The Functional and Allometric Implications of Hipbone Trabecular Microarchitecture in a Sample of Eutherian and Metatherian Mammals

The pelvis plays an active role in weight bearing and countering the ground reaction forces incurred by the hindlimbs thus making it a critical component of the locomotor skeleton. Accordingly, this anatomical region is theoretically ideal for inferring locomotor behavior from both external skeletal morphology and trabecular microarchitecture, with the latter possibly offering nuanced insights into the mechanical loading environment given its increased plasticity and higher turnover rate. However, trabecular microarchitecture is also known to be influenced by a variety of factors including body size, sex, age, genetic regulation, diet and activity level, that collectively hinder the ability to generate consistent functional inferences. In this study, a comparative sample of mammals (42 species spanning four orders) of varying sizes, yet comparable locomotor repertoires, were evaluated to determine the effects of body size, phylogeny and locomotion on hipbone trabecular microarchitecture. This study found a weak functional signal detected in differences in bone volume fraction and the degree of anisotropy across certain pre-assigned locomotor categories, while confirming previously recognized allometric scaling trends reported for other mammalian samples based on the femur. Within primates, a more anisotropic pattern was observed for quadrupedal species attributed to their repetitive loading regimes and stereotypical limb excursions, while isotropic values were revealed for taxa utilizing more varied arboreal repertoires. Humans, despite a frequent and predictable loading environment associated with their use of bipedalism, showed relatively isotropic values. This study highlights the confounding factors that influence trabecular microarchitecture and consequently limit its utility as a method for investigating locomotor adaptation

The Upright Battle: Morphological Trends of the Bipedal Pelvis

The shift to bipedal locomotion is a distinguishing feature of the human lineage that required substantial remodeling of the postcranium in hominins. The pelvis, due to its important functional role as a stabilizing and weight-bearing structure, has undergone one of the most drastic transformations in the skeleton to accommodate obligate bipedalism, thus making it a valuable region for studying locomotor behavior within the fossil record. Although bipedalism occurs in several mammalian groups, it is rare within primates and the ability to utilize a striding gait with an erect, or orthograde, posture remains unique to hominins. Orthograde posture in this context is therefore an equally important consideration, as it reorients the trunk into a vertical stance that undoubtedly contributes to the specialized pelvic anatomy found in hominin taxa. Given that all extant hominoids partake in varying degrees of orthogrady, it is argued that this change in posture preceded, and possibly even preadapted hominoids for, the eventual shift to terrestrial bipedalism. Therefore, this dissertation seeks to isolate features relating explicitly to bipedality from those required for orthograde posture to aid in understanding the functional roles of both in the evolution of hominin bipedalism. This dissertation utilizes a comparative sample that consists of extant primates and non-primate bipedal mammals that differ in body size, yet converge on aspects of their locomotor and postural repertoires, providing a comprehensive assessment of pelvic skeletal anatomy that lends novel insights into the functional interpretations that can be derived from this region. Both the trabecular microarchitecture and the overall dimensions of the pelvis are considered collectively in a phylogenetic context to isolate morphology that is informative for accurate reconstruction of locomotor behavior. Building on these insights, the first finite element analysis (FEA) validation study is performed on a non-human primate pelvis using previously collected strain gauge data to establish accurate parameters that will enhance future modeling capabilities thereby refining methods available for inferring locomotor behavior within the fossil record. Results indicate a corroboration of functional skeletal attributes at different levels throughout the pelvis that accommodate loading sustained at the hip joint during locomotion. Findings are complementary in nature, suggesting a complex interplay between body size, phylogeny and function that reinforce the importance of using a holistic approach to adequately evaluate pelvic skeletal morphology. Additionally, finite element modeling demonstrates that the interaction between the external and internal skeletal attributes are important for recreating realistic strain environments within the pelvis. Validation of the primate pelvis FEA model was partially obtained as congruence at strain gauge sites was observed for several regions. However, the gauges near the loading surface and those surrounding the pubic symphysis were inaccurate regardless of modifications to boundary conditions. The phylogenetic modeling component of the study elicits better model fit when an Ornstein–Uhlenbeck approach is implemented and when acetabulum height is used as a predictor variable, thereby elucidating important relationships between pelvic traits and body size over time that can be used for evaluating pelvic morphology encountered in the fossil record

A mathematical model quantifies proliferation and motility effects of TGF--β\beta on cancer cells

Transforming growth factor (TGF) $\beta$ is known to have properties of both a tumor suppressor and a tumor promoter. While it inhibits cell proliferation, it also increases cell motility and decreases cell--cell adhesion. Coupling mathematical modeling and experiments, we investigate the growth and motility of oncogene--expressing human mammary epithelial cells under exposure to TGF--$\beta$. We use a version of the well--known Fisher--Kolmogorov equation, and prescribe a procedure for its parametrization. We quantify the simultaneous effects of TGF--$\beta$ to increase the tendency of individual cells and cell clusters to move randomly and to decrease overall population growth. We demonstrate that in experiments with TGF--$\beta$ treated cells \textit{in vitro}, TGF--$\beta$ increases cell motility by a factor of 2 and decreases cell proliferation by a factor of 1/2 in comparison with untreated cells.Comment: 15 pages, 4 figures; to appear in Computational and Mathematical Methods in Medicin

Sex classification using the human sacrum: Geometric morphometrics versus conventional approaches

The human pelvis shows marked sexual dimorphism that stems from the conflicting selective pressures of bipedal locomotion and parturition. The sacrum is thought to reflect this dimorphism as it makes up a significant portion of the pelvic girdle. However, reported sexual classification accuracies vary considerably depending on the method and reference sample (54%-98%). We aim to explore this inconsistency by quantifying sexual dimorphism and sex classification accuracies in a geographically heterogeneous sample by comparing 3D geometric morphometrics with the more commonly employed linear metric and qualitative assessments. Our sample included 164 modern humans from Africa, Europe, Asia, and America. The geometric morphometric analysis was based on 44 landmarks and 56 semilandmarks. Linear dimensions included sacral width, corpus depth and width, and the corresponding indices. The qualitative inspection relied on traditional macroscopic features such as proportions between the corpus of the first sacral vertebrae and the alae, and sagittal and coronal curvature of the sacrum. Classification accuracy was determined using linear discriminant function analysis for the entire sample and for the largest subsamples (i.e., Europeans and Africans). Male and female sacral shapes extensively overlapped in the geometric morphometric investigation, leading to a classification accuracy of 72%. Anteroposterior corpus depth was the most powerful discriminating linear parameter (83%), followed by the corpus-area index (78%). Qualitative inspection yielded lower accuracies (64–76%). Classification accuracy was higher for the Central European subsample and diminished with increasing geographical heterogeneity of the subgroups. Although the sacrum forms an integral part of the birth canal, our results suggest that its sex-related variation is surprisingly low. Morphological variation thus seems to be driven also by other factors, including body size, and sacrum shape is therefore likely under stronger biomechanical rather than obstetric selection

Author Correction: Dynamic finite-element simulations reveal early origin of complex human birth pattern

Human infants are born neurologically immature, potentially owing to conflicting selection pressures between bipedal locomotion and encephalization as suggested by the obstetrical dilemma hypothesis. Australopithecines are ideal for investigating this trade-off, having a bipedally adapted pelvis, yet relatively small brains. Our finite-element birth simulations indicate that rotational birth cannot be inferred from bony morphology alone. Based on a range of pelvic reconstructions and fetal head sizes, our simulations further imply that australopithecines, like humans, gave birth to immature, secondary altricial newborns with head sizes smaller than those predicted for non-human primates of the same body size especially when soft tissue thickness is adequately approximated. We conclude that australopithecines required cooperative breeding to care for their secondary altricial infants. These prerequisites for advanced cognitive development therefore seem to have been corollary to skeletal adaptations for bipedal locomotion that preceded the appearance of the genus Homo and the increase in encephalization

Dynamic finite-element simulations reveal early origin of complex human birth pattern

Human infants are born neurologically immature, potentially owing to conflicting selection pressures between bipedal locomotion and encephalization as suggested by the obstetrical dilemma hypothesis. Australopithecines are ideal for investigating this trade-off, having a bipedally adapted pelvis, yet relatively small brains. Our finite-element birth simulations indicate that rotational birth cannot be inferred from bony morphology alone. Based on a range of pelvic reconstructions and fetal head sizes, our simulations further imply that australopithecines, like humans, gave birth to immature, secondary altricial newborns with head sizes smaller than those predicted for non-human primates of the same body size especially when soft tissue thickness is adequately approximated. We conclude that australopithecines required cooperative breeding to care for their secondary altricial infants. These prerequisites for advanced cognitive development therefore seem to have been corollary to skeletal adaptations for bipedal locomotion that preceded the appearance of the genus Homo and the increase in encephalization

New insights on hip bone sexual dimorphism in adolescents and adults using deformation-based geometric morphometrics

Morphological variation of the human pelvis, and particularly the hip bone, mainly results from both female-specific selective pressure related to the give birth of large-headed newborns, and constraints in both sexes for efficient bipedal locomotion, abdominal stability, and adaptation to climate. Hip bone morphology has thus been extensively investigated using several approaches, although the nuances of inter-individual and sex-related variation are still underappreciated, and the effect of sex on ontogenetic patterns is debated. Here, we employ a landmark-free, deformation-based morphometric approach to explore variation in modern human hip bone shape and size from middle adolescence to adulthood. Virtual surface models of the hip bone were obtained from 147 modern human individuals (70 females and 77 males) including adolescents, and young and mature adults. The 3D meshes were registered by rotation, translation, and uniform scaling prior to analysis in Deformetrica. The orientation and amplitude of deviations of individual specimens relative to a global mean were assessed using Principal Component Analysis, while colour maps and vectors were employed for visualisation purposes. Deformation-based morphometrics is a time-efficient and objective method free of observer-dependent biases that allows accurate shape characterisation of general and more subtle morphological variation. Here, we captured nuanced hip bone morphology revealing ontogenetic trends and sex-based variation in arcuate line curvature, greater sciatic notch shape, pubic body and rami length, acetabular expansion, and height-to-width proportions of the ilium. The observed ontogenetic trends showed a higher degree of bone modelling of the lesser pelvis of adolescent females, while male variation was mainly confined to the greater pelvis

Support varieties for selfinjective algebras

Support varieties for any finite dimensional algebra over a field were introduced by Snashall-Solberg using graded subalgebras of the Hochschild cohomology. We mainly study these varieties for selfinjective algebras under appropriate finite generation hypotheses. Then many of the standard results from the theory of support varieties for finite groups generalize to this situation. In particular, the complexity of the module equals the dimension of its corresponding variety, all closed homogeneous varieties occur as the variety of some module, the variety of an indecomposable module is connected, periodic modules are lines and for symmetric algebras a generalization of Webb's theorem is true

Breast milk and in utero transmission of HIV-1 select for envelope variants with unique molecular signatures

Additional file 5: Figure S5. Representative CD4 infectivity curves using Affinofile cells for IUT (top) and BMT (bottom) maternal–infant pairs. Affinofile cells were induced to generate a 100-fold range of CD4 surface density (ABS/cell) and infected with 2000 IU pseudotyped virus. Percent infection was measured as the percent luciferase relative to infected and maximally induced Affinofile cells. Data shown are representative curves among 3–4 experimental replicates