Faculty Bibliography

OBJECTIVES: While dental development is important to life history investigations, data from wild known-aged great apes are scarce. We report on the first radiographic examination of dental development in wild Virunga mountain gorillas, using known-age skeletal samples recovered in Rwanda. MATERIALS AND METHODS: In 43 individuals (0.0-14.94 years), we collected radiographs of mandibular molars, and where possible, cone beam CT scans. Molar crown and root calcification status was assessed using two established staging systems, and age prediction equations generated using polynomial regression. Results were compared to available data from known-age captive and wild chimpanzees. RESULTS: Mountain gorillas generally fell within reported captive chimpanzee distributions or exceeded them, exhibiting older ages at equivalent radiographic stages of development. Differences reflect delayed initiation and/or an extended duration of second molar crown development, and extended first and second molar root development, in mountain gorillas compared to captive chimpanzees. However, differences in the duration of molar root development were less evident compared to wild chimpanzees. DISCUSSION: Despite sample limitations, our findings extend the known range of variation in radiographic estimates of molar formation timing in great apes, and provide a new age prediction technique based on wild specimens. However, mountain gorillas do not appear accelerated in radiographic assessment of molar formation compared to chimpanzees, as they are for other life history traits. Future studies should aim to resolve the influence of species differences, wild versus captive environments, and/or sampling phenomena on patterns observed here, and more generally, how they relate to variation in tooth size, eruption timing, and developmental life history.

Loss-of-function mutations in stromal interaction molecule 1 (STIM1) impair the activation of Ca2+ release-activated Ca2+ (CRAC) channels and store-operated Ca2+ entry (SOCE), resulting in a disease syndrome called CRAC channelopathy that is characterized by severe dental enamel defects. The cause of these enamel defects has remained unclear given a lack of animal models. We generated Stim1/2K14cre mice to delete STIM1 and its homolog STIM2 in enamel cells. These mice showed impaired SOCE in enamel cells. Enamel in Stim1/2K14cre mice was hypomineralized with decreased Ca content, mechanically weak, and thinner. The morphology of SOCE-deficient ameloblasts was altered, showing loss of the typical ruffled border, resulting in mislocalized mitochondria. Global gene expression analysis of SOCE-deficient ameloblasts revealed strong dysregulation of several pathways. ER stress genes associated with the unfolded protein response were increased in Stim1/2-deficient cells, whereas the expression of components of the glutathione system were decreased. Consistent with increased oxidative stress, we found increased ROS production, decreased mitochondrial function, and abnormal mitochondrial morphology in ameloblasts of Stim1/2K14cre mice. Collectively, these data show that loss of SOCE in enamel cells has substantial detrimental effects on gene expression, cell function, and the mineralization of dental enamel.

Studies of variation in orientation of collagen fibers within bone have lead to the proposition that these are preferentially aligned to accommodate different kinds of load, with tension best resisted by fibers aligned longitudinally relative to the load, and compression best resisted by transversely aligned fibers. However, previous studies have often neglected to consider the effect of developmental processes, including constraints on collagen fiber orientation (CFO), particularly in primary bone. Here we use circularly polarized light microscopy to examine patterns of CFO in cross-sections from the midshaft femur, humerus, tibia, radius and ulna in a range of living primate taxa with varied body sizes, phylogenetic relationships and positional behaviors. We find that a preponderance of longitudinally oriented collagen is characteristic of both periosteal primary and intracortically remodeled bone. Where variation does occur among groups, it is not simply understood via interpretations of mechanical loads, although prioritized adaptations to tension and/or shear are considered. While there is some suggestion that CFO may correlate with body size, this relationship is neither consistent nor easily explicable through consideration of size-related changes in mechanical adaptation. The results of our study indicate that there is no clear relationship between CFO and phylogenetic status. One of the principle factors accounting for the range of variation that does exist is primary tissue type, where slower depositing bone is more likely to comprise a larger proportion of oblique to transverse collagen fibers

Osteocytes can remove and remodel small amounts of their surrounding bone matrix through osteocytic osteolysis, which results in increased volume occupied by lacunar and canalicular space (LCS). It is well established that cortical bone stiffness and strength are strongly and inversely correlated with vascular porosity, but whether changes in LCS volume caused by osteocytic osteolysis are large enough to affect bone mechanical properties is not known. In the current studies we tested the hypotheses that i) lactation and post-lactation recovery in mice alter the elastic modulus of bone tissue, and ii) such local changes in mechanical properties are related predominantly to alterations in lacunar and canalicular volume rather than bone matrix composition. Mechanical testing was performed using microindentation to measure modulus in regions containing solely osteocytes and no vascular porosity. Lactation caused a significant ( approximately 13%) reduction in bone tissue-level elastic modulus (p < 0.001). After 1 week post-weaning (recovery), bone modulus levels returned to control levels and did not change further after four weeks of recovery. LCS porosity tracked inversely with changes in cortical bone modulus. Lacunar and canalicular void space increased 7% and 15% with lactation, respectively (p < 0.05), then returned to control levels at 1 week after weaning. Neither bone mineralization (assessed by high resolution Backscattered Scanning Electron Microscopy) nor mineral/matrix ratio or crystallinity (assessed by Raman microspectroscopy) changed with lactation. Thus, changes in bone mechanical properties induced by lactation and recovery appear to depend predominantly on changes in osteocyte LCS dimensions. Moreover, this study demonstrates that tissue-level cortical bone mechanical properties are rapidly and reversibly modulated by osteocytes in response to physiological challenge. These data point to a hitherto unappreciated role for osteocytes in modulating and maintaining local bone mechanical properties

We show that statistical modeling of analytical results is useful in providing insights into metabolism and disease in bioarcheology. Our results also imply that during the Renaissance in Europe widespread pollution of the biosphere with heavy metals such as mercury and lead affected the Italian nobility at that time.The activity of biologic clocks which control metabolism and autonomic nervous system (ANS) function can be gleaned from the analysis of hair. This provides a means of assessing the health of individuals who lived some six centuries before the present and allows the reconstruction of disease from archived tissues such as hair.

OBJECTIVES: It remains unclear how the realignments of the face and basicranium that characterize humans were acquired, both phylogenetically and ontogenetically. The developmentally constrained nature of the skull has been previously demonstrated in other primates using Donald H. Enlow's mammalian craniofacial architectural relationships. Here, we compare crania of our closest relatives to gain greater understanding of how and why the relationship of the face and cranial base is developmentally constrained in order to inform instances of abnormal growth and clinical intervention. STUDY DESIGN: A method for evaluating these fundamental architectural relationships using 3D landmark data was developed, thereby taking overall size and the geometric relationships among points into account. A sample of cone-beam computed tomography scans derived from humans and extant apes were analyzed (n=10 and n=6, respectively), as well as fossil hominid crania (n=7). Landmarks for 23 craniofacial architectural points were identified and recorded. RESULTS AND CONCLUSIONS: Principal components analyses reveal that despite the similarities in craniofacial architecture between humans, extant apes and fossil hominids, appreciable trends in variation between the extant species suggest that the repositioning of the foramen magnum was only one of a constellation of traits that realigned the basicranium and face during the transition to bipedalism.

Large-scale patterns evident from satellite images of aeolian landforms on Earth and other planets; those of intermediate scale in marine and terrestrial sand ripples and sediment profiles; and small-scale patterns such as lamellae in the bones of vertebrates and annuli in fish scales are each represented by layers of different thicknesses and lengths. Layered patterns are important because they form a record of the state of internal and external factors that regulate pattern formation in these geological and biological systems. It is therefore potentially possible to recognize trends, periodicities, and events in the history of the formation of these systems among the incremental sequences. Though the structures and sizes of these 2-D patterns are typically scale-free, they are also characteristically anisotropic; that is, the number of layers and their absolute thicknesses vary significantly during formation. The aim of the present work is to quantify the structure of layered patterns and to reveal similarities and differences in the processing and interpretation of layered landforms and biological systems. To reach this goal we used N-partite graph and Boolean functions to quantify the structure of layers and plot charts for "layer thickness vs. layer number" and "layer area vs. layer number". These charts serve as a source of information about events in the history of formation of layered systems. The concept of synchronization of layer formation across a 2-D plane is introduced to develop the procedure for plotting "layer thickness vs. layer number" and "layer area vs. layer number", which takes into account the structural anisotropy of layered patterns and increase signal-to-noise ratio in charts. Examples include landforms on Mars and Earth and incremental layers in human and iguana bones.

Our objective in this study is to assess variation in Havers-Halberg oscillation (HHO) periodicities among domestic dogs (Canis familiaris). The HHO is hypothesized to be a biological rhythm controlled by the hypothalamus, acting as a central coordinator of multiple life history variables including body size, metabolic rate, and reproductive output. The periodicity of this clock varies among and within species, but not within individuals. It has been studied in detail among primates, though very little among other mammals. In monkeys and apes, the periodicity is strongly correlated with body mass, but lemurs show a restricted range of variation in HHO rhythm despite having a comparable range of body sizes. This raises the question of how HHO rhythms and body size evolution can be decoupled. Domestic dogs represent a potential means to shed light on this area, due to their wide range of body sizes accompanied by low variation in life history variables such as lifespan. Based on this, we hypothesize that dogs will resemble lemurs in HHO variation. To test this, we sectioned teeth of 11 previously deceased Canis familiaris from a university collection, representing a variety of breeds. Teeth preserve a histological marker of the HHO rhythm in the form of growth increments known as striae of Retzius, and the HHO rhythm can be quantified by counting the number of 24-hour growth lines between them. Teeth were cleaned, embedded in acrylic resin, thin sectioned, and mounted to microscope slides following standard dental histology protocols. They were then imaged using circularly polarized light microscopy so that their growth increments could be measured to assess HHO periodicity. Next, HHO periodicity was regressed against body mass estimate data acquired via estimation from mandibular length measurements. As predicted, domestic dogs have a low range of HHO periodicity variation for their body size range, falling between 4 and 6 days (with a modal value of 5). This suggests that dog body size variation is attributed to mechanisms beyond the HHO; conversely, the narrow range of variation in HHO can potentially explain the lack of variation in life history factors such as lifespan among dogs. Since body mass variation among domestic dogs is postulated to result from a mutation in IGF-1, this provides a possible explanation for the high body mass / low HHO variation seen in lemurs as well

The aim of our research is to document osteocyte lacuna density (OCD) and its biological significance among humans of known life history. Twelve human midshaft femurs obtained from sub-Saharan Africans (Malawi) of Bantu origin and known life history were prepared for backscattered electron microscopy in the scanning electron microscope (BSE-SEM). Lacunae have a characteristic size and aspect ratio in BSE-SEM images that allowed them to be identified and automatically enumerated relative to the detected bone area in all of the images processed; values for adult whole femoral midshaft cross sections averaged about 100,000 osteocyte lacunae. Statistical tests reveal significant relationships between both OCD and osteocyte lacuna area with body height. It appears that the same increase in energetic efficiency observed in interspecific comparisons of the mass specific metabolic rate of bone at larger body sizes also characterizes body size categories among humans. Long period biological rhythms that regulate rates of cell proliferation explain some aspects of human body size variability. (C) 2015 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.