Algorithms to automatically quantify the geometric similarity of anatomical surfaces

We describe new approaches for distances between pairs of 2-dimensional surfaces (embedded in 3-dimensional space) that use local structures and global information contained in inter-structure geometric relationships. We present algorithms to automatically determine these distances as well as geometric correspondences. This is motivated by the aspiration of students of natural science to understand the continuity of form that unites the diversity of life. At present, scientists using physical traits to study evolutionary relationships among living and extinct animals analyze data extracted from carefully defined anatomical correspondence points (landmarks). Identifying and recording these landmarks is time consuming and can be done accurately only by trained morphologists. This renders these studies inaccessible to non-morphologists, and causes phenomics to lag behind genomics in elucidating evolutionary patterns. Unlike other algorithms presented for morphological correspondences our approach does not require any preliminary marking of special features or landmarks by the user. It also differs from other seminal work in computational geometry in that our algorithms are polynomial in nature and thus faster, making pairwise comparisons feasible for significantly larger numbers of digitized surfaces. We illustrate our approach using three datasets representing teeth and different bones of primates and humans, and show that it leads to highly accurate results.Comment: Changes with respect to v1, v2: an Erratum was added, correcting the references for one of the three datasets. Note that the datasets and code for this paper can be obtained from the Data Conservancy (see Download column on v1, v2

The Origin And Loss Of Periodic Patterning In The Turtle Shell

The origin of the turtle shell over 200 million years ago greatly modified the amniote body plan, and the morphological plasticity of the shell has promoted the adaptive radiation of turtles. The shell, comprising a dorsal carapace and a ventral plastron, is a layered structure formed by basal endochondral axial skeletal elements (ribs, vertebrae) and plates of bone, which are overlain by keratinous ectodermal scutes. Studies of turtle development have mostly focused on the bones of the shell; however, the genetic regulation of the epidermal scutes has not been investigated. Here, we show that scutes develop from an array of patterned placodes and that these placodes are absent from a soft-shelled turtle in which scutes were lost secondarily. Experimentally inhibiting Shh, Bmp or Fgf signaling results in the disruption of the placodal pattern. Finally, a computational model is used to show how two coupled reaction-diffusion systems reproduce both natural and abnormal variation in turtle scutes. Taken together, these placodal signaling centers are likely to represent developmental modules that are responsible for the evolution of scutes in turtles, and the regulation of these centers has allowed for the diversification of the turtle shell

Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption we performed a population based genome-wide association study of ‘age at first tooth’ and ‘number of teeth’ using 5998 and 6609 individuals respectively from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2,446,724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of fifteen independent loci, with ten loci reaching genome-wide significance (p<5x10−8) for ‘age at first tooth’ and eleven loci for ‘number of teeth’. Together these associations explain 6.06% of the variation in ‘age of first tooth’ and 4.76% of the variation in ‘number of teeth’. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including a SNP in the protein-coding region of BMP4 (rs17563, P= 9.080x10−17). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development

Prenatal ultrasound and postmortem histologic evaluation of tooth germs: an observational, transversal study

Introduction: Hypodontia is the most frequent developmental anomaly of the orofacial complex, and its detection in prenatal ultrasound may indicate the presence of congenital malformations, genetic syndromes and chromosomal abnormalities.To date, only a few studies have evaluated the histological relationship of human tooth germs identified by two-dimensional (2D) ultrasonography. In order to analyze whether two-dimensional ultrasonography of tooth germs may be successfully used for identifying genetic syndromes, prenatal ultrasound images of fetal tooth germs obtained from a Portuguese population sample were compared with histological images obtained from fetal autopsies.Methods: Observational, descriptive, transversal study. The study protocol followed the ethical principles outlined by the Helsinki Declaration and was approved by the Ethics Committee of the School of Dental Medicine, University of Porto (FMDUP, Porto, Portugal) and of the Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/EPE, Porto, Portugal) as well as by the CGC Genetics Embryofetal Pathology Laboratory. Eighty-five fetuses examined by prenatal ultrasound screening from May 2011 to August 2012 had an indication for autopsy following spontaneous fetal death or medical termination of pregnancy. Of the 85 fetuses, 37 (43.5%) were randomly selected for tooth germ evaluation by routine histopathological analysis. Fetuses who were up to 30 weeks of gestation, and whose histological pieces were not representative of all maxillary tooth germs was excluded. Twenty four fetus between the 13th and 30th weeks of gestation fulfilled the parameters to autopsy.Results: Twenty four fetuses were submitted to histological evaluation and were determined the exact number, morphology, and mineralization of their tooth germs. All tooth germs were identifiable with ultrasonography as early as the 13th week of gestation. Of the fetuses autopsied, 41.7% had hypodontia (29.1% maxillary hypodontia and 20.9% mandibular hypodontia).Conclusions: This results indicateinfo:eu-repo/semantics/publishedVersio

Modeling enamel matrix secretion in mammalian teeth

The most mineralized tissue of the mammalian body is tooth enamel. Especially in species with thick enamel, three-dimensional (3D) tomography data has shown that the distribution of enamel varies across the occlusal surface of the tooth crown. Differences in enamel thickness among species and within the tooth crown have been used to examine taxonomic affiliations, life history, and functional properties of teeth. Before becoming fully mineralized, enamel matrix is secreted on the top of a dentine template, and it remains to be explored how matrix thickness is spatially regulated. To provide a predictive framework to examine enamel distribution, we introduce a computational model of enamel matrix secretion that maps the dentine topography to the enamel surface topography. Starting from empirical enamel-dentine junctions, enamel matrix deposition is modeled as a diffusion-limited free boundary problem. Using laboratory microCT and synchrotron tomographic data of pig molars that have markedly different dentine and enamel surface topographies, we show how diffusion-limited matrix deposition accounts for both the process of matrix secretion and the final enamel distribution. Simulations reveal how concave and convex dentine features have distinct effects on enamel surface, thereby explaining why the enamel surface is not a straightforward extrapolation of the dentine template. Human and orangutan molar simulations show that even subtle variation in dentine topography can be mapped to the enamel surface features. Mechanistic models of extracellular matrix deposition can be used to predict occlusal morphologies of teeth. Author summary Teeth of most mammals are covered by a layer of highly mineralized enamel that cannot be replaced or repaired. The enamel layer is not uniform over the underlying dentine, and spatial regulation of enamel formation is critical for making a functional tooth. To explore which kind of mechanisms could underlie the complex patterns of enamel distribution, we present a computational model. Starting from tomography-imaged teeth from which enamel has been digitally removed, enamel is restored on dentine surfaces by simulating diffusion-limited secretion of enamel matrix. Our simulations show how the combination of subtle features of dentine and diffusion-limited secretion of the enamel matrix can substantially increase the complexity of the enamel surface. We propose that the strength of the diffusion-limited process is a key factor in determining enamel distribution among mammalian species.Peer reviewe

The effect of amoxicillin on dental enamel development in vivo

The exposure to amoxicillin has been associated with molar incisor hypomineralization. This study aimed to determine if amoxicillin disturbs the enamel mineralization in in vivo experiments. Fifteen pregnant rats were randomly assigned into three groups to received daily phosphatase-buffered saline or amoxicillin as either 100 or 500 mg/kg. Mice received treatment from day 13 of pregnancy to day 40 postnatal. After birth, the offsprings from each litter continued to receive the same treatment according to their respective group. Calcium (Ca) and phosphorus (P) content in the dental hard tissues were analyzed from 60 upper first molars and 60 upper incisors by the complexometric titration method and colorimetric analysis using a spectrophotometer at 680 nm, respectively. Lower incisors were analyzed by X-ray microtomography, it was measured the electron density of lingual and buccal enamel, and the enamel and dentin thickness. Differences in Ca and P content and electron density among the groups were analyzed by one-way ANOVA. There was no significant difference on enamel electron density and thickness among the groups (p > 0.05). However, in incisors, the higher dose of amoxicillin decreased markedly the electron density in some rats. There were no statistically significant differences in Ca (p = 0.180) or P content (p = 0.054), although the higher dose of amoxicillin could affect the enamel in some animals. The amoxicillin did not significantly alter the enamel mineralization and thickness in rats. © 2020Peer reviewe

Early Holocene fauna from a new subfossil site: A first assessment from Christmas River, south central Madagascar

We report on faunal remains recovered during recent explorations at &#8216;Christmas River&#8217;, the only subfossil locality known from Madagascar&#8217;s south central plateau. Recovered remains of several extinct taxa date to approximately 10,000 14C years before present (BP), including crocodiles, tortoises, the elephant bird Aepyornis, the carnivoran Cryptoprocta spelea, the lemurs Archaeolemur majori, Pachylemur insignis, and Megaladapis edwardsi, and abundant remains of the dwarf hippopotamus, Hippopotamus lemerlei. The presence of southern - limited, forest - dependent species at Christmas River supports the hypothesis that forest once extended, perhaps discontinuously, across the central highlands towards the west. One theory is that sites in the north central highlands, which are higher in elevation, maintained more mesic conditions during Plio - Quaternary climate shifts than those of the lower elevation sites of the south central highlands. Thus, elevation above sea level may have acted as a filter that limited species dispersal across the island in the past. Such a scenario would explain the distinction between more humid, higher elevation, northern highland subfossil communities versus more arid, lower elevation, southern subfossil communities. Continued exploration at Christmas River thus provides a remarkable opportunity for deciphering ecological changes that have taken place in south central Madagascar during the Holocene.R&#201;SUM&#201;Madagascar est reconnue comme l&#8217;une des r&#233;gions les plus sensibles du monde en ce qui concerne les menaces pesant sur sa biodiversit&#233;, et cela &#224; cause de niveaux d&#8217;end&#233;misme in&#233;gal&#233;s, d&#8217;une diversit&#233; vari&#233;e et d&#8217;un impact humain important sur l&#8217;environnement. Suite &#224; la colonisation par l&#8217;Homme il y a plus de 2000 ans, des extinctions de masse de la faune et un important recul forestier ont eu lieu en laissant des marques sur les &#233;cosyst&#232;mes modernes qui sont dans un &#233;tat de bouleversement &#233;cologique. Certaines plantes end&#233;miques, par exemple, ont perdu d&#8217;importantes esp&#232;ces mutualistes, des animaux ont &#233;t&#233; oblig&#233;s d&#8217;exploiter d&#8217;autres ressources ou habiter des endroits auxquels ils sont mal adapt&#233;s. La diversit&#233; des plantes et des animaux a diminu&#233;, est menac&#233;e ou a m&#234;me compl&#232;tement disparue de certaines routes de diss&#233;mination. Bien que l&#8217;Homme soit largement incrimin&#233; dans son r&#244;le de d&#233;clencheur de ces extinctions massives, les transformations anthropiques qui ont contribu&#233; au changement du climat sont controvers&#233;es. Les hautes - terres de Madagascar sont actuellement domin&#233;es par des zones herbeuses &#233;tendues qui agissent comme des barri&#232;res emp&#234;chant les mouvements de la faune de part et d&#8217;autre de l&#8217;&#238;le. Nous sugg&#233;rons qu&#8217;une for&#234;t humide plus ou moins continue devait s&#8217;&#233;tendre sur les hautes-terres. Des informations pal&#233;o&#233;cologiques des hautes - terres du Centre sud sont&#232;n&#233;cessaires pour &#233;valuer cette hypoth&#232;se afin de d&#233;m&#234;ler la contribution relative des facteurs climatiques et anthropiques dans les changements pal&#233;o&#233;cologiques de la r&#233;gion. Cependant, les stations de subfossiles &#233;taient jusqu&#8217;alors inconnues dans cette r&#233;gion. Nous pr&#233;sentons ici les r&#233;sultats de recherches r&#233;alis&#233;es sur les restes fauniques d&#233;couverts au cours de fouilles r&#233;centes &#224; Christmas River, la seule station de subfossiles connue des hautes - terres du Centre sud de Madagascar. Des restes de plusieurs esp&#232;ces datant approximativement de 10,000 14C B.P. ont &#233;t&#233; identifi&#233;s dont des restes appartenant &#224; des esp&#232;ces de crocodile, de tortue, de l&#8217;Aepyornis, du carnivore Cryptoprocta spelea, des l&#233;muriens Archaeolemur majori, Pachylemur insignis et Megaladapis edwardsi ainsi que de nombreux restes de l&#8217;hippopotame nain Hippopotamus lemerlei. La pr&#233;sence &#224; Christmas River d&#8217;esp&#232;ces sylvicoles end&#233;miques du Sud appuie l&#8217;hypoth&#232;se de l&#8217;existence d&#8217;une for&#234;t, certainement discontinue, mais qui s&#8217;&#233;tendait sur les hautes - terres centrales en se poursuivant vers l&#8217;ouest. Une th&#233;orie a propos&#233; que les sites septentrionaux des hautes - terres centrales, &#224; des altitudes plus &#233;lev&#233;es, maintenaient des conditions plus humides au cours des changements du Plio - quaternaire que les sites m&#233;ridionaux de ces hautes - terres centrales. Ainsi, dans le pass&#233;, l&#8217;altitude a du agir comme un filtre qui emp&#234;chait la dispersion des esp&#232;ces d&#8217;un endroit &#224; l&#8217;autre de l&#8217;&#238;le. Un tel sc&#233;nario expliquerait la distinction entre les communaut&#233;s subfossiles du nord des hautes - terres qui &#233;taient plus humides &#224; haute altitude et les communaut&#233;s subfossiles du sud aride &#224; basse altitude. La poursuite de l&#8217;exploration &#224; Christmas River constitue une occasion unique pour d&#233;coder les changements &#233;cologiques qui sont intervenus dans le Sud de cette r&#233;gion centrale de Madagascar au cours de l&#8217;Holoc&#232;ne

Development and regeneration of the crushing dentition of skates (Rajidae)

Sharks and rays (elasmobranchs) have the remarkable capacity to continuously regenerate their teeth. The polyphyodont system is considered the ancestral condition of the gnathostome dentition. Despite this shared regenerative ability, sharks and rays exhibit dramatic interspecific variation in their tooth morphology. Ray (batoidea) teeth typically constitute crushing pads of flattened teeth, whereas shark teeth are pointed, multi-cuspid units. Although recent research has addressed the molecular development of the shark dentition, little is known about that of the ray. Furthermore, how dental diversity within the elasmobranch lineage is achieved remains unknown. Here, we examine dental development and regeneration in two Batoid species: the thornback skate (Raja clavata) and the little skate (Leucoraja erinacea). Using in situ hybridization and immunohistochemistry, we examine the expression of a core gnathostome dental gene set during early development of the skate dentition and compare it to development in the shark. Elasmobranch tooth development is highly conserved, with sox2 likely playing an important role in the initiation and regeneration of teeth. Alterations to conserved genes expressed in an enamel knot-like signalling centre may explain the morphological diversity of elasmobranch teeth, thereby enabling sharks and rays to occupy diverse dietary and ecological niches

Quantitative Genetics, Pleiotropy, and Morphological Integration in the Dentition of Papio hamadryas

Variation in the mammalian dentition is highly informative of adaptations and evolutionary relationships, and consequently has been the focus of considerable research. Much of the current research exploring the genetic underpinnings of dental variation can trace its roots to Olson and Miller's 1958 book Morphological Integration. These authors explored patterns of correlation in the post-canine dentitions of the owl monkey and Hyopsodus, an extinct condylarth from the Eocene. Their results were difficult to interpret, as was even noted by the authors, due to a lack of genetic information through which to view the patterns of correlation. Following in the spirit of Olson and Miller's research, we present a quantitative genetic analysis of dental variation in a pedigreed population of baboons. We identify patterns of genetic correlations that provide insight to the genetic architecture of the baboon dentition. This genetic architecture indicates the presence of at least three modules: an incisor module that is genetically independent of the post-canine dentition, and a premolar module that demonstrates incomplete pleiotropy with the molar module. We then compare this matrix of genetic correlations to matrices of phenotypic correlations between the same measurements made on museum specimens of another baboon subspecies and the Southeast Asian colobine Presbytis. We observe moderate significant correlations between the matrices from these three primate taxa. From these observations we infer similarity in modularity and hypothesize a common pattern of genetic integration across the dental arcade in the Cercopithecoidea

Loss of heterozygosity at 18q21 is indicative of recurrence and therefore poor prognosis in a subset of colorectal cancers

Adjuvant therapies are increasingly used in colorectal cancers for the prevention of recurrence. These therapies have side-effects and should, thus, be used only if really beneficial. However, the development of recurrence cannot be predicted reliably at the moment of diagnosis, and targeting of adjuvant therapies is thus based only on the primary stage of the cancer. Loss of heterozygosity (LOH) in the long arm of chromosome 18 is suggested to be related to poor survival and possibly to the development of metastases. We studied the value of LOH at 18q21 as a marker of colorectal cancer prognosis, association with clinicopathological variables, tumour recurrence and survival of the patients. Of the 255 patients studied, 195 were informative as regards LOH status when analysed in primary colorectal cancer specimens using the polymerase chain reaction (PCR) and fragment analysis. LOH at 18q21 was significantly associated with the development of recurrence (P= 0.01) and indicated poor survival in patients of Dukes' classes B and C, in which most recurrences (82%) occurred. An increased rate of tumour recurrence is the reason for poor survival among patients with LOH at 18q21 in primary cancer. These patients are a possible target group for recurrence-preventing adjuvant therapies. © 1999 Cancer Research Campaig