Functional anatomy of the wing muscles of the Egyptian fruit bat (Rousettus aegyptiacus) using dissection and diceCT.

Bats are unique among mammals for evolving powered flight. However, very little data are available on the muscle properties and architecture of bat flight muscles. Diffusible iodine contrast-enhanced computed tomography (diceCT) is an established tool for 3D visualisation of anatomy and is becoming a more readily accessible and widely used technique. Here, we combine this technique with gross dissection of the Egyptian fruit bat (Rousettus aegyptiacus) to compare muscle masses, fibre lengths and physiological cross-sectional areas (PCSA) of muscles with published forelimb data from an array of non-flying mammals and flying birds. The Egyptian fruit bat has a highly specialised pectoralis (pars posterior) architecturally optimised to generate power. The elbow flexion/extension muscles (biceps brachii and triceps brachii) have comparable PCSAs to the pectoralis, but shorter fibre lengths, which are optimised to generate large forces. Our data also show that the Egyptian fruit bat is more similar to flying birds than non-flying mammals with its highly disparate muscle architecture. Specifically, the Egyptian fruit bat have uniquely enlarged pectoralis muscles and elbow flexion and extension muscles (bicep brachii and triceps brachii) to aid powered flight. Finally, while the Egyptian fruit bat has a comparable heterogeneity in pectoralis (pars posterior) fibre length across the cranial-caudal axis to that seen in birds, the average normalised fibre length is larger than that seen in any of the surveyed birds. Our data here provide a greater understanding of the anatomy and functional specialisation of the forelimb musculature that powers flight.

Comparative cranial biomechanics in two lizard species: impact of variation in cranial design.

Cranial morphology in lepidosaurs is highly disparate and characterised by the frequent loss or reduction of bony elements. In varanids and geckos, the loss of the postorbital bar is associated with changes in skull shape, but the mechanical principles underlying this variation remain poorly understood. Here, we sought to determine how the overall cranial architecture and the presence of the postorbital bar relate to the loading and deformation of the cranial bones during biting in lepidosaurs. Using computer-based simulation techniques, we compared cranial biomechanics in the varanid Varanus niloticus and the teiid Salvator merianae, two large, active foragers. The overall strain magnitude and distribution across the cranium were similar in the two species, despite lower strain gradients in V. niloticus In S. merianae, the postorbital bar is important for resistance of the cranium to feeding loads. The postorbital ligament, which in varanids partially replaces the postorbital bar, does not affect bone strain. Our results suggest that the reduction of the postorbital bar impaired neither biting performance nor the structural resistance of the cranium to feeding loads in V. niloticus Differences in bone strain between the two species might reflect demands imposed by feeding and non-feeding functions on cranial shape. Beyond variation in cranial bone strain related to species-specific morphological differences, our results reveal that similar mechanical behaviour is shared by lizards with distinct cranial shapes. Contrary to the situation in mammals, the morphology of the circumorbital region, calvaria and palate appears to be important for withstanding high feeding loads in these lizards.

Individual variation of the masticatory system dominates 3D skull shape in the herbivory-adapted marsupial wombats.

BACKGROUND: Within-species skull shape variation of marsupial mammals is widely considered low and strongly size-dependent (allometric), possibly due to developmental constraints arising from the altricial birth of marsupials. However, species whose skulls are impacted by strong muscular stresses - particularly those produced through mastication of tough food items - may not display such intrinsic patterns very clearly because of the known plastic response of bone to muscle activity of the individual. In such cases, allometry may not dominate within-species shape variation, even if it is a driver of evolutionary shape divergence; ordination of shape in a geometric morphometric context through principal component analysis (PCA) should reveal main variation in areas under masticatory stress (incisor region/zygomatic arches/mandibular ramus); but this main variation should emerge from high individual variability and thus have low eigenvalues. RESULTS: We assessed the evidence for high individual variation through 3D geometric morphometric shape analysis of crania and mandibles of three species of grazing-specialized wombats, whose diet of tough grasses puts considerable strain on their masticatory system. As expected, we found little allometry and low Principal Component 1 (PC1) eigenvalues within crania and mandibles of all three species. Also as expected, the main variation was in the muzzle, zygomatic arches, and masticatory muscle attachments of the mandibular ramus. We then implemented a new test to ask if the landmark variation reflected on PC1 was reflected in individuals with opposite PC1 scores and with opposite shapes in Procrustes space. This showed that correspondence between individual and ordinated shape variation was limited, indicating high levels of individual variability in the masticatory apparatus. DISCUSSION: Our results are inconsistent with hypotheses that skull shape variation within marsupial species reflects a constraint pattern. Rather, they support suggestions that individual plasticity can be an important determinant of within-species shape variation in marsupials (and possibly other mammals) with high masticatory stresses, making it difficult to understand the degree to which intrinsic constraints act on shape variation at the within-species level. We conclude that studies that link micro- and macroevolutionary patterns of shape variation might benefit from a focus on species with low-impact mastication, such as carnivorous or frugivorous species.

Impact of Medicaid Expansion on Access to Opioid Analgesic Medications and Medication-Assisted Treatment.

OBJECTIVES: To assess the impact of the expansion of Medicaid eligibility in the United States on the opioid epidemic, as measured through increased access to opioid analgesic medications and medication-assisted treatment. METHODS: Using Medicaid enrollment and reimbursement data from 2011 to 2016 in all states, we evaluated prescribing patterns of opioids and the 3 Food and Drug Administration-approved medications used in treating opioid use disorders by using 2 statistical models. We used difference-in-differences and interrupted time series models to measure prescribing rates before and after state expansions. RESULTS: Although opioid prescribing per Medicaid enrollee increased overall, we observed no statistical difference between expansion and nonexpansion states. By contrast, per-enrollee rates of buprenorphine and naltrexone prescribing increased more than 200% after states expanded eligibility, while increasing by less than 50% in states that did not expand. Methadone prescribing decreased in all states in this period, with larger decreases in expansion states. CONCLUSIONS: The Medicaid expansion enrolled a population no more likely to be prescribed opioids than the base Medicaid population while significantly increasing uptake of 2 drugs used in medication-assisted treatment.

Mapping the impact of the expanded Mexico City Policy for HIV/ family planning service integration in PEPFAR-supported countries: a risk index.

BACKGROUND: The previously-named Mexico City Policy (MCP) - which prohibited non U.S.-based non-governmental organizations (NGOs) from receiving U.S. family planning (FP) funding if they advocated, provided, counseled, or referred clients for abortions, even with non-U.S. funds - was reinstated and expanded in 2017. For the first time, the expanded MCP (EMCP) applies to HIV funding through the President's Emergency Plan for AIDS Relief (PEPFAR) in addition to FP funding. Previous, and more limited, iterations of the policy forced clinic closures and decreased contraceptive access, prompting the need to examine where and how the EMCP may impact FP/HIV service integration. METHODS: The likelihood of FP/HIV service de-integration under the EMCP was quantified using a composite risk index for 31 PEPFAR-funded countries. The index combines six standardized indicators from publically available sources organized into three sub-indexes: 1) The importance of PEPFAR for in-country service delivery of HIV and FP services; 2) The susceptibility of implementing partners to the EMCP; and 3) The integration of FP/HIV funds and programming through PEPFAR and USAID. RESULTS: Countries with the highest overall risk scores included Zambia (3.3) Cambodia (3.2), Uganda (3.1), South Africa (2.9), Haiti (2.8), Lesotho (2.8), Swaziland (2.1), and Burundi (1.5). Zambia's risk score is driven by sub-index 1, having a high proportion of country HIV expenditures provided by PEPFAR (86.3%). Cambodia and Uganda's scores are driven sub-index 3, with both countries reporting 100% of PEPFAR supported HIV delivery sites were providing integrated FP services in 2017. South Africa's risk score is driven by sub-index 2, where roughly 60% of PEPFAR funding is to non U.S.-based NGOs. Of the countries with the highest risk scores, Swaziland, Lesotho, and South Africa, are also in the top quartile of PEPFAR countries for HIV prevalence and unintended pregnancies among young women. CONCLUSION: This analysis highlights where and why the EMCP may have the greatest impact on FP/HIV service integration. The possible disruption of service integration in countries with generalized HIV epidemics highlights significant risks. Researchers, national governments, and non-U.S. funders can consider these risk factors to help target their responses to the EMCP and mitigate potential harms of the policy.

Assessing healthcare quality using routine data: evaluating the performance of the national tuberculosis programme in South Africa.

OBJECTIVE: To assess the performance of healthcare facilities by means of indicators based on guidelines for clinical care of TB, which is likely a good measure of overall facility quality. METHODS: We assessed quality of care in all public health facilities in South Africa using graphical, correlation and locally weighted kernel regression analysis of routine TB test data. RESULTS: Facility performance falls short of national standards of care. Only 74% of patients with TB provided a second specimen for testing, 18% received follow-up testing and 14% received drug resistance testing. Only resistance testing rates improved over time, tripling between 2004 and 2011. National awareness campaigns and changes in clinical guidelines had only a transient impact on testing rates. The poorest performing facilities remained at the bottom of the rankings over the period of study. CONCLUSION: The optimal policy strategy requires both broad-based policies and targeted resources to poor performers. This approach to assessing facility quality of care can be adapted to other contexts and also provides a low-cost method for evaluating the effectiveness of proposed interventions. Devising targeted policies based on routine data is a cost-effective way to improve the quality of public health care provided.

Cranial biomechanics, bite force and function of the endocranial sinuses in Diprotodon optatum, the largest known marsupial.

The giant extinct marsupial Diprotodon optatum has unusual skull morphology for an animal of its size, consisting of very thin bone and large cranial sinuses that occupy most of the internal cranial space. The function of these sinuses is unknown as there are no living marsupial analogues. The finite element method was applied to identify areas of high and low stress, and estimate the bite force of Diprotodon to test hypotheses on the function of the extensive cranial sinuses. Detailed three-dimensional models of the cranium, mandible and jaw adductor muscles were produced. In addition, manipulations to the Diprotodon cranial model were performed to investigate changes in skull and sinus structure, including a model with no sinuses (sinuses 'filled' with bone) and a model with a midsagittal crest. Results indicate that the cranial sinuses in Diprotodon significantly lighten the skull while still providing structural support, a high bite force and low stress, indicating the cranium may have been able to withstand higher loads than those generated during feeding. Data from this study support the hypothesis that pneumatisation is driven by biomechanical loads and occurs in areas of low stress. The presence of sinuses is likely to be a byproduct of the separation of the outer surface of the skull from the braincase due to the demands of soft tissue including the brain and the large jaw adductor musculature, especially the temporalis. In very large species, such as Diprotodon, this separation is more pronounced, resulting in extensive cranial sinuses due to a relatively small brain compared with the size of the skull.

Does directly observed therapy improve tuberculosis treatment? More evidence is needed to guide tuberculosis policy.

BACKGROUND: Tuberculosis (TB) now ranks alongside HIV as the leading infectious disease cause of death worldwide and incurs a global economic burden of over $12 billion annually. Directly observed therapy (DOT) recommends that TB patients complete the course of treatment under direct observation of a treatment supporter who is trained and overseen by health services to ensure that patients take their drugs as scheduled. Though the current WHO End TB Strategy does not mention DOT, only "supportive treatment supervision by treatment partners", many TB programs still use it despite the fact that the has not been demonstrated to be statistically significantly superior to self-administered treatment in ensuring treatment success or cure. DISCUSSION: DOT is designed to promote proper adherence to the full course of drug therapy in order to improve patient outcomes and prevent the development of drug resistance. Yet over 8 billion dollars is spent on TB treatment each year and thousands undergo DOT for all or part of their course of treatment, despite the absence of rigorous evidence supporting the superior effectiveness of DOT over self-administration for achieving drug susceptible TB (DS-TB) cure. Moreover, the DOT component burdens patients with financial and opportunity costs, and the potential for intensified stigma. To rigorously evaluate the effectiveness of DOT and identify the essential contributors to both successful treatment and minimized patient burden, we call for a pragmatic experimental trial conducted in real-world program settings, the gold standard for evidence-based health policy decisions. It is time to invest in the rigorous evaluation of DOT and reevaluate the DOT requirement for TB treatment worldwide. Rigorously evaluating the choice of treatment supporter, the frequency of health care worker contact and the development of new educational materials in a real-world setting would build the evidence base to inform the optimal design of TB treatment protocol. Implementing a more patient-centered approach may be a wise reallocation of resources to raise TB cure rates, prevent relapse, and minimize the emergence of drug resistance. Maintaining the status quo in the absence of rigorous supportive evidence may diminish the effectiveness of TB control policies in the long run.

The opossum MHC genomic region revisited.

The gray short-tailed opossum Monodelphis domestica is one of the few marsupial species for which a high quality whole genome sequence is available and the major histocompatibility complex (MHC) region has been annotated. Previous analyses revealed only a single locus within the opossum MHC region, designated Modo-UA1, with the features expected for encoding a functionally classical class I α-chain. Nine other class I genes found within the MHC are highly divergent and have features usually associated with non-classical roles. The original annotation, however, was based on an early version of the opossum genome assembly. More recent analyses of allelic variation in individual opossums revealed too many Modo-UA1 sequences per individual to be accounted for by a single MHC class I locus found in the genome assembly. A reanalysis of a later generation assembly, MonDom5, revealed the presence of two additional loci, now designated Modo-UA3 and UA4, in a region that was expanded and more complete than in the earlier assembly. Modo-UA1, UA3, and UA4 are all transcribed, although Modo-UA4 transcripts are rarer. Modo-UA4 is also relatively non-polymorphic. Evidence presented support the accuracy of the later assembly and the existence of three related class I genes in the opossum, making opossums more typical of mammals and most tetrapods by having multiple apparent classical MHC class I loci.

Comparative finite element analysis of the first thoracic vertebra in artiodactyls.

Artiodactyls exhibit a striking diversity of the cervical vertebral column in terms of length and overall mobility. Using finite element analysis, this study explores the morphology at the cervico-thoracic boundary and its performance under loads in artiodactyls with different habitual neck postures and body sizes. The first thoracic vertebra of 36 species was loaded with (i) a compressive load on the vertebral body to model the weight of the head and neck exerted onto the trunk; and (ii) a tensile load at the spinous process to model the pull via the nuchal ligament. Additional focus was laid on the peculiar shape of the first thoracic vertebra in giraffes. We hypothesized that a habitually upright neck posture should be reflected in the greater ability to withstand compressive loads compared to tensile loads, whereas for species with a habitually suspended posture it should be the opposite. In comparison to species with a suspended posture, species with an upright posture exhibited lower stress (except Giraffidae). For compressive loads in larger species, stress surprisingly increased. Tensile loads in larger species resulted in decreased stress only in species with an intermediate or suspensory neck posture. High stress under tensile loads was mainly reflecting the relative length of the spinous process, while high stress under compressive loads was common in more "bell"-shaped vertebral bodies. The data supports a stability-mobility trade-off at the cervico-thoracic transition in giraffes. Performance under load at the cervico-thoracic boundary is indicative of habitual neck posture and is influenced by body size.

Facilitators and barriers to community-led monitoring of health programs: Qualitative evidence from the global implementation landscape.

Achieving the global HIV, tuberculosis, and malaria targets will require innovative strategies to deliver high quality and person-centered health services. Community-led monitoring (CLM) is a rapidly proliferating health systems strengthening intervention for improving healthcare services and documenting human rights violations, through social empowerment and political accountability. Driven in part by increasing financial support from donors, a growing number of countries are implementing CLM programs. This study aimed to identify early challenges and lessons learned from CLM implementation, with the aim of informing and improving the implementation of CLM programs and ultimately achieving greater impact on the delivery of services. Twenty-five CLM implementors representing 21 countries participated in an interview. Early generation of buy-in from diverse stakeholders was noted as critical for CLM success. Leveraging existing networks of service users and community organizations to implement CLM also helped to maximize program reach and resources. Uncertainty around CLM's purpose and roles among CLM stakeholders resulted in challenges to community leadership and ownership of programs. Respondents also described challenges with underfunded programs, especially advocacy components, and inflexible donor funding mechanisms. Critical capacity gaps remain around advocacy and electronic data collection and use. With the rapid expansion of CLM, this study serves as an important first step in characterizing challenges and successes in the CLM landscape. Successful implementation of CLM requires prioritizing community ownership and leadership, donor commitment to sustainable and reliable funding, and strengthened support of programs across the data collection and advocacy lifecycle.

Drivers of HIV treatment interruption: Early findings from community-led monitoring program in Haiti.

BACKGROUND: Failure to retain people living with HIV (PLHIV) in care remains a significant barrier to achieving epidemic control in Haiti, with as many as 30% lost from care within one year of starting treatment. Community-led monitoring (CLM) is an emerging approach of improving healthcare and accountability to service users, through a cycle of monitoring and advocacy. In 2020, a CLM program was launched in Haiti to identify barriers to retention and advocating for better health services. METHODS: Data from the community-led monitoring program in Haiti were analyzed, from a sample of 65 healthcare facilities in the Nord, Artibonite, and Ouest departments collected from April 2021 to February 2022. Qualitative data from six community-based focus groups and 45 semi-structured individual interviews were analyzed. RESULTS: Confidentiality and stigmatization emerged as barriers to care, particularly due to the separation of PLHIV from other patients in view of community members. To avoid identification, patients described traveling long distances, with the reimbursement of transportation costs described as being insufficient or unavailable. Costs of non-HIV clinical services were a frequent concern and respondents described a need for clinics to provide food during all patient visits. Stock-outs were a regular challenge; by contrast, treatment literacy did not emerge as a major barrier to retention. CONCLUSIONS: These findings represent the first instance, to our knowledge, of original data from a community-led monitoring program being published in any country. These findings suggest that improving treatment retention for PLHIV is dependent on improving the acceptability and affordability of healthcare services. Ensuring confidentiality is critical, particularly where stigma is high. Retention could be improved by systematically strengthening patient confidentiality protections throughout the healthcare system, providing patients with sufficient travel compensation and other incentives, and delivering wraparound services provided for free. Addressing these challenges will require ongoing advocacy for community-developed recommendations and solutions.

Assessment of the mechanical role of cranial sutures in the mammalian skull: Computational biomechanical modelling of the rat skull.

Cranial sutures are fibrocellular joints between the skull bones that are progressively replaced with bone throughout ontogeny, facilitating growth and cranial shape change. This transition from soft tissue to bone is reflected in the biomechanical properties of the craniofacial complex. However, the mechanical significance of cranial sutures has only been explored at a few localised areas within the mammalian skull, and as such our understanding of suture function in overall skull biomechanics is still limited. Here, we sought to determine how the overall strain environment is affected by the complex network of cranial sutures in the mammal skull. We combined two computational biomechanical methods, multibody dynamics analysis and finite element analysis, to simulate biting in a rat skull and compared models with and without cranial sutures. Our results show that including complex sutures in the rat model does not substantially change overall strain gradients across the cranium, particularly strain magnitudes in the bones overlying the brain. However, local variations in strain magnitudes and patterns can be observed in areas close to the sutures. These results show that, during feeding, sutures may be more important in some regions than others. Sutures should therefore be included in models that require accurate local strain magnitudes and patterns of cranial strain, particularly if models are developed for analysis of specific regions, such as the temporomandibular joint or zygomatic arch. Our results suggest that, for mammalian skulls, cranial sutures might be more important for allowing brain expansion during growth than redistributing biting loads across the cranium in adults.

The evolution of unique cranial traits in leporid lagomorphs.

Background: The leporid lagomorphs (rabbits and hares) are adapted to running and leaping (some more than others) and consequently have unique anatomical features that distinguish them from ochotonid lagomorphs (pikas) and from their rodent relatives. Two traits that have received some attention are fenestration of the lateral wall of the maxilla and facial tilting. These features are known to correlate with specialised locomotory form in that the faster running species will generally have fenestration that occupies the dorsal and the anteroventral surface of the maxillary corpus and a more acute facial tilt angle. Another feature is an intracranial joint that circumscribes the back of the skull, thought to facilitate skull mobility. This joint separates the anterior portion of the cranium (including the dentition, rostrum and orbit) from the posterior portion of the cranium (which encompasses the occipital and the auditory complex). Aside from the observation that the intracranial joint is absent in pikas (generalist locomotors) and appears more elaborate in genera with cursorial and saltatorial locomotory habits, the evolutionary history, biomechanical function and comparative anatomy of this feature in leporids lacks a comprehensive evaluation. Methodology: The present work analysed the intracranial joint, facial tilting and lateral fenestration of the wall of the maxilla in the context of leporid evolutionary history using a Bayesian inference of phylogeny (18 genera, 23 species) and ancestral state reconstruction. These methods were used to gather information about the likelihood of the presence of these three traits in ancestral groups. Results: Our phylogenetic analyses found it likely that the last common ancestor of living leporids had some facial tilting, but that the last common ancestor of all lagomorphs included in the dataset did not. We found that it was likely that the last common ancestor of living leporids had fenestration that occupies the dorsal, but not the anteroventral, surface of the maxillary corpus. We also found it likely that the last common ancestor of living leporids had an intracranial joint, but that the last common ancestor of all living lagomorphs did not. These findings provide a broader context to further studies of evolutionary history and will help inform the formulation and testing of functional hypotheses.

Anomalous plantar intrinsic foot muscle attaching to the medial longitudinal arch: possible mechanism for medial nerve entrapment: a case report.

BACKGROUND: Muscular variations are potentially symptomatic and may complicate imaging interpretation. Intrinsic foot musculature and extrinsic tendon insertion variations are common. Distinct supernumerary muscles are rare. We report a novel anomalous intrinsic foot muscle on the medial longitudinal arch. CASE PRESENTATION: An accessory muscle was encountered on the medial arch of the right foot of a 78-year-old white male cadaver, between layers two and three of the foot intrinsics. It did not appear to be a slip or variant of a known foot muscle. This muscle consisted of two slips that ran transversely on the plantar aspect of the medial arch, crossing the medial transverse tarsal joint and attaching to the tuberosity of the navicular, the short and long plantar ligaments, and spring ligament. CONCLUSIONS: The medial plantar vessels and nerve passed from deep to superficial between the two slips, and this suggests a possible location for medial nerve entrapment.

Computational biomechanical modelling of the rabbit cranium during mastication.

Although a functional relationship between bone structure and mastication has been shown in some regions of the rabbit skull, the biomechanics of the whole cranium during mastication have yet to be fully explored. In terms of cranial biomechanics, the rabbit is a particularly interesting species due to its uniquely fenestrated rostrum, the mechanical function of which is debated. In addition, the rabbit processes food through incisor and molar biting within a single bite cycle, and the potential influence of these bite modes on skull biomechanics remains unknown. This study combined the in silico methods of multi-body dynamics and finite element analysis to compute musculoskeletal forces associated with a range of incisor and molar biting, and to predict the associated strains. The results show that the majority of the cranium, including the fenestrated rostrum, transmits masticatory strains. The peak strains generated over all bites were found to be attributed to both incisor and molar biting. This could be a consequence of a skull shape adapted to promote an even strain distribution for a combination of infrequent incisor bites and cyclic molar bites. However, some regions, such as the supraorbital process, experienced low peak strain for all masticatory loads considered, suggesting such regions are not designed to resist masticatory forces.

Global elongation and high shape flexibility as an evolutionary hypothesis of accommodating mammalian brains into skulls.

Little is known about how the large brains of mammals are accommodated into the dazzling diversity of their skulls. It has been suggested that brain shape is influenced by relative brain size, that it evolves or develops according to extrinsic or intrinsic mechanical constraints, and that its shape can provide insights into its proportions and function. Here, we characterize the shape variation among 84 marsupial cranial endocasts of 57 species including fossils, using three-dimensional geometric morphometrics and virtual dissections. Statistical shape analysis revealed four main patterns: over half of endocast shape variation ranges from elongate and straight to globular and inclined; little allometric variation with respect to centroid size, and none for relative volume; no association between locomotion and endocast shape; limited association between endocast shape and previously published histological cortex volumes. Fossil species tend to have smaller cerebral hemispheres. We find divergent endocast shapes in closely related species and within species, and diverse morphologies superimposed over the main variation. An evolutionarily and individually malleable brain with a fundamental tendency to arrange into a spectrum of elongate-to-globular shapes-possibly mostly independent of brain function-may explain the accommodation of brains within the enormous diversity of mammalian skull form.

Clarifying relationships between cranial form and function in tapirs, with implications for the dietary ecology of early hominins.

Paleontologists and paleoanthropologists have long debated relationships between cranial morphology and diet in a broad diversity of organisms. While the presence of larger temporalis muscle attachment area (via the presence of sagittal crests) in carnivorans is correlated with durophagy (i.e. hard-object feeding), many primates with similar morphologies consume an array of tough and hard foods-complicating dietary inferences of early hominins. We posit that tapirs, large herbivorous mammals showing variable sagittal crest development across species, are ideal models for examining correlations between textural properties of food and sagittal crest morphology. Here, we integrate dietary data, dental microwear texture analysis, and finite element analysis to clarify the functional significance of the sagittal crest in tapirs. Most notably, pronounced sagittal crests are negatively correlated with hard-object feeding in extant, and several extinct, tapirs and can actually increase stress and strain energy. Collectively, these data suggest that musculature associated with pronounced sagittal crests-and accompanied increases in muscle volume-assists with the processing of tough food items in tapirs and may yield similar benefits in other mammals including early hominins.

The multiscale hierarchical structure of Heloderma suspectum osteoderms and their mechanical properties.

Osteoderms are hard tissues embedded in the dermis of vertebrates and have been suggested to be formed from several different mineralized regions. However, their nano architecture and micro mechanical properties had not been fully characterized. Here, using electron microscopy, µ-CT, atomic force microscopy and finite element simulation, an in-depth characterization of osteoderms from the lizard Heloderma suspectum, is presented. Results show that osteoderms are made of three different mineralized regions: a dense apex, a fibre-enforced region comprising the majority of the osteoderm, and a bone-like region surrounding the vasculature. The dense apex is stiff, the fibre-enforced region is flexible and the mechanical properties of the bone-like region fall somewhere between the other two regions. Our finite element analyses suggest that when combined into the osteoderm structure, the distinct tissue regions are able to shield the body of the animal by bearing the external forces. These findings reveal the structure-function relationship of the Heloderma suspectum osteoderm in unprecedented detail. STATEMENT OF SIGNIFICANCE: The structures of bone and teeth have been thoroughly investigated. They provide a basis not only for understanding the mechanical properties and functions of these hard tissues, but also for the de novo design of composite materials. Osteoderms, however, are hard tissues that must possess mechanical properties distinct from teeth and bone to function as a protective armour. Here we provide a detailed analysis of the nanostructure of vertebrate osteoderms from Heloderma suspectum, and show that their mechanical properties are determined by their multiscale hierarchical tissue. We believe this study contributes to advance the current knowledge of the structure-function relationship of the hierarchical structures in the Heloderma suspectum osteoderm. This knowledge might in turn provide a source of inspiration for the design of bioinspired and biomimetic materials.

Comparative genomic analysis and evolution of the T cell receptor loci in the opossum Monodelphis domestica.

BACKGROUND: All jawed-vertebrates have four T cell receptor (TCR) chains: alpha (TRA), beta (TRB), gamma (TRG) and delta (TRD). Marsupials appear unique by having an additional TCR: mu (TRM). The evolutionary origin of TRM and its relationship to other TCR remain obscure, and is confounded by previous results that support TRM being a hybrid between a TCR and immunoglobulin locus. The availability of the first marsupial genome sequence allows investigation of these evolutionary relationships. RESULTS: The organization of the conventional TCR loci, encoding the TRA, TRB, TRG and TRD chains, in the opossum Monodelphis domestica are highly conserved with and of similar complexity to that of eutherians (placental mammals). There is a high degree of conserved synteny in the genomic regions encoding the conventional TCR across mammals and birds. In contrast the chromosomal region containing TRM is not well conserved across mammals. None of the conventional TCR loci contain variable region gene segments with homology to those found in TRM; rather TRM variable genes are most similar to that of immunoglobulin heavy chain genes. CONCLUSION: Complete genomic analyses of the opossum TCR loci continue to support an origin of TRM as a hybrid between a TCR and immunoglobulin locus. None of the conventional TCR loci contain evidence that such a recombination event occurred, rather they demonstrate a high degree of stability across distantly related mammals. TRM, therefore, appears to be derived from receptor genes no longer extant in placental mammals. These analyses provide the first genomic scale structural detail of marsupial TCR genes, a lineage of mammals used as models of early development and human disease.