is a zone of secondary contact of these chromosomal forms of Z. v. vivipara. The results obtained do not now allow us to speak about their sympatry, parapatry and (or) hybridization events. The results suggest that during postglasial time "western" form might colonize this region from western Europe whereas "Russian (eastern)" form might do it from Southern-Eastern Europe. It has been recommended to save the biodiversity of Z. vivipara in Kaliningrad region, namely the peripheral and very rare on vast territory of Russia "western" form and unique for western region of Russia "Russian (eastern)" form.     

The use of sparse CT datasets for auto-generating accurate FE models of the femur and pelvis

The finite element (FE) method when coupled with computed tomography (CT) is a powerful tool in orthopaedic biomechanics. However, substantial data is required for patient-specific modelling. Here we present a new method for generating a FE model with a minimum amount of patient data. Our method uses high order cubic Hermite basis functions for mesh generation and least-square fits the mesh to the dataset. We have tested our method on seven patient data sets obtained from CT assisted osteodensitometry of the proximal femur. Using only 12 CT slices we generated smooth and accurate meshes of the proximal femur with a geometric root mean square (RMS) error of less than 1 mm and peak errors less than 8 mm. To model the complex geometry of the pelvis we developed a hybrid method which supplements sparse patient data with data from the visible human data set. We tested this method on three patient data sets, generating FE meshes of the pelvis using only 10 CT slices with an overall RMS error less than 3 mm. Although we have peak errors about 12 mm in these meshes, they occur relatively far from the region of interest (the acetabulum) and will have minimal effects on the performance of the model. Considering that linear meshes usually require about 70-100 pelvic CT slices (in axial mode) to generate FE models, our method has brought a significant data reduction to the automatic mesh generation step. The method, that is fully automated except for a semi-automatic bone/tissue boundary extraction part, will bring the benefits of FE methods to the clinical environment with much reduced radiation risks and data requirement.     

Sex chromosome pairing and sex chromatin bodies in W-Z translocation strains of Ephestia kuehniella (Lepidoptera).

Structure and pairing behavior of sex chromosomes in females of four T(W;Z) lines of the Mediterranean flour moth, Ephestia kuehniella, were investigated using light and electron microscopic techniques and compared with the wild type. In light microscopic preparations of pachytene oocytes of wild-type females, the WZ bivalent stands out by its heterochromatic W chromosome strand. In T(W;Z) females, the part of the Z chromosome that was translated onto the W chromosome was demonstrated as a distal segment of the neo-W chromosome, displaying a characteristic non-W chromosomal chromomere-interchromomere pattern. This segment is homologously paired with the corresponding part of a complete Z chromosome. In contrast with the single ball of heterochromatic W chromatin in highly polyploid somatic nuclei of wild-type females, the translocation causes the formation of deformed or fragmented W chromatin bodies, probably owing to opposing tendencies of the Z and W chromosomal parts of the neo-W. In electron microscopic preparations of microspread nuclei, sex chromosome bivalents were identified by the remnants of electron-dense heterochromatin tangles decorating the W chromosome axis, by the different lengths of the Z and W chromosome axes, and by incomplete pairing. No heterochromatin tangles were attached to the translocated segment of the Z chromosome at one end of the neo-W chromosome. Because of the homologous pairing between the translocation and the structurally normal Z chromosome, pairing affinity of sex chromosomes in T(W;Z) females is significantly improved. Specific differences observed among T(W;Z)1-4 translocations are probably due to the different lengths of the translocated segments.     

Causal assessment of surrogacy in a meta-analysis of colorectal cancer trials

When the true end points (T) are difficult or costly to measure, surrogate markers (S) are often collected in clinical trials to help predict the effect of the treatment (Z). There is great interest in understanding the relationship among S, T, and Z. A principal stratification (PS) framework has been proposed by Frangakis and Rubin (2002) to study their causal associations. In this paper, we extend the framework to a multiple trial setting and propose a Bayesian hierarchical PS model to assess surrogacy. We apply the method to data from a large collection of colon cancer trials in which S and T are binary. We obtain the trial-specific causal measures among S, T, and Z, as well as their overall population-level counterparts that are invariant across trials. The method allows for information sharing across trials and reduces the nonidentifiability problem. We examine the frequentist properties of our model estimates and the impact of the monotonicity assumption using simulations. We also illustrate the challenges in evaluating surrogacy in the counterfactual framework that result from nonidentifiability.     

Pattern formation in development of chondrichthyan dentitions: a review of an evolutionary model

The mode of tooth development displayed in Chondrichthyans (sharks, rays and holocephalans), one of frequent tooth replacement, was possible once a dental lamina had evolved, and since 1982 this has been known as the odontode regulation theory after Reif. Today, Reif's concepts need to be transformed into those of modern biology, the crosstalk between epithelium and mesenchyme, for the regulation of timing, spacing and shape of vertebrate teeth. Although Reif's proposed ‘primordial tissue’ may be the only site of progenitor cells, to restrict odontogenic potential to time-specific sites (protogerms), as has been suggested in the sequential addition tooth (SAT) model, very little data are available. Here, his model of alternate tooth replacement files has been interpreted as an integrated tooth addition unit of two adjacent files (SAT) unit for alternate replacement of teeth, regulated by putative, precisely timed gene expression for activation and inhibition. We have provided new data on patterns of tooth succession in dentitions of extant sharks and rays to compare with those of Reif. Using a phylogeny combined from molecular and morphological data, it is suggested that the alternate tooth addition and replacement model is derived within Chondrichthyes, and diversified from single file tooth addition of the stem chondrichthyans.     

Retroposon insertions and the chronology of avian sex chromosome evolution

The vast majority of extant birds possess highly differentiated Z and W sex chromosomes. Nucleotide sequence data from gametologs (homologs on opposite sex chromosomes) suggest that this divergence occurred throughout early bird evolution via stepwise cessation of recombination between identical sex chromosomal regions. Here, we investigated avian sex chromosome differentiation from a novel perspective, using retroposon insertions and random insertions/deletions for the reconstruction of gametologous gene trees. Our data confirm that the CHD1Z/CHD1W genes differentiated in the ancestor of the neognaths, whereas the NIPBLZ/NIPBLW genes diverged in the neoavian ancestor and independently within Galloanserae. The divergence of the ATP5A1Z/ATP5A1W genes in galloanserans occurred independently in the chicken, the screamer, and the ancestor of duck-related birds. In Neoaves, this gene pair differentiated in each of the six sampled representatives, respectively. Additionally, three of our investigated loci can be utilized as universal, easy-to-use independent tools for molecular sexing of Neoaves or Neognathae.     

Triploid plover female provides support for a role of the W chromosome in avian sex determination

Two models, Z Dosage and Dominant W, have been proposed to explain sex determination in birds, in which males are characterized by the presence of two Z chromosomes, and females are hemizygous with a Z and a W chromosome. According to the Z Dosage model, high dosage of a Z-linked gene triggers male development, whereas the Dominant W model postulates that a still unknown W-linked gene triggers female development. Using 33 polymorphic microsatellite markers, we describe a female triploid Kentish plover Charadrius alexandrinus identified by characteristic triallelic genotypes at 14 autosomal markers that produced viable diploid offspring. Chromatogram analysis showed that the sex chromosome composition of this female was ZZW. Together with two previously described ZZW female birds, our results suggest a prominent role for a female determining gene on the W chromosome. These results imply that avian sex determination is more dynamic and complex than currently envisioned.     

Comparison of methods to determine the centre of resistance of teeth

In orthodontic treatment, the locations of the centre of resistance (CR) of individual teeth and the applied load system are the major determinants for the type of tooth movement achieved. Currently, CR locations have only been specified for a relatively small number of tooth specimen for research purposes. Analysing cone beam computed tomography data samples from three upper central incisors, this study explores whether the effort to establish accurate CR estimates can be reduced by (i) morphing a pre-existing simplified finite element (FE) mesh to fit to the segmented 3D tooth-bone model, and (ii) individualizing a mean CR location according to a small parameter set characterising the morphology of the tooth and its embedding. The FE morphing approach and the semi-analytical approach led to CR estimates that differ in average only 0.04 and 0.12 mm respectively from those determined by very time-consuming individual FE modelling (standard method). Both approaches may help to estimate the movement of individual teeth during orthodontic treatment and, thus, increase the therapeutic efficacy.     

Molecular evolution of the avian CHD1 genes on the Z and W sex chromosomes

Genes shared between the nonrecombining parts of the two types of sex chromosomes offer a potential means to study the molecular evolution of the same gene exposed to different genomic environments. We have analyzed the molecular evolution of the coding sequence of the first pair of genes found to be shared by the avian Z (present in both sexes) and W (female-specific) sex chromosomes, CHD1Z and CHD1W. We show here that these two genes evolve independently but are highly conserved at nucleotide as well as amino acid levels, thus not indicating a female-specific role of the CHD1W gene. From comparisons of sequence data from three avian lineages, the frequency of nonsynonymous substitutions (K(a)) was found to be higher for CHD1W (1.55 per 100 sites) than for CHD1Z (0.81), while the opposite was found for synonymous substitutions (K(s), 13.5 vs. 22.7). We argue that the lower effective population size and the absence of recombination on the W chromosome will generally imply that nonsynonymous substitutions accumulate faster on this chromosome than on the Z chromosome. The same should be true for the Y chromosome relative to the X chromosome in XY systems. Our data are compatible with a male-biased mutation rate, manifested by the faster rate of neutral evolution (synonymous substitutions) on the Z chromosome than on the female-specific W chromosome.     

Le prétendu rhinocéros de Nouvelle Calédonie est un marsupial (Zygomaturus diahotensis nov. sp.): Solution d'une énigmeet conséquences paléogéographiques

The first mammalian remain ever found in NewCaledonia is an upper tooth found by golddiggers in the Plio-Pleistocene terrace from the Diahot river. This tooth, given to the Muséum national d'Histoire naturelle (Paris) in 1876, was determined as a rhinoceros tooth and then completely forgotten. Its detailed study shows that it belongs to Zygomaturus, a large marsupial diprotodontid genus whose story is rather complicated. The Diahot tooth represents a new species of Zygomaturus, Z. diahotensis nov. sp., close to Z. trilobus from the Australian Pleistocene. That kinship suggests a Plio-Pleistocene land connection between Australia and New Caledonia, whereas till now New Caledonia was supposed to be separated from Australia since the end of the Cretaceous, because of the total absence of indigenous mammals, fossil or recent, in New Caledonia. The latest geological studies in the East Pacific do not contradict our hypothesis.     

Contrasting levels of nucleotide diversity on the avian Z and W sex chromosomes

Sex chromosomes may provide a context for studying the local effects of mutation rate on molecular evolution, since the two types of sex chromosomes are generally exposed to different mutational environments in male and female germ lines. Importantly, recent studies of some vertebrates have provided evidence for a higher mutation rate among males than among females. Thus, in birds, the Z chromosome, which spends two thirds of its time in the male germ line, is exposed to more mutations than the female-specific W chromosome. We show here that levels of nucleotide diversity are drastically higher on the avian Z chromosome than in paralogous sequences on the W chromosome. In fact, no intraspecific polymorphism whatsoever was seen in about 3.4 kb of CHD1W intron sequence from a total of >150 W chromosome copies of seven different bird species. In contrast, the amount of genetic variability in paralogous sequences on the Z chromosome was significant, with an average pairwise nucleotide diversity (d) of 0.0020 between CHD1Z introns and with 37 segregating sites in a total of 3.8 kb of Z sequence. The contrasting levels of genetic variability on the avian sex chromosomes are thus in a direction predicted from a male-biased mutation rate. However, although a low gene number, as well as some other factors, argues against background selection and/or selective sweeps shaping the genetic variability of the avian W chromosome, we cannot completely exclude selection as a contributor to the low levels of variation on the W chromosome.     

Pairing of ZW gonosomes and the localized recombination nodule in two Z-autosome translocations in Gallus domesticus

Electron microscopic observations of synaptonemal complexes of oocytes from chickens heterozygous for two Z-autosome translocations have been used to identify and study the pairing region of the Z and W chromosomes. The two translocations, MN t(Z;1) and t(OH 10), have breakpoints in opposite arms of the Z, and the arm having the breakpoint of MN t(Z;1) is marked by the terminal C+ band. In both translocations the short arm of the W was specifically paired with the euchromatic short arm of the Z. In MN t(Z;1) only open quadrivalents (74%) and trivalents plus W univalents (26%) were observed, whereas t(OH 10) exhibited, in addition to the prevalent quadrivalents (62%), III + I (19%) and II + II (19%) configurations. The extent of W pairing was slightly decreased in MN t(Z;1) (68.4% of the W chromosomes paired) and considerably decreased in t(OH 10) (25.3% of the W chromosomes paired). Nonhomologous synapsis occurred regularly at the quadrivalent crosspoint in MN t(Z;1) and also in bivalents from t(OH 10). The recombination nodule normally located in the terminus of the pairing region in normal ZW pairs is present in both translocations without any alteration of its frequency or its strict terminal position. Based on these data and previous observations (Rahn and Solari, 1986), it is proposed that an obligatory recombination event occurs at a locus between 0.7 microns and 0.15 microns of the paired ZW telomeres, establishing a recombinational region and a pseudoautosomal region which determine partial sex-linkage and no sex-linkage, respectively. Most of the pairing region of the ZW pair is nonhomologously paired.     

Occurrence of multiple sexual chromosomes (XX/XY1Y2 and Z1Z1Z2Z2/Z1Z2W1W2) in catfishes of the genus Ancistrus (Siluriformes: Loricariidae) from the Amazon basin

Loricariid catfishes show a predominance of homomorphism in sex chromosomes, but cases of simple and multiple systems were also found. Here we describe two cases of multiple sex chromosome systems in loricariids from Brazilian Amazonia. Males of Ancistrus sp.1 "Balbina" have a modal number of 2n = 39 chromosomes, fundamental number (FN) of 78, and karyotypic formula of 27 m + 10 sm + 2 st; females have 2n = 38 chromosomes, FN = 76, and 26 m + 10 sm + 2 st. Ancistrus sp.2 "Barcelos" has 2n = 52 chromosomes for both sexes, FN = 80 for males and FN = 79 for females. Karyotypic formula is 12 m + 12 sm + 4 st + 24a for males and 11 m + 12 sm + 4st + 25a for females. The two species show different arrangements of constitutive heterochromatin blocks, which are coincident with NORs and absent in sex chromosomes. We suggest a XX/XY(1)Y(2) mechanism for Ancistrus sp.1 "Balbina", and a Z(1)Z(1)Z(2)Z(2)/Z(1)Z(2)W(1)W(2) mechanism for Ancistrus sp.2 "Barcelos". The XX/XY(1)Y(2) mechanism here reported is the second known occurrence of this type of multiple sex chromosomes for Loricariidae and the third for Neotropical fishes; the mechanism Z(1)Z(1)Z(2)Z(2)/Z(1)Z(2)W(1)W(2) represents the first record among fishes. The presence of different sex chromosome systems in Ancistrus indicates a probable independent origin and suggests that the differentiation of sex chromosomes is evolutionarily recent among species in this genus.     

Evolutionary and biogeographical implications of the karyological variations in the oviparous and viviparous forms of the lizard Lacerta (Zootoca) vivipara

The lizard Lacerta ( Zootoca ) vivipara has two modes of reproduction and is variable karyologically. We describe its karyological variation from literature data and from new data on two viviparous populations from France, on two oviparous populations from the Pyrenees in south-western France and on three oviparous populations recently discovered in Slovenia. Males have 36 chromosomes, whereas females have only 35 chromosomes in all viviparous populations and in the Pyrenean oviparous populations. This karyotype has been interpreted to result from a fusion of an ancestral sexual W chromosome with an autosome from the Zl or from the Z2 pair. The karyotype formula is 32 autosomes + ZIZ2W for the female and 32 autosomes + Z1Z1Z2Z2 for the male. The karyotype of the Slovenian oviparous populations, 34 autosomes + ZW in the male and 34 autosomes +ZW in the female, represents an evolutionary stage that preceded the chromosomal fusion. There is minor karyological variation, mainly concerning the W and Z2 chromosomes, within the Pyrenean oviparous populations. This parallels the geographic variation of the W-linked alleles of the MPI enzyme and suggests that allopatric differentiation of these oviparous populations might have occurred in the vicinity of the Pyrenees during the Pleistocene.
The viviparous populations from western Europe carry a metacentric W chromosome, whereas oviparous populations from south-western Europe and eastern viviparous populations both show an acrocentrie, or a subtelocentrie. W chromosome. This suggests that the acrocentric-subtelocentric W is a primitive character and that viviparity probably arose in an eastern lineage of the species.     

Multiple and independent cessation of recombination between avian sex chromosomes

Birds are characterized by female heterogamety; females carry the Z and W sex chromosomes, while males have two copies of the Z chromosome. We suggest here that full differentiation of the Z and W sex chromosomes of birds did not take place until after the split of major contemporary lineages, in the late Cretaceous. The ATP synthase alpha-subunit gene is now present in one copy each on the nonrecombining part of the W chromosome (ATP5A1W) and on the Z chromosome (ATP5A1Z). This gene seems to have evolved on several independent occasions, in different lineages, from a state of free recombination into two sex-specific and nonrecombining variants. ATP5A1W and ATP5A1Z are thus more similar within orders, relative to what W (or Z) are between orders. Moreover, this cessation of recombination apparently took place at different times in different lineages (estimated at 13, 40, and 65 million years ago in Ciconiiformes, Galliformes, and Anseriformes, respectively). We argue that these observations are the result of recent and traceable steps in the process where sex chromosomes gradually cease to recombine and become differentiated. Our data demonstrate that this process, once initiated, may occur independently in parallel in sister lineages.     

Alpha-1-antitrypsin: Evidence for a fifth PI M subtype and a new deficiency allele PI*ZAugsburg

Summary The phenotypes of the protease inhibitor (PI) alpha-1-antitrypsin have been analyzed by isoelectric focusing on polyacrylamide gels. With improved resolution by a modified procedure it was possible to demonstrate a fifth PI^*M suballele. The bands of PI M5 are located between PI M1 and PI M3. In addition, a further deficiency allele similar to PI^*Z was found in a female patient with obstructive pulmonary disease. This variant was provisionally named PI Zaugsburg (PI Zaug). Family data confirm a simple codominant mode of inheritance for PI Zaug.Dr. W. Jahn has met with a fatal accident on June 20th, 1985 while this paper was in press. This paper is dedicated to his memory