Prolonged cyclical loading induces Haversian remodeling in mandibles of growing rabbits.

Bone adaptation to mechanical loading happens predominantly via modeling and remodeling, but the latter is poorly understood. Haversian remodeling (cortical bone replacement resulting in secondary osteons) is thought to occur in regions of low strain as part of bone maintenance or high strain in response to microdamage. However, analyses of remodeling in primates have revealed an unappreciated association with the number of daily load cycles. We tested this relationship by raising 30 male domestic rabbits (Oryctolagus cuniculus) on disparate diets from weaning to adulthood (48 weeks), facilitating a naturalistic perspective on mandibular bone adaptation. A control group consumed only rabbit pellets and an 'overuse' group ate hay in addition to pellets. To process hay, which is tougher and stiffer, rabbits increase chewing investment and duration without increasing bite force (i.e. corpus mean peak strain is similar for the two foods). Corpus remodeling in overuse rabbits was ∼1.5 times that of controls, measured as osteon population density and percentage Haversian bone. In the same subjects, there was a significant increase in overuse corpus bone formation (ratio of cortical area to cranial length), consistent with previous reports on the same dietary manipulation and bone formation in rabbits. This is the first evidence that both modeling and remodeling are simultaneously driven by the number of load cycles, independent of strain magnitude. This novel finding provides unique data on the feeding apparatus, challenges traditional thought on Haversian remodeling, and highlights the need for experimental studies of skeletal adaptation that examine mechanical factors beyond strain magnitude.

Internal architecture of the mandibular condyle of rabbits is related to dietary resistance during growth.

Although there is considerable evidence that bone responds to the loading environment in which it develops, few analyses have examined phenotypic plasticity or bone functional adaptation in the masticatory apparatus. Prior work suggests that masticatory morphology is sensitive to differences in food mechanical properties during development; however, the importance of the timing/duration of loading and variation in naturalistic diets is less clear. Here, we examined microstructural and macrostructural differences in the mandibular condyle in four groups of white rabbits (Oryctolagus cuniculus) raised for a year on diets that varied in mechanical properties and timing of the introduction of mechanically challenging foods, simulating seasonal variation in diet. We employed sliding semilandmarks to locate multiple volumes of interest deep to the mandibular condyle articular surface, and compared bone volume fraction, trabecular thickness and spacing, and condylar size/shape among experimental groups. The results reveal a shared pattern of bony architecture across the articular surface of all treatment groups, while also demonstrating significant among-group differences. Rabbits raised on mechanically challenging diets have significantly increased bone volume fraction relative to controls fed a less challenging diet. The post-weaning timing of the introduction of mechanically challenging foods also influences architectural properties, suggesting that bone plasticity can extend well into adulthood and that bony responses to changes in loading may be rapid. These findings demonstrate that bony architecture of the mandibular condyle in rabbits responds to variation in mechanical loading during an organism's lifetime and has the potential to track dietary variation within and among species.

Teaching an old jaw new tricks: diet-induced plasticity in a model organism from weaning to adulthood.

Many organisms exhibit a decrease in the ability to modify their phenotypes in response to shifts in environmental conditions as they mature. Such age-dependent plasticity has important implications in a variety of evolutionary and ecological contexts, particularly with respect to understanding adaptive responses to heterogeneous environments. In this study, we used experimental diet manipulation to examine the life-history trajectory of plasticity in the feeding complex of a model organism, the white rabbit (Oryctolagus cuniculus). We demonstrate that, contrary to expectations derived from previous cross-sectional studies of skeletal plasticity, the jaws of weanlings and young adults exhibit similar increases in relative bone cross-sectional areas in response to the introduction of mechanically challenging foods into their diets. Furthermore, we present evidence that sensitivity to loading patterns persists well into adulthood in some regions of the masticatory apparatus in rabbits, indicating that there is an extended window of opportunity to respond to changes in dietary properties during an animal's life span. We conclude that certain aspects of the facial skeleton of rabbits, and perhaps mammals in general, are sensitive to environmental stimuli long after skeletal maturity is achieved, highlighting the importance of plasticity as a source of adaptive variation at later life-history stages.

Experimental perspective on fallback foods and dietary adaptations in early hominins.

The robust jaws and large, thick-enameled molars of the Plio-Pleistocene hominins Australopithecus and Paranthropus have long been interpreted as adaptations for hard-object feeding. Recent studies of dental microwear indicate that only Paranthropus robustus regularly ate hard items, suggesting that the dentognathic anatomy of other australopiths reflects rare, seasonal exploitation of hard fallback foods. Here, we show that hard-object feeding cannot explain the extreme morphology of Paranthropus boisei. Rather, analysis of long-term dietary plasticity in an animal model suggests year-round reliance on tough foods requiring prolonged postcanine processing in P. boisei. Increased consumption of such items may have marked the earlier transition from Ardipithecus to Australopithecus, with routine hard-object feeding in P. robustus representing a novel behaviour.

Functional and morphological correlates of mandibular symphyseal form in a living human sample.

Variation in recent human mandibular form is often thought to reflect differences in masticatory behavior associated with variation in food preparation and subsistence strategies. Nevertheless, while mandibular variation in some human comparisons appear to reflect differences in functional loading, other comparisons indicate that this relationship is not universal. This suggests that morphological variation in the mandible is influenced by other factors that may obscure the effects of loading on mandibular form. It is likely that highly strained mandibular regions, including the corpus, are influenced by well-established patterns of lower facial skeletal integration. As such, it is unclear to what degree mandibular form reflects localized stresses incurred during mastication vs. a larger set of correlated features that may influence bone distribution patterns. In this study, we examine the relationship between mandibular symphyseal bone distribution (i.e., second moments of area, cortical bone area) and masticatory force production (i.e., in vivo maximal bite force magnitude and estimated symphyseal bending forces) along with lower facial shape variation in a sample of n = 20 living human male subjects. Our results indicate that while some aspects of symphyseal form (e.g., wishboning resistance) are significantly correlated with estimates of symphyseal bending force magnitude, others (i.e., vertical bending resistance) are more closely tied to variation in lower facial shape. This suggests that while the symphysis reflects variation in some variables related to functional loading, the complex and multifactorial influences on symphyseal form underscores the importance of exercising caution when inferring function from the mandible especially in narrow taxonomic comparisons.

Viewpoints: feeding mechanics, diet, and dietary adaptations in early hominins.

Inference of feeding adaptation in extinct species is challenging, and reconstructions of the paleobiology of our ancestors have utilized an array of analytical approaches. Comparative anatomy and finite element analysis assist in bracketing the range of capabilities in taxa, while microwear and isotopic analyses give glimpses of individual behavior in the past. These myriad approaches have limitations, but each contributes incrementally toward the recognition of adaptation in the hominin fossil record. Microwear and stable isotope analysis together suggest that australopiths are not united by a single, increasingly specialized dietary adaptation. Their traditional (i.e., morphological) characterization as "nutcrackers" may only apply to a single taxon, Paranthropus robustus. These inferences can be rejected if interpretation of microwear and isotopic data can be shown to be misguided or altogether erroneous. Alternatively, if these sources of inference are valid, it merely indicates that there are phylogenetic and developmental constraints on morphology. Inherently, finite element analysis is limited in its ability to identify adaptation in paleobiological contexts. Its application to the hominin fossil record to date demonstrates only that under similar loading conditions, the form of the stress field in the australopith facial skeleton differs from that in living primates. This observation, by itself, does not reveal feeding adaptation. Ontogenetic studies indicate that functional and evolutionary adaptation need not be conceptually isolated phenomena. Such a perspective helps to inject consideration of mechanobiological principles of bone formation into paleontological inferences. Finite element analysis must employ such principles to become an effective research tool in this context.

Bone remodeling and cyclical loading in maxillae of New Zealand white rabbits (Oryctolagus cuniculus).

Mammalian feeding behaviors are altered when mechanically challenging (e.g., tough, stiff) foods require large bite forces or prolonged mastication. Bony responses to high bite forces are well-documented for the mammalian skull, but osteogenesis due to cyclical loading, caused by repetitive chewing, is more poorly understood. Previous studies demonstrate that cyclical loading results in greater bone formation in the rabbit masticatory apparatus and in substantial Haversian remodeling in primate postcrania. Here we assess the relationship between cyclical loading and remodeling in the rabbit maxilla. Twenty male New Zealand white rabbits (Oryctolagus cuniculus) were raised on either an overuse or control diet (10 per group) for 48 weeks, beginning at weaning onset. The control group was raised on a diet of rabbit pellets (E = 29 MPa, R = 1031 J/m2 ), whereas the overuse group ate rabbit pellets and hay, which has high stiffness (E = 3336 MPa) and toughness (R = 2760 J/m2 ) properties. Hay requires greater chewing investment (475 chews/g) and longer chewing durations (568 s/g) than pellets (161 chews/g and 173 s/g), therefore causing cyclical loading of the jaws. Remodeling was measured as osteon population density (OPD), percent Haversian bone (%HAV), and osteon cross-sectional area (On.Ar). The only significant difference found was greater On.Ar in the alveolar region of the maxilla (p < 0.001) in the overuse group. The hypothesis that cyclical loading engenders Haversian remodeling in the developing maxilla is not supported. The continuation of modeling throughout the experimental duration may negate the need for remodeling as newly laid bone tends to be more compliant and resistant to crack propagation.

Ontogeny and phyletic size change in living and fossil lemurs.

Lemurs are notable for encompassing the range of body-size variation for all primates past and present-close to four orders of magnitude. Benefiting from the phylogenetic proximity of subfossil lemurs to smaller-bodied living forms, we employ allometric data from the skull to probe the ontogenetic bases of size differentiation and morphological diversity across these clades. Building upon prior pairwise comparisons between sister taxa, we performed the first clade-wide analyses of craniomandibular growth allometries in 359 specimens from 10 lemuroids and 176 specimens from 8 indrioids. Ontogenetic trajectories for extant forms were used as a criterion of subtraction to evaluate morphological variation, and putative adaptations among sister taxa. In other words, do species-level differences in skull form result from the differential extension of common patterns of relative growth?In lemuroids, a pervasive pattern of ontogenetic scaling is observed for facial dimensions in all genera, with three genera also sharing relative growth trajectories for jaw proportions (Lemur, Eulemur, Varecia). Differences in masticatory growth and form characterizing Hapalemur and fossil Pachylemur likely reflect dietary factors. Pervasive ontogenetic scaling characterizes the facial skull in extant Indri, Avahi, and Propithecus, as well as their larger, extinct sister taxa Mesopropithecus and Babakotia. Significant interspecific differences are observed in the allometry of indrioid masticatory proportions, with variation in the mechanical advantage of the jaw adductors and stress-resisting elements correlated with diet. As the growth series and adult data are largely coincidental in each clade, interspecific variation in facial form may result from selection for body-size differentiation among sister taxa. Those cases where trajectories are discordant identify potential dietary adaptations linked to variation in masticatory forces during chewing and biting. Although such dissociations highlight selection to uncouple shared ancestral growth patterns, they occur largely via transpositions and retention of primitive size-shape covariation patterns or relative growth coefficients.

Allometry and evolution in the galago skull.

To probe the ontogenetic bases of morphological diversity across galagos, we performed the first clade-wide analyses of growth allometries in 564 adult and non-adult crania from 12 galagid taxa. In addition to evaluating if variation in galago skull form results from the differential extension/truncation of common ontogenetic patterns, scaling trajectories were employed as a criterion of subtraction to identify putative morphological adaptations in the feeding complex. A pervasive pattern of ontogenetic scaling is observed for facial dimensions across galagids, with 2 genera also sharing relative growth trajectories for masticatory proportions (Galago, Galagoides). As the facial growth series and adult data are largely coincidental, interspecific variation may result from character displacement and consequent selection for size differentiation among sister taxa. Derived configurations of the jaw joint and jaw muscle mechanical advantage in Otolemur and Euoticus appear to facilitate increased gape during scraping behaviors. Differences in aspects of masticatory growth and form characterizing these 2 genera highlight selection to uncouple shared ontogenetic patterns, which occurred via transpositions that retained ancestral scaling patterns. Due to the lack of increased robusticity of load-resisting mandibular elements in Otolemur and Euoticus, there is little evidence to suggest that exudativory in galagos results in correspondingly higher masticatory stresses.

Masticatory Loading and Ossification of the Mandibular Symphysis during Anthropoid Origins.

An ossified or 'fused' mandibular symphysis characterizes the origins of the Anthropoidea, a primate suborder that includes humans. Longstanding debate about the adaptive significance of variation in this jaw joint centers on whether a bony symphysis is stronger than an unfused one spanned by cartilage and ligaments. To provide essential information regarding mechanical performance, intact adult symphyses from representative primates and scandentians were loaded ex vivo to simulate stresses during biting and chewing - dorsoventral (DV) shear and lateral transverse bending ('wishboning'). The anthropoid symphysis requires significantly more force to induce structural failure vs. strepsirrhines and scandentians with unfused joints. In wishboning, symphyseal breakage always occurs at the midline in taxa with unfused conditions, further indicating that an ossified symphysis is stronger than an unfused joint. Greater non-midline fractures among anthropoids suggest that fusion imposes unique constraints on masticatory function elsewhere along the mandible, a phenomenon likely to characterize the evolution of fusion and jaw form throughout Mammalia.

Plasticity of mandibular biomineralization in myostatin-deficient mice.

Compared with the normal or wild-type condition, knockout mice lacking myostatin (Mstn), a negative regulator of skeletal muscle growth, develop significant increases in relative masticatory muscle mass as well as the ability to generate higher maximal muscle forces. Wild-type and myostatin-deficient mice were compared to assess the postweaning influence of elevated masticatory loads because of increased jaw-adductor muscle and bite forces on the biomineralization of mandibular cortical bone and dental tissues. Microcomputed tomography (microCT) was used to quantify bone density at a series of equidistant external and internal sites in coronal sections for two symphysis and two corpus locations. Discriminant function analyses and nonparametric ANOVAs were used to characterize variation in biomineralization within and between loading cohorts. Multivariate analyses indicated that 95% of the myostatin-deficient mice and 95% of the normal mice could be distinguished based on biomineralization values at both symphysis and corpus sections. At the corpus, ANOVAs suggest that between-group differences are due to the tendency for cortical bone mineralization to be higher in myostatin-deficient mice, coupled with higher levels of dental biomineralization in normal mice. At the symphysis, ANOVAs indicate that between-group differences are related to significantly elevated bone-density levels along the articular surface and external cortical bone in the knockout mice. Both patterns, especially those for the symphysis, appear because of the postweaning effects of increased masticatory stresses in the knockout mice versus normal mice. The greater number of symphyseal differences suggest that bone along this jaw joint may be characterized by elevated plasticity. Significant differences in bone-density levels between normal and myostatin-deficient mice, coupled with the multivariate differences in patterns of plasticity between the corpus and symphysis, underscore the need for a comprehensive analysis of the plasticity of masticatory tissues vis-à-vis altered mechanical loads.

Ontogenetic and functional modularity in the rodent mandible.

The material properties of diets consumed by juvenile individuals are known to affect adult morphological outcomes. However, much of the current experimental knowledge regarding dietary effects on masticatory form is derived from studies in which individuals are fed a non-variable diet for the duration of their postweaning growth period. Thus, it remains unclear how intra-individual variation in diet, due to ontogenetic variation in feeding behaviors or seasonal resource fluctuations, affects the resulting adult morphology. Furthermore, the mandible is composed of multiple developmental and functional subunits, and the extent to which growth and plasticity among these modules is correlated may be misestimated by studies that examine non-variable masticatory function in adults only. To address these gaps in our current knowledge, this study raised Sprague Dawley rats (n=42) in four dietary cohorts from weaning to skeletal maturity. Two cohorts were fed a stable ("annual") diet of either solid or powdered pellets. The other two cohorts were fed a variable ("seasonal") diet consisting of solid/powdered pellets for the first half of the study, followed by a shift to the opposite diet. Results of longitudinal morphometric analyses indicate that variation in the mandibular corpus is more prominent at immature ontogenetic stages, likely due to processes of dental eruption and the growth of tooth roots. Furthermore, adult morphology is influenced by both masticatory function and the ontogenetic timing of this function, e.g., the consumption of a mechanically resistant diet. The morphology of the coronoid process was found to separate cohorts on the basis of their early weanling diet, suggesting that the coronoid process/temporalis muscle module may have an early plasticity window related to high growth rates during this life stage. Conversely, the morphology of the angular process was found to be influenced by the consumption of a mechanically resistant diet at any point during the growth period, but with a tendency to reflect the most recent diet. The prolonged plasticity window of the angular process/pterygomasseteric muscle module may be related to delayed ossification and muscular maturation within this module. The research presented here highlights the importance of more naturalistic models of mammalian feeding, and underscores the need for a better understanding of the processes of both morphological and behavioral maturation that follow weaning.

Bone up: craniomandibular development and hard-tissue biomineralization in neonate mice.

The presence of regional variation in the osteogenic abilities of cranial bones underscores the fact that the mechanobiology of the mammalian skull is more complex than previously recognized. However, the relationship between patterns of cranial bone formation and biomineralization remains incompletely understood. In four strains of mice, micro-computed tomography was used to measure tissue mineral density during perinatal development in three skull regions (calvarium, basicranium, mandible) noted for variation in loading environment, embryological origin, and ossification mode. Biomineralization levels increased during perinatal ontogeny in the mandible and calvarium, but did not increase in the basicranium. Tissue mineral density levels also varied intracranially, with density in the mandible being highest, in the basicranium intermediate, and in the calvarium lowest. Perinatal increases in, and elevated levels of, mandibular biomineralization appear related to the impending postweaning need to resist elevated masticatory stresses. Similarly, perinatal increases in calvarial biomineralization may be linked to ongoing brain expansion, which is known to stimulate sutural bone formation in this region. The lack of perinatal increase in basicranial biomineralization could be a result of earlier developmental maturity in the cranial base relative to other skull regions due to its role in supporting the brain's mass throughout ontogeny. These results suggest that biomineralization levels and age-related trajectories throughout the skull are influenced by the functional environment and ontogenetic processes affecting each region, e.g., onset of masticatory loads in the mandible, whereas variation in embryology and ossification mode may only have secondary effects on patterns of biomineralization. Knowledge of perinatal variation in tissue mineral density, and of normal cranial bone formation early in development, may benefit clinical therapies aiming to correct developmental defects and traumatic injuries in the skull, and more generally characterize loading environments and skeletal adaptations in mammals by highlighting the need for multi-level analyses for evaluating functional performance of cranial bone.

Intracranial and hierarchical perspective on dietary plasticity in mammals.

The effect of dietary properties on craniofacial form has been the focus of numerous functional studies, with increasingly more work dedicated to the importance of phenotypic plasticity. As bone is a dynamic tissue, morphological variation related to differential loading is well established for many masticatory structures. However, the adaptive osteogenic response of several cranial sites across multiple levels of bony organization remains to be investigated. Here, rabbits were obtained at weaning and raised for 48 weeks until adulthood in order to address the naturalistic influence of altered loading on the long-term development of masticatory and non-masticatory elements. Longitudinal data from micro-computed tomography (µCT) scans were used to test the hypothesis that variation in cortical bone formation and biomineralization in masticatory structures is linked to increased stresses during oral processing of mechanically challenging foods. It was also hypothesized that similar parameters for neurocranial structures would be minimally affected by varying loads as this area is characterized by low strains during mastication and reduced hard-tissue mechanosensitivity. Hypotheses were supported regarding bone formation for maxillomandibular and neurocranial elements, though biomineralization trends of masticatory structures did not mirror macroscale findings. Varying osteogenic responses in masticatory elements suggest that physiological adaptation, and corresponding variation in skeletal performance, may reside differentially at one level of bony architecture, potentially affecting the accuracy of behavioral and in silico reconstructions. Together, these findings underscore the complexity of bone adaptation and highlight functional and developmental variation in determinants of skull form.

Biomineralization and adaptive plasticity of the temporomandibular joint in myostatin knockout mice.

Mice lacking myostatin (GDF-8), a negative regulator of skeletal muscle growth, show a significant increase in muscle mass versus normal mice. We compared wild-type and myostatin deficient mice to assess the postnatal effect of elevated masticatory loads due to increased jaw-adductor muscle activity and greater bite forces on mandibular condyle morphology. Microcomputed tomography (microCT) was used to provide details of internal condylar morphology and quantify bone density in three condylar regions. Biomineralization levels, as well as external mandibular dimensions, were used to characterize within-slice, within-joint, within-group and between-group variation. Dimensions of the mandible and mandibular condyle were similar between the myostatin knockout and normal mice. Knockout mice exhibited significantly more biomineralization on the outer surface of the condylar subchondral bone and along the condylar neck, most notably on the buccal side of the condylar neck. The buccal side of the inner aspect of the condyle was significantly less biomineralized in knockout mice, both for the pooled data and for the posterior and anterior condylar slices. Whilst normal mice had symmetric subchondral bone surfaces, those of knockout mice were asymmetric, with a lower, less convex surface on the buccal side versus the lingual side. This appears related to the ontogenetic effects of increased masticatory stress in the mandibles of knockout mice as compared to normal mice. Significant differences in biomineralization between normal and myostatin knockout mice, coupled with the lack of significant differences in certain external dimensions, underscores a need for information on the external and internal morphology of mineralized tissues vis-à-vis altered or excessive mechanical loads.

Betwixt and Between: Intracranial Perspective on Zygomatic Arch Plasticity and Function in Mammals.

The zygomatic arch is morphologically complex, providing a key interface between the viscerocranium and neurocranium. It also serves as an attachment site for masticatory muscles, thereby linking it to the feeding apparatus. Though morphological variation related to differential loading is well known for many craniomandibular elements, the adaptive osteogenic response of the zygomatic arch remains to be investigated. Here, experimental data are presented that address the naturalistic influence of masticatory loading on the postweaning development of the zygoma and other cranial elements. Given the similarity of bone-strain levels among the zygoma and maxillomandibular elements, a rabbit and pig model were used to test the hypothesis that variation in cortical bone formation and biomineralization along the zygomatic arch and masticatory structures are linked to increased stresses. It was also hypothesized that neurocranial structures would be minimally affected by varying loads. Rabbits and pigs were raised for 48 weeks and 8 weeks, respectively. In both experimental models, CT analyses indicated that elevated masticatory loading did not induce differences in cortical bone thickness of the zygomatic arch, though biomineralization was positively affected. Hypotheses were supported regarding bone formation for maxillomandibular and neurocranial elements. Varying osteogenic responses in the arch suggests that skeletal adaptation, and corresponding variation in performance, may reside differentially at one level of bony architecture. Thus, it is possible that phenotypic diversity in the mammalian zygoma is due more singularly to natural selection (vs. plasticity). These findings underscore the complexity of the zygomatic arch and, more generally, determinants of skull form. Anat Rec, 299:1646-1660, 2016. © 2016 Wiley Periodicals, Inc.

Chewed out: an experimental link between food material properties and repetitive loading of the masticatory apparatus in mammals.

Using a model organism (rabbits) that resembles a number of mammalian herbivores in key aspects of its chewing behaviors, we examined how variation in dietary mechanical properties affects food breakdown during mastication. Such data have implications for understanding phenotypic variation in the mammalian feeding apparatus, particularly with respect to linking jaw form to diet-induced repetitive loading. Results indicate that chewing frequency (chews/s) is independent of food properties, whereas chewing investment (chews/g) and chewing duration(s), which are proportional to repetitive loading of the jaws, are positively related to food stiffness and toughness. In comparisons of displacement-limited and stress-limited fragmentation indices, which respectively characterize the intraoral breakdown of tough and stiff foods, increases in chewing investment and duration are linked solely to stiffness. This suggests that stiffer foods engender higher peak loads and increased cyclical loading. Our findings challenge conventional wisdom by demonstrating that toughness does not, by itself, underlie increases in cyclical loading and loading duration. Instead, tough foods may be associated with such jaw-loading patterns because they must be processed in greater volumes owing to their lower nutritive quality and for longer periods of time to increase oral exposure to salivary chemicals.

Craniodental allometry and heterochrony in two howler monkeys: Alouatta seniculus and A. palliata.

Cranial dimensions were collected from growth series for two sexually dimorphic congeners: Alouatta seniculus, the red howler monkey, and Alouatta palliata, the mantled howler monkey. In both A. seniculus and A. palliata, ontogenetic series for males and females were compared to evaluate if sexual dimorphism in skull form results from the differential extension of common patterns of relative growth. Subsequently, growth series for both species were compared to investigate whether morphological differences between species also result from the ontogenetic scaling of cranial proportions. Analyses indicate that cranial proportions for both sexes of Alouatta palliata are ontogenetically scaled. In mantled howlers, males apparently reach larger terminal size by growing for a longer duration and, to a lesser extent, at a faster rate than females. Data for both sexes of Alouatta seniculus indicate that cranial proportions are also ontogenetically scaled. In particular, male red howlers apparently reach larger adult size by growing at a faster rate and, perhaps, to an equivalent or longer duration than females. The Alouatta seniculus data underscore apparent differences in the rate and timing components of sex dimorphism, possibly due to sexual differences among dental eruption patterns, cranial development, somatic growth, and socioecological factors. Results for both species indicate that intrasexual selection for size differentiation has a minimal effect on brain size and postcanine tooth size dimorphism. Lastly, comparisons of allometric trajectories for both species further demonstrate a strong pattern of ontogenetic scaling of cranial proportions. © 1994 Wiley-Liss, Inc.

On the reversibility of mandibular symphyseal fusion.

Experimental and comparative studies suggest that a major determinant of increased ossification of the mandibular symphysis is elevated masticatory stress related to a mechanically challenging diet. However, the morphology of this joint tracks variation in dietary properties in only some mammalian clades. Extant anthropoid primates are a notable exception: synostosis is ubiquitous in this speciose group, despite its great age and diverse array of feeding adaptations. One possible explanation for this pattern is that, once synostosis evolves, reversion to a lesser degree of fusion is unlikely or even constrained. If correct, this has important implications for functional and phylogenetic analyses of the mammalian feeding apparatus. To test this hypothesis, we generated a molecular tree for 76 vespertilionoid and noctilionoid chiropterans using Bayesian phylogenetic analysis and examined character evolution using parsimony and likelihood ancestral-state reconstructions along with the binary state speciation and extinction (BiSSE) model. Results indicate that reversals have occurred within Vespertilionoidea. In contrast, noctilionoids exhibit an anthropoid-like pattern, which suggests that more detailed comparisons of the functional and developmental bases for fusion in these bat clades may provide insight into why fusion is maintained in some lineages but not in others. Potential functional and developmental explanations for the lack of reversal are discussed.

Bisphosphonate effects on the behaviour of oral epithelial cells and oral fibroblasts.

OBJECTIVE: Bisphosphonates (BPs) like Zometa (ZA) are widely used to treat complications of bony metastases in cancer patients. A serious adverse event occurs in 1-12% of patients on BP therapy, osteonecrosis of the jaw (BPONJ). BPONJ develops after oral trauma and is manifested by poor wound healing and soft-tissue breakdown followed by exposure and necrosis of intra-oral bone. Currently, there is no effective clinical treatment for BPONJ. DESIGN: We evaluated the effect of ZA on the proliferation, apoptosis and migratory capacity of the cell lines CRL-7408, an oral fibroblast culture and OKF/6, an oral epithelial cell line. RESULTS: In both oral epithelium and fibroblasts, ZA exposure inhibited proliferation and elevated apoptosis; however oral fibroblasts were differentially influenced versus oral epithelial cells. In oral fibroblasts, ZA treatment significantly inhibited motility. Further, quantitative real-time PCR demonstrated that ZA treatment of oral fibroblasts inhibits expression of both the COL1A1 and COL1A2 chains of type-I collagen, consistent with a loss of collagen immunofluorescent staining. CONCLUSIONS: These data support a model wherein ZA treatment impedes oral wound healing by blocking the growth and migratory capacity of oral fibroblasts as well as downregulating the transcription of type-I collagen, functions necessary to deposit the granulation tissue needed for re-epithelization. Therefore, BP released from bone following tooth extraction may delay wound healing of the oral mucosal barrier and contribute to BPONJ pathogenesis.